ascorbic-acid and Colorectal-Neoplasms

Vitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers.. Ten genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables. Effect size estimates for the genetic associations of the vitamin C-associated genetic variants with six major malignancies of digestive system were obtained from the FinnGen (N = 309 154) and UK Biobank (N = 367 542) studies. Results from the two studies were combined using meta-analysis.. Genetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32-0.94; P = 0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73-0.96; P = 0.013) for colorectal cancer. There was a suggestive association between genetically predicted higher circulating vitamin C with lower risk of liver cancer in FinnGen but no association in the meta-analysis (odds ratio 0.69; 95% CI 0.36-1.32; P = 0.265). Genetically predicted circulating vitamin C was not associated with cancers of the esophagus, stomach, or pancreas.. This Mendelian randomization study indicates that vitamin C might play a role in the prevention of small intestine and colorectal cancer.

Topics: Ascorbic Acid; Colorectal Neoplasms; Digestive System Neoplasms; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Vitamins

The success of a colonoscopy is highly dependent on the quality of bowel preparation (BP). Many patients have poor BP due to non-compliance with regular instructions. Reports concerning the effects of enhanced instructions on BP quality are inconsistent. The aim of this meta-analysis was to compare BP quality between patients receiving enhanced instructions in addition to regular instructions and those who received regular instructions only.. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched to identify relevant studies published for August 2015. The quality of BP (adequate/inadequate), adenoma detection rate, polyp detection rate, willingness to repeat preparation, and adverse events were estimated by using odds ratios (OR) and 95% confidence intervals (CI) with random effects models.. Eight randomized controlled trials (n = 3795) were included. Patients who received enhanced instructions showed significantly better BP quality than those receiving only regular instructions (OR, 2.35; 95% CI, 1.65-3.35; P < .001). Subgroup analysis showed that the beneficial effects of enhanced instructions on BP quality were consistent among patients receiving different purgative types, administration methods, or diet restriction (all P < .05). Patients in the enhanced instructions group showed more willingness to repeat the preparation (OR, 1.91; 95% CI, 1.20-3.04; P = .006).. Enhanced instructions significantly improved the quality of BP and willingness to repeat the preparation in patients undergoing colonoscopy. Factors related to patient instructions appear to be as important as the preparation method itself in improving BP quality.

Topics: Adenoma; Ascorbic Acid; Cathartics; Cecum; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Diet; Early Detection of Cancer; Humans; Intubation, Gastrointestinal; Patient Compliance; Patient Education as Topic; Polyethylene Glycols; Randomized Controlled Trials as Topic

To comprehensively summarize the association between dietary intake of vitamins A, C, and E and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer, relevant studies were identified in MEDLINE and EMBASE up to 31 October 2012. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I statistics. A total of 13 studies with 3832 CRA cases were included in this meta-analysis. On the basis of the highest versus lowest analysis, dietary intake of vitamin C reduced the risk of CRA by 22% (SRRs 0.78, 95% CIs: 0.62-0.98). Subgroup analyses showed that this relation was not modified by BMI, smoking status, and dietary energy intake. Further, dietary intake of β-carotene was also inversely associated with the risk of CRA. However, dietary intake of vitamins A and E was not associated with the risk of CRA in overall and subgroup analyses (vitamin A: SRRs 0.87, 95% CIs: 0.67-1.14; vitamin E: SRRs 0.87, 95% CIs: 0.69-1.10). Our results indicate that dietary intake of vitamin C and β-carotene, but not vitamins A and E, could reduce the risk of CRA. However, these associations seem to be limited. Further investigation using large samples and a rigorous methodology is warranted.

Topics: Adenoma; Ascorbic Acid; Clinical Trials as Topic; Colorectal Neoplasms; Diet; Humans; Prognosis; Risk Factors; Vitamin A; Vitamin E

To determine whether medication interventions enhance the sensitivity and specificity of guaiac-based fecal occult blood testing (FOBT) when screening for colorectal cancer (CRC).. We searched PubMed-MEDLINE, CINAHL, and the Cochrane databases using the MeSH headings occult blood, feces/analysis, and guaiac/analysis, linking them to variations of anticoagulants, heparin, warfarin, iron, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel, cyclooxygenase-2 inhibitors, and ascorbic acid (vitamin C). Study selections were limited to English studies involving humans.. All resulting titles and abstracts were reviewed for studies that included manipulation of medications associated with guaiac-based FOBT. If the study's relevance was unclear from the abstract, the full article was reviewed. The search resulted in 31 pertinent studies.. No studies addressed the effects of medication interventions on the sensitivity or specificity of FOBT screening. Randomized controlled trials, however, showed no increase in the rate of positive results among those taking NSAIDs. The literature is mixed regarding the effect of NSAIDs on the positive predictive value of a positive FOBT result, although no change in positive predictive value has been shown for warfarin. Iron will not affect FOBT results in vivo. Ascorbic acid might inhibit positive FOBT results both in vitro and in vivo, but it has not been studied in screening populations.. Studies evaluating the effects of medication intervention on FOBT screening for CRC are limited by their lower quality and because they do not address sensitivity and specificity. Available evidence, however, does not suggest a benefit from withholding NSAIDs, anticoagulant medications, or iron during the screening period. These recommendations should be abandoned in order to maximize adherence to screening. Positive FOBT results obtained among patients taking these medications deserve full evaluation for CRC. Until further studies clarify the effect of ascorbic acid on FOBT screening, withholding this medication before testing seems prudent.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Colorectal Neoplasms; Early Detection of Cancer; False Positive Reactions; Guaiac; Hematologic Agents; Humans; Indicators and Reagents; Iron; Occult Blood; Pharmaceutical Preparations; Predictive Value of Tests; Trace Elements; Vitamins; Withholding Treatment

Antioxidants, such as vitamin A, C and E, selenium and β-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population.. A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed.. Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus β-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos.. The review demonstrates that antioxidants (vitamin A, C and E, selenium and β-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer.

Topics: Adenoma; Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Humans; Selenium; Vitamin A; Vitamin E

Colorectal cancer is the third most incident cancer in the United States and is second only to lung cancer as a cause of cancer-related mortality. Colorectal cancer develops through a multistep process characterized by histopathological precursor lesions and molecular genetic alterations. This sequential process of tumorigenesis provides opportunities for the development and testing of both primary and secondary prevention strategies. This review focuses on chemoprevention, which is defined as the use of natural or synthetic agents to reverse the process of carcinogenesis. Epidemiological studies have consistently shown that chronic intake of nonsteroidal anti-inflammatory drugs (NSAIDs), principally aspirin, can reduce the incidence of colorectal adenomas and carcinomas. Evaluation of NSAIDs, including newer selective cyclo-oxygenase-2 inhibitors, in carcinogen-induced and genetically manipulated animal models of colorectal cancer demonstrates that these drugs are effective chemopreventive agents. In humans, the NSAID sulindac has been studied in familial adenomatous polyposis patients and was found to regress colorectal adenomas in a placebo-controlled trial. More recently, the selective cyclo-oxygenase-2 inhibitor Celebrex was also shown to be effective in familial adenomatous polyposis and was approved by the Food and Drug Administration as a adjuct to usual care in these patients. NSAIDs, as well as other chemopreventive agents, are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcome of these studies has the potential to impact patient management practices. However, chemopreventive agents cannot be recommeded at present for average-risk individuals or for those with sporadic colorectal neoplasia. In addition to demonstrating efficacy, chemopreventive agents must be safe and well tolerated for chronic administration and should be relatively cost-effective. Although still in its infancy, the field of chemoprevention is an exciting and rapidly advancing area of investigation. Chemopreventive strategies, if effective, offer the promise of producing a paradigm shift in our current approach to colorectal cancer.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; beta Carotene; Calcium Compounds; Colorectal Neoplasms; Dietary Fiber; Dietary Supplements; Eflornithine; Enzyme Inhibitors; Female; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Prognosis; Risk Assessment; Sensitivity and Specificity; Ursodeoxycholic Acid; Vitamin E

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Ascorbic Acid; Calcium, Dietary; Colorectal Neoplasms; Dietary Fats; Dietary Fiber; Humans; Research

Epidemiologic studies of the relationship of diet to cancer etiology are hampered by methodologic difficulties which can be overcome by careful trial design. The use of appropriate dietary assessment instruments is necessary to minimize bias and improve accuracy of diet assessment. Population studies implicate dietary fat intake in the etiology of colorectal carcinogenesis, and the incidence of colorectal malignancies around the world is positively correlated with meat and fat consumption and total calorie intake. Retrospective studies of fat intake yield equivocal results, whereas prospective studies have failed to show a relationship between fat intake and colon cancer risk. An inverse relationship exists between fiber consumption and colorectal cancer incidence and mortality rates. The positive observational studies are supported by laboratory studies of experimental carcinogenesis which show a greater number of tumors in animals fed high-fat or high-calorie diets. Increased fiber intake appears to offer some protection against colorectal cancer. Plausible mechanisms have been proposed in animals for the role of fat and fiber in colorectal carcinogenesis; the mechanisms in human populations await further description. The interrelationships between fat consumption and consumption of dietary fiber and micronutrients have made it difficult to assess the roles of these substances in the etiology of colorectal cancer. Calcium offers protection in animal systems, and the data in humans are suggestive but not yet conclusive. Data on the role of alcohol in colorectal carcinogenesis remain inconclusive. Little evidence exists for a protective effect of retinoids and carotenoids; the evidence for selenium and vitamin C is limited and evolving.

Topics: Adult; Animals; Ascorbic Acid; Calcium, Dietary; Cholesterol, Dietary; Colonic Neoplasms; Colorectal Neoplasms; Diet; Diet Surveys; Dietary Fats; Dietary Fiber; Energy Intake; Epidemiologic Methods; Ethanol; Female; Humans; Male; Middle Aged; Rats; Risk Factors; Selenium; Vitamin A

A hyperosmolar ascorbic acid-enriched polyethylene glycol-electrolyte (ASC-PEG) lavage solution ensures excellent bowel preparation before colonoscopy; however, no study has demonstrated the efficacy of this lavage solution before surgery. This study aimed to establish the non-inferiority of ASC-PEG to the standard polyethylene glycol-electrolyte solution (PEG-ELS) in patients undergoing laparoscopic resection for colorectal cancer.. This was a prospective, single-blind, multicenter, randomized, controlled, non-inferiority clinical trial. Overall, 188 patients scheduled for laparoscopic colorectal resection for single colorectal adenocarcinomas were randomly assigned to undergo preparation with different PEG solutions between August 2017 and April 2020 at four hospitals in Japan. Participants received ASC-PEG (Group A) or PEG-ELS (Group B) preoperatively. The primary endpoint was the ratio of successful bowel preparations using the modified Aronchick scale, defined as "excellent" or "good.". After exclusion, 86 and 87 patients in Groups A and B, respectively, completed the study, and their data were analyzed. ASC-PEG was not inferior to PEG-ELS in terms of effective bowel preparation prior to laparoscopic colorectal resection (0.93 vs. 0.92; 95% confidence interval, - 0.078 to 0.099, p = 0.007). The total volume of cleansing solution intake was lower in Group A than in Group B (1757.0 vs. 1970.1 mL). Two and three severe postoperative adverse events occurred in Groups A and B, respectively. Patient tolerance of the two solutions was almost equal.. ASC-PEG is effective for preoperative bowel preparation in patients undergoing laparoscopic resection for colorectal cancer and is non-inferior to PEG-ELS.

Topics: Ascorbic Acid; Cathartics; Colonoscopy; Colorectal Neoplasms; Electrolytes; Humans; Polyethylene Glycols; Prospective Studies; Single-Blind Method; Therapeutic Irrigation

To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC).. Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription.. The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only.. High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Bevacizumab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Glucosephosphate Dehydrogenase; Humans; Leucovorin; Rectal Neoplasms

Colonoscopy requires bowel cleansing for gut mucosa visualization; high-quality cleansing facilitates lesion detection. NER1006 is a 1L polyethylene glycol (PEG) bowel preparation. This post hoc analysis of two randomized trials investigated cleansing efficacy assessed, as in clinical practice, by site endoscopists.. Patients received NER1006, 2L PEG + ascorbate (2LPEG), or oral sulfate solution (OSS) as a 2-day evening/morning regimen (N2D) or NER1006 morning-only dosing (N1D). Treatment-blinded site endoscopists assessed cleansing using the Harefield Cleansing Scale (HCS). Analyses were conducted in a modified full analysis set, including (mFAS; n = 1378) or excluding (mFAS2; n = 1319) imputed failures, and in patients with 100% treatment adherence (mFAS100; n = 1047). Overall cleansing success (HCS grade A/B), overall high-quality cleansing (HCS grade A), and high-quality segments (HCS 3-4) per treatment population were analyzed.. Overall cleansing success was higher with N2D than 2LPEG (92.7-97.5% vs. 87.9-93.0%), and more patients had overall high-quality cleansing with N2D and N1D than 2LPEG (68.0-72.1% and 64.0-68.4% vs. 50.7-56.0%). Without imputed failures, N2D delivered more overall high-quality cleansing than OSS (74.5-77.3% vs. 67.8-69.8%). More high-quality segments were demonstrated with N2D and N1D versus 2 LPEG (82.5-87.1% and 79.4-84.4% vs. 70.4-76.3%) and with N2D versus OSS (82.7-89.5% vs. 78.1-84.4%).. When assessed by site endoscopists, NER1006 delivers greater high-quality cleansing than 2LPEG or OSS.

Topics: Ascorbic Acid; Cathartics; Colon; Colonoscopy; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Polyethylene Glycols; Preoperative Care; Quality Improvement; Sulfates

Colonic bubbles obscure the colonic mucosa during colonoscopy following bowel preparation with polyethylene glycol plus ascorbic acid (PEG-Asc). Simethicone is used to enhance visualization during colonoscopy. We aimed to determine the optimal timing of simethicone addition to improve bowel preparation using PEG-Asc.. This prospective, randomized study enrolled patients undergoing elective colonoscopy from April 2017 to January 2018. They were randomly assigned to one of the following three groups: PEG-Asc only (control) or simethicone addition in the morning on the day of colonoscopy (PEG-S1) or in the evening of the day prior to colonoscopy (PEG-S2). The primary outcome was the quality of colon cleansing, and the secondary outcomes were the adenoma detection rate (ADR), polyp detection rate (PDR), and diminutive (≤ 5 mm) ADR.. In total, 240 patients were randomly allocated to the three groups; six patients were withdrawn. Of the 234 patients evaluated, 78, 79, and 77 were allocated to the control, PEG-S1, and PEG-S2 groups, respectively. The bubble scores of all colonic segments were lowest in the PEG-S2 group. There was no significant difference in ADR or PDR among the three groups. However, the diminutive ADR was significantly higher in the PEG-S2 group compared to the other two groups (control 5.1% vs. PEG-S1 8.9% vs. PEG-S2 20.8%; P = 0.009).. Addition of simethicone to PEG-Asc at the optimal time prevents the formation of air bubbles and so improves the quality of bowel preparation, especially enhancing diminutive ADR.

Topics: Adenoma; Adult; Aged; Antifoaming Agents; Ascorbic Acid; Cathartics; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Polyethylene Glycols; Prospective Studies; Simethicone

Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC).. In the dose-escalation phase, patients received AA (0.2-1.5 g/kg, 3-h infusion, once daily, days 1-3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed.. Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1-3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3-4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF.. The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC.. ClinicalTrial.gov Identifier: NCT02969681 .

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Asian People; Colorectal Neoplasms; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Stomach Neoplasms

Inadequate bowel cleansing is a major burden for endoscopy units. The aim of this study was to compare two intensive bowel cleansing regimens in patients with previous colonoscopy with inadequate bowel preparation.. Patients with inadequate cleansing at index colonoscopy were randomized to 4-L split-dose polyethylene-glycol (PEG) regimen vs. 2-L split-dose PEG plus ascorbic acid (PEG+Asc) regimen. All individuals underwent a 3-day low-residue diet and received 10 mg of bisacodyl, the day before colonoscopy. Cleansing was considered to be adequate if the Boston Bowel Preparation Scale scored ≥2 at each colonic segment. A non-inferiority analysis was performed to demonstrate that colonic cleansing with 2-L PEG+Asc was not inferior to 4-l PEG, considering a non-inferiority margin of 10%.. Adequate bowel cleansing was significantly higher in patients assigned to 4-L PEG regimen (n=127) vs. those randomized to 2-L PEG+Asc regimen (n=129) by intention-to-treat analysis (81.1 vs. 67.4%, odds ratio (OR) 2.07, 95% confidence interval (CI) (1.163-3.689)) and by per-protocol analysis (86.6 vs. 71.7%, OR: 2.55, 95% CI: (1.316-4.922)). The study was terminated for futility after the interim analysis, because the 95% CI of the difference of proportions was 3.13-24.27% in the intention-to-treat analysis and 3.33-26.47% in the per-protocol analysis, confirming the superiority of 4-L PEG preparation.. After 3-day low-residue diet and oral bisacodyl before colonoscopy, colon cleansing with 4-L split-dose PEG was superior to 2-L split-dose PEG+Asc in patients with previous inadequate cleansing. (EUDRACT: 2013-002506-31, NCT02073552).

Topics: Adenoma; Aged; Ascorbic Acid; Bisacodyl; Cathartics; Cecum; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Dietary Fiber; Early Termination of Clinical Trials; Female; Humans; Intention to Treat Analysis; Intubation, Gastrointestinal; Male; Middle Aged; Nausea; Polyethylene Glycols; Vitamins

This study aimed to investigate the clinical utility of a prepackaged low-residue diet (PLD) compared with a restricted diet (RD) for colonoscopic bowel preparation.. A prospective randomized controlled trial was carried out with patients undergoing colonoscopy. One hundred patients were randomly assigned to PLD and RD groups. In the RD group, the patients received an information sheet containing acceptable low-residue options and instructions from the medical staff. All patients received 10 ml sodium picosulphate the day before colonoscopy and 1 l of polyethylene glycol with ascorbic acid (PEG-A) on the day of the colonoscopy. If the bowel preparation was not adequate, an additional PEG-A solution was given. The primary outcome was the efficacy of colonic cleansing as rated by the Boston Bowel Preparation Scale (BBPS). The additional amount of PEG-A solution, adenoma detection rate and patient tolerance were assessed as secondary outcomes.. The BBPS score in the PLD group was 7.3 ± 1.7 compared with 6.5 ± 1.7 in the RD group. The quality of bowel preparation was significantly better in the PLD group (P < 0.05). The mean amount of additional PEG-A solution in the PLD group was smaller than in the RD group (293.8 ± 474.8 vs 444.1 ± 625.0 ml), but there was no statistical difference between the two groups. Adenoma detection rates and patient tolerance were similar in the two groups.. Prepackaged low-residue diets PLD is superior to RD for bowel preparation for colonoscopy.

Topics: Adenoma; Aged; Ascorbic Acid; Cathartics; Citrates; Colonoscopy; Colorectal Neoplasms; Diet; Female; Humans; Male; Middle Aged; Organometallic Compounds; Picolines; Polyethylene Glycols; Preoperative Care

Conventional bowel cleansers for colonoscopy have an unpleasant taste and a large volume of solution must be ingested. Coffee increases bowel motility and has an intense flavor. The addition of coffee to a polyethylene glycol+ascorbic acid solution reduces the volume of the solution to be consumed without reducing efficacy, improves the taste of the solution and enhances patient comfort.. Outpatients with clinical indication or people who wanted screening for cancer were considered eligible. Control group (PEGAS group) consumed a 1-L solution of polyethylene glycol+ascorbic acid twice. Study group (COF group) consumed 750 mL of coffee+polyethylene glycol+ascorbic acid twice. Bowel cleansing was rated using the Aronchick, Ottawa scale, polyp detection rate and colonoscopic insertion time. Tolerability, acceptability, preference, and adverse events were investigated by questionnaires.. The COF group had non-inferiority in efficacy (non-inferiority margin, -15%; lower limit of 95% confidence interval for difference between success rates, -4.7% and -8.4% from both scales, respectively). Polyp detection rates were 0.48 and 0.60, respectively (P=0.067). Colonoscopic insertion times were 323.6+/-166.8 s and 330.7+/-243.6 s, respectively (P=0.831). Significant improvement was observed with respect to ease of drinking (P=0.012), taste (P=0.026) and preference (P=0.046) in the COF group. Adverse events occurred in 52.4% and 60.4% in the two groups, respectively (P = 0.251).. The addition of coffee to polyethylene glycol+ascorbic acid solution reduces the required volume for bowel preparation without reduced efficacy and enhances patient comfort in coffee-drinkers.

Topics: Administration, Oral; Adult; Aged; Ascorbic Acid; Cathartics; Coffee; Colonoscopy; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Patient Compliance; Patient Preference; Polyethylene Glycols; Prospective Studies; Republic of Korea; Single-Blind Method; Surveys and Questionnaires; Taste; Therapeutic Irrigation; Treatment Outcome; Young Adult

The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening.. To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy.. Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale.. A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses.. In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.

Topics: Aged; Ascorbic Acid; Cathartics; Citrates; Citric Acid; Colonoscopy; Colorectal Neoplasms; Defecation; Dizziness; Drug Administration Schedule; Early Detection of Cancer; Female; Humans; Male; Middle Aged; Nausea; Organometallic Compounds; Pain; Patient Acceptance of Health Care; Picolines; Polyethylene Glycols; Prospective Studies; Surveys and Questionnaires; Vomiting

It has long been a matter of interest whether antioxidant vitamins are protective against colorectal cancer as well as human cancers in general, but epidemiological evidence is inconclusive. We investigated associations of dietary intakes of retinol and antioxidant vitamins with colorectal cancer risk in 816 incident cases of histologically confirmed colorectal cancer and 815 controls randomly selected for the Fukuoka colorectal cancer study in Japan. Dietary intakes were assessed by a PC-assisted interview regarding 148 food items. Statistical adjustment was made for body mass index, physical activity, calcium, and n-3 fatty acid intake and other factors. Retinol intake was significantly, inversely associated with colorectal cancer risk; the odds ratio for the highest vs. lowest was 0.55 (95% CI: 0.35, 0.88; P (trend) = 0.01) in women, but a modest increase in the risk was observed among men with the highest intake of retinol. Liver was the major source of retinol intake and showed similar associations with colorectal cancer risk in men and women. Intake of carotenes, vitamin C, and vitamin E were not related to colorectal cancer risk in either men or women. The study did not support a hypothesis that dietary intake of antioxidant vitamins is protective in the development of colorectal cancer.

Topics: Aged; Antioxidants; Ascorbic Acid; Carotenoids; Colorectal Neoplasms; Diet; Fatty Acids, Omega-3; Female; Humans; Japan; Male; Middle Aged; Odds Ratio; Vitamin A; Vitamin E

To investigate the effectiveness of low-volume plus ascorbic acid [polyethylene glycol plus ascorbic acid (PEG + Asc)] and high-volume plus simethicone [polyethylene glycol plus simethicone (PEG + Sim)] bowel preparations.. A total of one hundred and forty-four outpatients (76 males), aged from 20 to 84 years (median age 59.5 years), who attended our Department, were divided into two groups, age and sex matched, and underwent colonoscopy. Two questionnaires, one for patients reporting acceptability and the other for endoscopists evaluating bowel cleansing effectiveness according to validated scales, were completed. Indications, timing of examination and endoscopical findings were recorded. Biopsy forceps were used as a measuring tool in order to determine polyp endoscopic size estimation. Difficulty in completing the preparation was rated in a 5-point Likert scale (1 = easy to 5 = unable). Adverse experiences (fullness, cramps, nausea, vomiting, abdominal pain, headache and insomnia), number of evacuations and types of activities performed during preparation (walking or resting in bed) were also investigated.. Seventy-two patients were selected for each group. The two groups were age and sex matched as well as being comparable in terms of medical history and drug therapies taken. Fourteen patients dropped out from the trial because they did not complete the preparation procedure. Ratings of global bowel cleansing examinations were considered to be adequate in 91% of PEG + Asc and 88% of PEG + Sim patients. Residual Stool Score indicated similar levels of amount and consistency of residual stool; there was a significant difference in the percentage of bowel wall visualization in favour of PEG + Sim patients. In the PEG + Sim group, 12 adenomas ≤ 10 mm diameter (5/left colon + 7/right colon) vs 9 (8/left colon + 1/right colon) in the PEG + Asc group were diagnosed. Visualization of small lesions seems to be one of the primary advantages of the PEG + Sim preparation.. PEG + Asc is a good alternative solution as a bowel preparation but more improvements are necessary in order to achieve the target of a perfect preparation.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Cathartics; Colonoscopy; Colorectal Neoplasms; Emollients; Humans; Male; Middle Aged; Pharmaceutical Solutions; Polyethylene Glycols; Simethicone; Surveys and Questionnaires; Therapeutic Irrigation; Young Adult

Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk, but these studies produced inconsistent results. In this pilot, randomized, double-blind, placebo-controlled clinical trial (n = 47), we assessed the effects of an antioxidant micronutrient combination (800 mg dl-alpha-tocopherol acetate, 24 mg beta-carotene, 1.0 g vitamin C, 200 microg l-selenomethionine, 7.2 mg riboflavin, 80 mg niacin, 60 mg zinc, 5 mg manganese) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and F2-isoprostane concentrations were measured using ELISAs, and cystine (CySS) was measured using high-performance liquid chromatography. Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group (P = 0.002), and CySS decreased by 19% (P = 0.03); however, interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers, although these findings were not statistically significant. The decreases of TNF-alpha and CySS were more pronounced in nonsmokers. These data suggest that (a) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and (b) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status.

Topics: Adenoma; Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Cystine; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; F2-Isoprostanes; Female; Humans; Interleukin-6; Male; Manganese; Micronutrients; Middle Aged; Niacin; Oxidative Stress; Pilot Projects; Riboflavin; Selenomethionine; Tumor Necrosis Factor-alpha; Vitamin E; Zinc

Arsenic trioxide (As2O3) has demonstrated effectiveness in treating acute promyelocytic leukemia (APL). Therefore the FDA has approved it to treat APL. In patients with refractory metastatic colorectal carcinoma (CRC), we assessed the efficacy and toxicity of As2O3/AA (ascorbic acid) as the outcome of this trial. Five patients with refractory metastatic CRC who failed all previous standard chemotherapy were enrolled in this study. They were treated with 0.25 mg/kg body weight/day As2O3 and 1000 mg/day of ascorbic acid for 5 days a week for 5 weeks. Each treatment cycle extended for 7 weeks with 5 weeks of treatment and 2 weeks of rest. All the patients developed moderate to severe toxic side effects to arsenic trioxide/AA therapy and therefore the study was discontinued. No CR (complete remission) or PR (partial remission) was observed. CT scans demonstrated stable or progressive disease. Three of the five patients died within 2 to 5 months after cessation of the therapy. None of the deaths could be related to this clinical trial. Two years of follow-up study showed that two patients were alive with stable disease. Under the current treatment regimen all patients developed moderate to severe side effects with no clinically measurable activity. As an alternate, efforts may be made to reduce the dose and arsenic trioxide may be combined with other standard regimen in reversing the chemo resistance.

Topics: Adult; Aged; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Colorectal Neoplasms; DNA Primers; Gene Expression Regulation; Humans; Middle Aged; Neoplasm Metastasis; Oxides; Thymidylate Synthase; Tomography, X-Ray Computed; Treatment Outcome

This clinical study compared the dynamics of antioxidants levels in patients with acute pancreatitis (AP), patients operated for colorectal cancer (CA), and healthy control subjects.. This prospective descriptive study enrolled 21 AP and 14 CA patients and 17 healthy controls. Blood was collected from AP patients on days 1, 5, and 9 and from CA patients before surgery and on days 1, 5, and 9 after surgery. We measured concentrations of selenium in plasma, red blood cells (RBCs), and big-toe nails, vitamin A (retinol) in serum, alpha-tocopherol in serum and in RBCs, vitamin C in serum, concentration ratio of 9,11- and 10,12-octadecanoic acids to linoleic acid in RBC membrane, activity of superoxide dismutase, and glutathione peroxidase in RBCs.. Plasma concentrations of selenium, vitamin A, and vitamin C were significantly lower in AP and CA patients than in healthy controls over the monitored period (P < 0.05). Patients with severe AP had a significantly lower concentration of selenium in RBCs than did healthy controls and CA patients (P < 0.05). The concentration of selenium in toe nails of AP patients was significantly lower than that in CA patients and healthy controls (P < 0.001). The marker of increased reactive oxygen species activity the ratio of 9,11- and 10,12-octadecanoic acids to linoleic acid in RBCs was significantly higher in AP and CA patients than in healthy controls (P < 0.05).. Low levels of measured antioxidants and increased activity of reactive oxygen species occurred during the course of AP. These findings applied in particular to patients who had severe AP. Levels of measured antioxidants seemed to be similar in AP and CA patients except for lower levels of selenium in toe nails in AP patients and lower selenium concentrations in RBCs in patients with severe AP.

Topics: Acute Disease; Acute-Phase Reaction; Adult; Aged; Antioxidants; Ascorbic Acid; Biomarkers; Colorectal Neoplasms; Erythrocytes; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Nails; Pancreatitis; Prospective Studies; Reactive Oxygen Species; Selenium; Superoxide Dismutase; Vitamin A

Calcium and antioxidant vitamins, such as A, C, and E, have been shown to reduce colorectal epithelial proliferation and thereby to act as possible chemoprotective agents in colorectal cancer. We investigated the effects of an intervention with calcium and vitamins on cell proliferation in the colonic mucosa of patients operated on for colorectal cancer. Patients with resected colorectal cancer Dukes' stage B-C were randomized to receive daily 30,000 IU of axerophthol palmitate (vitamin A) plus 1 g ascorbic acid (vitamin C) plus 70 mg of dl-alpha-tocopherol acetate (vitamin E) and 2 g natural calcium daily or indistinguishable placebo for 6 months. At the time of surgery and after 6 and 12 months of treatment, cell kinetics of normal colonic mucosa were assessed by using proliferating cell nuclear antigen (PCNA). Ninety patients were enrolled and 77 were assessable: 34 in the treatment group and 43 in the placebo group. A significant reduction of mean total PCNA labeling index (PCNALI) was evident in both groups after 6 months (vitamins/calcium, from 16.11 +/- 2.43 to 10.71 +/- 2.81; placebo, from 17.30 +/- 2.63 to 12.53 +/- 3.40). The difference in the percentage of reduction of mean PCNALI between baseline and after 6 months was not statistically significant in the treatment and placebo groups: 34% and 28%, respectively. A second control, 6 months after discontinuation of vitamin and calcium supplementation, showed a further decrease of mean total PCNALI in both groups, but this was not statistically significant. Our randomized trial showed that calcium and vitamin supplementation does not reduce cell kinetics of colon epithelium. Furthermore, this study suggests the need for extreme caution in the interpretation and publication of studies on chemoprotectants in colon cancer without a control group.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Calcium; Cell Division; Chemoprevention; Colorectal Neoplasms; Double-Blind Method; Female; Humans; Intestinal Mucosa; Kinetics; Male; Middle Aged; Vitamin A; Vitamin E

Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies.. In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 microg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of < 10 mm at enrollment or follow-up were left unresected until the end of the study.. 87-91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3-2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of < 5 or 5-9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26-4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication.. The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.

Topics: Adenoma; Aged; Antioxidants; Ascorbic Acid; Calcium, Dietary; Cell Division; Colonic Polyps; Colorectal Neoplasms; Constipation; Diarrhea; Diet; Double-Blind Method; Dyspepsia; Energy Intake; Female; Follow-Up Studies; Gastrointestinal Diseases; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Patient Compliance; Patient Dropouts; Prospective Studies; Time Factors; Vitamin A

Chemoprevention can be defined as an attempt at cancer control in which the occurrence of the disease is prevented by the administration of one (or more) chemical compounds. Main problems in chemoprevention studies are the choice of a suitable drug, the choice of an appropriate intermediate or definitive end point, and the definition of the population which should be investigated. Main classes of chemopreventive agents include vitamins, non-steroid antinflammatory drugs, minerals such as calcium or selenium, and other antioxidants such as N-acetylcysteine. Chemoprevention is particularly appealing in colorectal cancer, either because these lesions develop through a multistep process, or owing to the concept of "field carcinogenesis'. Between 1985 and 1990 we carried out a controlled study in which antioxidant vitamins or lactulose were used in an attempt to prevent the recurrence of colorectal polyps after their endoscopic removal. Among the 209 patients who could be evaluated, polyps recurred in 5.7% of the individuals who were given vitamins (A, C and E), 14.7% of patients given lactulose and 35.9% of untreated controls (chi 2 = 17.1, P < 0.001). The study suggested that either antioxidant vitamins or lactulose could be effective in reducing the recurrence rate of adenomatous polyps. In a subsequent on-going study, lower doses of the same vitamins were tested versus N-acetylcysteine (600 mg/day) or no treatment. Preliminary results showed a 40% reduction of the recurrence of polyps (versus controls) in individuals given N-acetylcysteine, while the effect of lower doses of vitamins was less appreciable. Definitive results of the study should be available by the end of 1998.

Topics: Acetylcysteine; Adenomatous Polyps; Ascorbic Acid; Chemoprevention; Colorectal Neoplasms; Gastrointestinal Agents; Humans; Lactulose; Neoplasm Recurrence, Local; Vitamin A; Vitamin E

People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer.. We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo; beta carotene (25 mg daily); vitamin C (1 g daily) and vitamin E (400 mg daily); or the beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations.. Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location.. The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.

Topics: Adenomatous Polyps; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Colonic Polyps; Colorectal Neoplasms; Confidence Intervals; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk; Vitamin E; Vitamins

Studies suggest that cell proliferation abnormalities of the colorectal mucosa are associated with risk of neoplasia, and most cancers of the large bowel are thought to arise from adenomas. The results of other studies suggest that vitamins A, C, and E have chemopreventive efficacy against colon cancer in animal models. This study evaluates the effect of dietary vitamin supplementation on cell kinetics in uninvolved rectal mucosa in patients with colorectal adenomas. Twenty patients with colorectal adenomas were given vitamins A, C, and E for 6 months after complete polypectomy, and 21 patients with adenomas received placebo. In each patient, six biopsy specimens were taken from normal-appearing rectal mucosa before treatment and after 3 and 6 months of treatment and were incubated with tritiated thymidine ([3H]thymidine), and the [3H]thymidine-labeled cells were counted by use of autoradiography. Two parameters of cell proliferation were evaluated: 1) the ratio of the number of labeled cells to the total number of cells (thymidine labeling index) and 2) the ratio of the number of labeled cells in the upper 40% of the crypt to the total number of labeled cells in the crypt (phi h). The latter index reflects abnormal expansion of the proliferative compartment and is thought to be an intermediate biomarker of cancer risk. In patients receiving vitamins, phi h decreased progressively from baseline values, with increasing statistical significance (P less than .05 after 3 months, P less than .01 after 6 months). There was a statistically significant decrease in the thymidine labeling index in the 40% of the crypt near the mucosal surface, but the variation in the overall labeling index was not statistically significant. In the placebo group, we observed no statistically significant change in cell kinetics. These findings suggest that vitamin A, C, and E supplementation is effective in reducing abnormalities in cell kinetics that may indicate a precancerous condition. Before larger trials on chemoprevention of colorectal adenoma recurrence are conducted, additional studies are needed (a) to validate that cell kinetics is an intermediate biomarker, (b) to determine active agents, optimal dosage, and the relative efficacy of agents given alone and in combination, and (c) to test toxicity.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Anticarcinogenic Agents; Ascorbic Acid; Cell Division; Colorectal Neoplasms; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Rectum; Vitamin A; Vitamin E; Vitamins

Various volumes of bowel preparation are used in clinical practice. There is conflicting data on the effectiveness of individual regimens. This study aims to evaluate the efficacy and compliance of currently used bowel preparations with the European Society of Gastrointestinal Endoscopy (ESGE) performance measures using data of the Dutch nationwide colorectal cancer screening (CRC) program.. In a prospective, multicenter endoscopy database, we identified all CRC screening colonoscopies performed in 15 Dutch endoscopy centers from 2016 to 2020. We excluded procedures without documented bowel preparation or the Boston Bowel Preparation Scale (BBPS) score. Bowel preparation regimens were categorized into three groups, that is, 4-L (polyethylene glycol (PEG)), 2-L (2-L PEG with ascorbic acid) and ≤1-L volumes (sodium picosulfate with magnesium citrate, 1L-PEG with sodium sulfate and ascorbic acid or oral sulfate solution). European Society of Gastrointestinal Endoscopy performance measures included adequate BBPS score (≥6) (>90%), cecal intubation rate (CIR, >90%), adenoma detection rate (ADR, >25%) and polyp detection rate (PDR, >40%). Logistic regression was performed to identify predictive factors for adequate BBPS and patient discomfort.. A total of 39,042 CRC screening colonoscopies were included. Boston Bowel Preparation Scale scores, CIR, ADR and PDR for 4L, 2L and ≤1L regimens all met the minimum ESGE performance measures standards. However, an adequate BBPS score was more frequently seen with 2L regimens (98.0%) as compared to 4L (97.1%) and ≤1L regimens (97.0%) (p < 0.001), respectively. In addition, CIR was higher for ≤1L (98.4%) versus 4L (97.7%) and 2L (97.9%) regimens (p = 0.001), ADR higher for lower volume (≤1L (60.0%) and 2L (61.2)) versus higher volume (4L (58.6%)) regimens (p < 0.001), and PDR higher for ≤1L (70.0%) and 2L (70.8%) versus 4L (67.2%) regimens (p < 0.001). Boston Bowel Preparation Scale for ≤1L regimens was higher when combined with bisacodyl (97.3%) than without (95.6%) (p < 0.001). Overall, bisacodyl use was independently associated with higher patient discomfort (odds ratios = 1.47, confidence intervals = 1.26-1.72).. Despite variations in bowel preparation volumes, all regimens meet the minimum ESGE performance measures for bowel preparation and other quality parameters. Boston Bowel Preparation Scale can be further improved if ultra low volume regimens are combined with bisacodyl. The choice for either bowel preparation volume can therefore be based on volume-tolerance and patient preference.

Topics: Ascorbic Acid; Bisacodyl; Cathartics; Cecum; Colonoscopy; Colorectal Neoplasms; Early Detection of Cancer; Humans; Polyethylene Glycols; Prospective Studies

Malnutrition caused by insufficient nutritional supply may significantly hinder the quality of life among cancer patients. Sugar provides energy and nutritional support, but it also promotes cancer growth. Warburg effect is the reprogrammed glucose metabolic mode of cancer cells that meets the intensified ATP demand and biosynthesis. Vitamin C (VC) has anti-tumor effect. However, the relationship between cytotoxicity of VC on cancer cells and Warburg effect remains elusive, the effect of VC on glucose-induced oncogenic effect is also unclear. Based on colorectal cancer cell HCT116, our finding revealed that the discrepant oncogenic effect of different sugar is closely related to the intensification of Warburg effect, with glucose being the potent oncogenic component. Notably, as a potential Warburg effect inhibitor, VC suppressed cancer growth in a concentration-dependent manner and further reversed the glucose-induced oncogenic effect. Furthermore, VC protected tumor-bearing mice from insulin sensitivity impairment and inflammatory imbalance. These findings imply that VC might be a useful adjuvant treatment for cancer patients seeking to optimize nutritional support.

Topics: Animals; Ascorbic Acid; Colorectal Neoplasms; Glucose; Malnutrition; Mice; Quality of Life

Colorectal cancer (CRC) is strongly associated with altered cadherin adhesion molecules. Oxaliplatin is a standard treatment for CRC, yet high-doses have concerning side effects. In this study, the effects of oxaliplatin and the combination of oxaliplatin with vitamin C on HCT-116 CRC cell migration and invasion were studied through the roles of cellular oxidative stress associated with cadherin molecules.. The cellular assays used in this research were MTT, DCFH-DA, immunofluorescence, and western blotting. Cancer progression was examined using wound healing and Boyden chamber techniques.. The results indicate that hydrogen peroxide-induced cellular oxidative stress induced cancer cell migration and invasion. The combined treatment of oxaliplatin with a pro-oxidant concentration of vitamin C resulted in higher toxicity than treatment with oxaliplatin alone. However, treatment with the combination of oxaliplatin and antioxidant concentrations of vitamin C suppressed cancer migration and invasion. Furthermore, the combination treatment increased E-cadherin expression, whereas decreased that of N-cadherin.. Treatment with the combination of oxaliplatin with vitamin C can inhibit CRC cell growth and decrease cancer cell migration and invasion, via oxidative stress and cadherins.

Topics: Ascorbic Acid; Cadherins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Humans; Oxaliplatin; Oxidants

Colorectal cancer survivors often use multivitamins and other over-the-counter dietary supplements, but evidence is limited regarding their potential associations with mortality.. This prospective analysis included women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer-free at baseline (1992 or 1993) and diagnosed with colorectal cancer through June 2015. Detailed information on multivitamin use, vitamin C supplements, and vitamin E supplements was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 3176 and 2006 colorectal cancer survivors, respectively, among whom 2116 (648 from colorectal cancer) and 1256 (242 from colorectal cancer) died. Multivariable-adjusted Cox proportional hazards regression models examined associations. All statistical tests were 2-sided.. Among colorectal cancer survivors, 49.7% and 58.5% reported multivitamin use before and after diagnosis, respectively (vitamin C use before and after diagnosis: 27.8% and 28.1%; vitamin E use before and after diagnosis: 27.5% and 29.4%, respectively). There were no statistically significant associations of pre- or postdiagnosis multivitamin use with all-cause, colorectal cancer-specific, or noncolorectal cancer mortality. Vitamin C was also not associated with any mortality outcomes. However, prediagnosis vitamin E use was associated with a non-statistically significant increased risk of all-cause mortality (multivariable adjusted hazard ratio = 1.08, 95% confidence intervals = 0.96 to 1.23) and all other noncolorectal cancer mortality (multivariable adjusted hazard ratio = 1.13, 95% confidence intervals = 0.97 to 1.31).. These results suggest that multivitamin use before or after diagnosis is not associated with mortality in colorectal cancer survivors. However, vitamin E use may be associated with increased risk of mortality and merits further investigation.

Topics: Antioxidants; Ascorbic Acid; Colorectal Neoplasms; Female; Humans; Male; Vitamin E; Vitamins

Postoperative pain after colorectal cancer surgery has a significant impact on postoperative physical and mental health. Vitamin D deficiency has been correlated with both acute pain states, including postoperative and post-traumatic pain, and several chronic pain diseases. The effects of hypovitaminosis D on preoperative pain threshold and perioperative opioid use in colorectal cancer surgery still need to be studied.. To find the relationship between hypovitaminosis D on pain threshold, perioperative opioid use, and postoperative complications in colorectal cancer surgery.. A total of 112 patients, who were enrolled in this prospective, observational trial, were divided into 2 groups based on their preoperative serum 25-hydroxyvitamin D (25 [OH] D3) levels: (1) group D: vitamin D-deficient group (< 20 ng/mL); and (2) group S: vitamin D-sufficient group (>= 20 ng/mL).. Primary outcomes were pain threshold indexes, perioperative dosages of opioid use, and postoperative pain. Secondary outcomes were other postoperative complications.. Preoperative serum level of vitamin D was 14.94 ± 3.10 ng/mL in group D and 24.20 ± 4.80 ng/mL in group S. Significant differences were showed in the 3 indexes of pain threshold and analgesic consumption between the 2 groups (P < 0.05). A low 25 (OH) D3 level was associated with a higher opioid dose of sufentanil. There was an association between 25 (OH) D3 and pain enduring threshold (PET), beta coefficient beta = 0.532, 95% confidential interval  (0.440, 0.623), P < 0.001. The history of diabetes mellitus (DM) and vitamin C and vitamin D levels may be risk factors of surgical site infections (SSI), and the binary logistics regression model is statistically significant, chi-squared = 35.028, P < 0.001.. There is room for further expansion in the sample size. Our study lacked objective indicators to measure pain threshold. Intestinal recovery time and total hospital stay were not included in the final analysis. In the follow-up study, the vitamin D supplementation group should be set and the specific site of colorectal cancer surgery also needs to be divided more carefully.. On the basis of the study results, hypovitaminosis D is associated with increased perioperative opioid consumption in colorectal cancer surgery. Sensory perception and pain threshold of patients with insufficient 25 (OH) D3 concentration were more sensitive, and PET was lower. History of DM, vitamin D, and vitamin C may be factors related with SSI. Future studies are needed to investigate their relationship further and discover if postoperative pain and pain threshold can benefit from vitamin D supplementation in these patients.

Topics: Analgesics, Opioid; Ascorbic Acid; Calcifediol; Cohort Studies; Colorectal Neoplasms; Follow-Up Studies; Humans; Opioid-Related Disorders; Pain Threshold; Pain, Postoperative; Prospective Studies; Sufentanil; Vitamin D; Vitamin D Deficiency; Vitamins

The effectiveness of colonoscopy strictly depends on adequate bowel cleansing. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution (Plenvu; Norgine, Harefield, United Kingdom) has been introduced on the evidence of three phase-3 randomized controlled trials, but it had never been tested in the real-life.. To assess the effectiveness and tolerability of the 1 L preparation compared to 4 L and 2 L- PEG solutions in a real-life setting.. All patients undergoing a screening or diagnostic colonoscopy after a 4, 2 or 1 L PEG preparation, were consecutively enrolled in 5 Italian centers from September 2018 to February 2019. The primary endpoints of the study were the assessment of bowel cleansing success and high-quality cleansing of the right colon. The secondary endpoints were the evaluation of tolerability, adherence and safety of the different bowel preparations. Bowel cleansing was assessed through the Boston Bowel Preparation Scale. Adherence was defined as consumption of at least 75% of each dose, while tolerability was evaluated through a semi-quantitative scale. Safety was systematically monitored through adverse events reporting.. Overall, 1289 met the inclusion criteria and were enrolled in the study. Of these, 490 patients performed a 4 L-PEG preparation (Selgesse. This study supports the effectiveness and tolerability of 1 L PEG-ASC, also showing it is an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability.

Topics: Aged; Ascorbic Acid; Cathartics; Colon; Colonoscopy; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Italy; Male; Mass Screening; Medication Adherence; Middle Aged; Polyethylene Glycols; Prospective Studies; Treatment Outcome

A 58-year-old woman presented with a 1-week history of lower limb bruising. She had a medical history of recurrent metastatic colon cancer with a sigmoid colectomy and complete pelvic exenteration leading to colostomy and urostomy formation. She had malignant sacral mass encroaching on the spinal cord. This caused a left-sided foot drop for which she used an ankle-foot orthosis. She was on cetuximab and had received radiotherapy to the sacral mass 1 month ago. On examination, there were macular ecchymoses with petechiae on the lower limbs. There was sparing of areas that had been compressed by the ankle-foot orthosis. Bloods showed mild thrombocytopaenia and anaemia with markedly raised inflammatory markers. Coagulation studies consistent with inflammation rather than disseminated intravascular coagulation. She was found to have

Topics: Antineoplastic Agents, Immunological; Ascorbic Acid; Bacteremia; Colectomy; Colorectal Neoplasms; Diagnosis, Differential; Ecchymosis; Female; Humans; Klebsiella; Lower Extremity; Malnutrition; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Nutritional Support; Pelvic Exenteration; Scurvy; Skin; Treatment Outcome; Vitamins

The copper(ii) ion binding of the Ac-KGHGNG-NH2 and Ac-PTVHNE-NH2 fragments of FomA adhesin from Fusobacterium nucleatum was studied using potentiometry, UV-Vis, CD, EPR and DFT techniques. The coordination pattern was described in a wide range of pH values. Ligands begin interactions with metal ions using imidazole nitrogen. At pH 6.8 (a value typical of the large intestine environment), the metal ion was coordinated by the 3N donor atoms {Nim, 2 × N-amide} in both cases. However, the copper(ii) ion was bound more effectively by the Ac-PTVHNE-NH2 peptide. The formation of reactive oxygen species (ROS) was studied by UV-Vis and fluorescence spectroscopy, as well as gel electrophoresis in the presence of H2O2 and/or ascorbic acid. The complexes generated ROS in the highest amounts among all compounds. Moreover, they stimulated the CT26 cell line (mouse colon carcinoma) to produce ROS which lead to oxidative stress. It was also determined that such radicals took part in the plasmid degradation mechanism.

Topics: Amino Acid Sequence; Animals; Ascorbic Acid; Bacterial Outer Membrane Proteins; Cell Line, Tumor; Colorectal Neoplasms; Coordination Complexes; Copper; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Imidazoles; Ligands; Mice; Oxidative Stress; Peptide Fragments; Reactive Oxygen Species

A characteristic feature of malignant cells, such as colorectal cancer cells, is a profound decrease in the level of 5-hydroxymethylcytosine, a product of 5-methylcytosine oxidation by TET enzymes. Recent studies showed that ascorbate may upregulate the activity of TET enzymes in cultured cells and enhance formation of their products in genomic DNA.. The study included four groups of subjects: healthy controls (n = 79), patients with inflammatory bowel disease (IBD, n = 51), adenomatous polyps (n = 67) and colorectal cancer (n = 136). The list of analyzed parameters included (i) leukocyte levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine, a marker of oxidatively modified DNA, determined by means of isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry, (ii) expression of TET mRNA measured with RT-qPCR, and (iii) chromatographically-determined plasma concentrations of retinol, alpha-tocopherol and ascorbate.. Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine in DNA than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of ascorbate and retinol. A positive correlation was observed between plasma concentration of ascorbate and levels of two epigenetic modifications, 5-hydroxymethylcytosine and 5-hydroxymethyluracil in leukocyte DNA. Moreover, a significant difference was found in the levels of these modifications in patients whose plasma concentrations of ascorbate were below the lower and above the upper quartile for the control group.. These findings suggest that deficiency of ascorbate in the blood may be a marker of its shortage in other tissues, which in turn may correspond to deterioration of DNA methylation-demethylation. These observations may provide a rationale for further research on blood biomarkers of colorectal cancer development.

Topics: Adenoma; Aged; alpha-Tocopherol; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; DNA; Epigenesis, Genetic; Female; Humans; Inflammatory Bowel Diseases; Leukocytes; Male; Proto-Oncogene Proteins; RNA, Messenger; Vitamin A

Topics: Antineoplastic Agents; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Hormesis; Humans; Models, Biological; Reactive Oxygen Species; Sodium-Coupled Vitamin C Transporters

High-dose vitamin C administration has been reported to exhibit antitumor effect in various mouse models of cancer. However, the underlying mechanism of antitumor effect against colorectal cancer remains to be elucidated. In this study, we investigated the antitumor effect of high-dose vitamin C in a mouse model of chronic inflammation-associated colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). After cancer induction, the mice were administered vitamin C and/or irinotecan. Because irinotecan is a key drug in colorectal cancer treatment, it was used for comparison in this study. We examined reactive oxygen species (ROS) and interleukin-6 (IL-6) levels in the plasma of mice, as well as collagen type I and caspase-1 expression and neutrophil and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cell counts in the colon tissue. Vitamin C and/or irinotecan administration decreased the plasma level of ROS and IL-6 and increased the expression of collagen type I and caspase-1. Furthermore, it increased neutrophil and TUNEL-positive cell counts. The most significant changes in the parameters analyzed were observed when both vitamin C and irinotecan were administered.

Topics: Animals; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Azoxymethane; Colorectal Neoplasms; Dextran Sulfate; Dose-Response Relationship, Drug; Drug Synergism; Interleukin-6; Irinotecan; Male; Mice, Hairless; Reactive Oxygen Species

Liver metastatic disease is the main cause of death in colorectal cancer (CRC) patients. During metastatic spread of the disease an imbalance in the oxidative stress and inflammation plays a crucial role in tumor progression. In order to improve the efficacy of current therapies, new complementary therapeutic approaches are being analyzed including biologically active compounds with low side effects. The anti-inflammatory and anti-oxidant properties of Ocoxin® oral solution (OOS) prompt us to analyze its effect on the metastatic development of CRC to the liver. First, in vitro effect of OOS in tumor cell viability and migration was analyzed. Second, in vivo effect of different dosage patterns and concentrations in the development of hepatic metastasis was analyzed by intra-splenic inoculation of C26 colon carcinoma cells in Balb/c mice. Third, the expression of alpha smooth muscle actin, caspase-3 and Ki-67 expression was quantified by immunohistochemistry, then gene expression levels of inflammatory factors were measured by quantitative RT-PCR. According to our results, OOS reduced tumor cell viability and migration in vitro. Moreover, in vivo daily administration of OOS from the 7th day after tumor cell inoculation decreased the total area and size of metastatic foci in the liver. Furthermore, cell proliferation and fibroblast recruitment was decreased in tumor foci while a higher number of apoptotic cells were observed. Finally, RNA levels for the inflammatory mediators COX-2, IFNγ, IL1β, IL6 and TNFα were reduced in total liver. In conclusion, OOS reduced the metastatic development of colorectal cancer to the liver by increasing apoptosis, and decreasing tumor cell proliferation and fibroblast recruitment in the tumor foci, as well as the expression of inflammatory mediators in total liver. These results point out OOS as a potential supplement to be applied as complementary therapy for the treatment of liver metastasis from colorectal cancer.

Topics: Animals; Apoptosis; Ascorbic Acid; Caspase 3; Cell Proliferation; Colorectal Neoplasms; Folic Acid; Gene Expression Regulation, Neoplastic; Glycyrrhizic Acid; Humans; Ki-67 Antigen; Liver Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Pantothenic Acid; Plant Extracts; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Zinc; Zinc Sulfate

Vitamin C was first suggested to have cancer-fighting properties in the 1930s and has been the subject of controversy ever since. Despite repeated reports of selective cancer cell toxicity induced by high-dose vitamin C treatment in vitro and in mouse models, the mechanism of action has remained elusive.

Topics: Animals; Ascorbic Acid; Colorectal Neoplasms; Female; Humans; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; ras Proteins

The C1561T variant of the glutamate carboxypeptidase II (GCPII) gene is critical for natural methylfolylpolyglutamte (methylfolate) absorption, and has been associated with perturbations in folate metabolism and disease susceptibility. However, little is known on C1561T-GCPII as a risk factor for colorectal cancer. Therefore, this study examined whether C1561T-GCPII influences folate metabolism and adenomatous polyp occurrence.. 164 controls and 38 adenomatous polyp cases were analysed to determine blood folate and plasma homocysteine (Hcy) level, dietary intake of natural methylfolate, synthetic pteroylglutamic acid (PteGlu), vitamin C and C1561T-GCPII genotype.. In controls and cases, 7.3 and 18.4 percent of subjects respectively, were found to have the CT genotype, increasing the risk for adenomatous polyp occurrence 2.86 times (95% CI:1.37-8.0, p=0.035). Total dietary folate, methylfolate and PteGlu intake and the level of erythrocyte folate and plasma Hcy did not predict the occurrence of an adenomatous polyp. However, dietary natural vitamin C intake was associated with adenomatous polyp risk within C1561T-GCPII CT genotype subjects (p=0.037).. The findings suggest that C1561T-GCPII variation may be associated with risk for adenomatous polyp, and vitamin C may modify risk by interacting with the variant gene, its expression product and/or folate substrates.

Topics: Adenomatous Polyps; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; Diet; Folic Acid; Genotype; Glutamate Carboxypeptidase II; Homocysteine; Humans; Middle Aged; Polymorphism, Single Nucleotide; Pteroylpolyglutamic Acids; Risk Factors; Tetrahydrofolates; Vitamins

More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impairs tumor growth in Apc/Kras(G12D) mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations.

Topics: Adenomatous Polyposis Coli Protein; Animals; Ascorbic Acid; Cell Line, Tumor; Colorectal Neoplasms; Dehydroascorbic Acid; Female; Glucose Transporter Type 1; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); Glycolysis; Humans; Mice; Mice, Mutant Strains; Mice, Nude; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); ras Proteins; Reactive Oxygen Species; Xenograft Model Antitumor Assays

Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.. We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.. Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44-0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19-3.66; 3rd tertile 2.48 95%CI: 1.32-4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.. Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.

Topics: Adult; Anthropometry; Antioxidants; Ascorbic Acid; beta Carotene; Chromans; Colorectal Neoplasms; Diet; Feeding Behavior; Female; Follow-Up Studies; Humans; Italy; Life Style; Male; Middle Aged; Nutrition Assessment; Proportional Hazards Models; Prospective Studies; Risk Factors; Vitamin E

Topics: Animals; Ascorbic Acid; Colorectal Neoplasms; Female; Humans; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; ras Proteins

Each month, Chemistry & Biology Select highlights a selection of research reports from the recent literature. These highlights are a snapshot of interesting research done across the field of chemical biology. Our December 2015 selection includes an insight into how vitamin C destroys cancer cells, a new method that makes possible the investigatation of sulfhydration, and the mapping of the CFTR interactome and how it depends on the environmental conditions and differs between wild-type and disease-causing mutant.

Topics: Animals; Ascorbic Acid; Colorectal Neoplasms; Female; Humans; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; ras Proteins

Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; Diet; Dietary Proteins; Dimethylnitrosamine; Female; Humans; Logistic Models; Male; Meat; Middle Aged; Newfoundland and Labrador; Nitroso Compounds; Ontario; Rectal Neoplasms; Risk Factors; Surveys and Questionnaires; Vitamin E

Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day(-1) ) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15-5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer.

Topics: Adult; Aged; Ascorbic Acid; Cell Transformation, Neoplastic; China; Colorectal Neoplasms; Diet; Feeding Behavior; Female; Humans; Meat; Middle Aged; Nitrates; Nitrites; Nitroso Compounds; Prospective Studies; Risk; Surveys and Questionnaires; Women's Health

Topics: Ascorbic Acid; Colorectal Neoplasms; Dietary Fiber; Female; Food Preferences; Fruit; Health Behavior; Health Promotion; Humans; Vegetables

To assess the validity of a 161-item quantitative FFQ (QFFQ) that was developed to evaluate dietary risk factors for a colorectal adenoma case–control study.. A cross-sectional validation study of the QFFQ against 4 d food diary using Pearson correlation coefficients, cross-classification, weighted k statistics and Bland–Altman plotting.. Two hospitals in Sa˜o Paulo, Brazil.. Ninety-seven healthy Japanese-Brazilian adults (40–75 years) were recruited. One participant was excluded from the analysis due to unusual energy intake report.. Mean daily nutrient intakes from the QFFQ were higher than from the food diary. The mean Pearson correlation coefficient for nutrient intakes between the QFFQ and the average of the 4 d food diary was 0?43, and increased to 0?45 after correcting correlations for attenuation due to residual day-to-day variation in the food diary measurements. Adjustment for total energy and further adjustment for age and gender decreased the correlation; however, 77% of observations remained in the same or adjacent quartiles with a mean weighted k of 0?22. Bland–Altman plots on loge-transformed data showed no linear trend between the differences and means for energy, fat, protein, total folate and vitamin C. Compared with the food diary, the QFFQ showed consistently reasonable performance for dietary fibre, total folate, retinol, riboflavin and vitamin C.. This investigation supports the relative validity of the QFFQ as a method for assessing long-term dietary intake. The instrument will be a useful tool in the analysis of diet–adenoma associations in the case–control study.

Topics: Adult; Aged; Ascorbic Acid; Asian People; Brazil; Case-Control Studies; Colorectal Neoplasms; Cross-Sectional Studies; Diet Records; Dietary Fats; Dietary Fiber; Feeding Behavior; Female; Folic Acid; Humans; Linear Models; Male; Middle Aged; Nutrition Assessment; Riboflavin; Risk Factors; Surveys and Questionnaires; Vitamin A

Vitamin C exists in two forms: the reduced (ascorbic acid--AA) and oxidized form (dehydroascorbic acid--DHA). This is a nutrient whose benefits are long known and widely publicized, being most of them related to its antioxidant action. As an antioxidant, the main role of vitamin C is to neutralize free radicals, reducing oxidative stress. However, some controversial studies suggest that this nutrient may have a preventive and therapeutic role in cancer disease due to their possible pro-oxidant activity, promoting the formation of reactive oxygen species that can induce cell death in cancer cells. This factor, coupled with the decrease of antioxidant enzymes and increase of decompartmentalized transition metals in tumor cells may result in the selective cytotoxicity of vitamin C and the subsequent revelation of its therapeutic potential. In this way the first purpose of this work was radioactively label the reduced form of vitamin C with Tc-99m, its quality control by HPLC and the time stability. The second purpose was to use the radioactive complex 99mTc-AA in in vitro and in vivo studies in order to evaluate its uptake by colorectal cancer cells and biodistribution in mices, respectively. The results suggest that the pharmaceutical formulation developed, which was reproducible and stable over time, was residually taken up by colorectal cancer cells. Future studies are needed to deepen our understanding about the radioactive complex 99mTc-AA and clarify the mechanisms of action of vitamin C in oncologic disease.

Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Antineoplastic Agents; Ascorbic Acid; Cell Line, Tumor; Colorectal Neoplasms; Isotope Labeling; Mice; Mice, Inbred BALB C; Mice, Nude; Organotechnetium Compounds; Radiopharmaceuticals; Xenograft Model Antitumor Assays

Vitamin C, available in its reduced form (ascorbic acid; AA) and in its oxidized form (dehydroascorbic acid; DHA), may act in physiological conditions as an antioxidant or pro-oxidant. The aim of this study is to evaluate the cytotoxic effects of pharmacological doses of AA in a human colorectal adenocarcinoma cell line (WiDr) in vitro, through spectrophotometry, clonogenic assays and flow cytometry, and in vivo with xenotransplanted Balb/c nu/nu mice. The results show that the reduced form of vitamin C induces an anti-proliferative and cytotoxic effect in adenocarcinoma colorectal cells under study. The results obtained in vivo after treatment with AA showed a large reduction in the rate of tumor growth. Such understanding can guide decisions about which colorectal cancer patients might potentially benefit from vitamin C pharmacologic therapy.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Dehydroascorbic Acid; Flow Cytometry; Glutathione; Humans; Mice; Mice, Inbred BALB C; Mitochondrial Membranes; Spectrophotometry; Tumor Stem Cell Assay

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; United States; Vitamin B 12; Vitamin B 6; Vitamin E

Topics: Aged; Anticarcinogenic Agents; Ascorbic Acid; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Dietary Supplements; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Randomized Controlled Trials as Topic; United States; Vitamin E

Familial Adenomatous Polyposis (FAP) is a model for the adenoma-carcinoma sequence in several respects. One important area in which FAP serves as a model is chemoprevention. Early prevention trials mainly utilized micronutrients and were largely unsuccessful in preventing or causing regression of adenomas. A new era was ushered in by the recognition that antiarthritic doses of a nonsteroidal anti-inflammatory agent (NSAID), sulindac, could actually induce regression of colorectal adenomas in patients with FAP. Follow-up studies showed positive but variable long-term efficacy for colorectal adenomas, but sulindac appears to lack significant benefit in regressing duodenal adenomas or preventing initial occurrence of adenomas in APC mutation carriers. Due to the well-known side effects of traditional NSAIDs, selective COX-2 inhibitors have been studied rather extensively. Celecoxib has shown benefit in regressing colorectal adenomas and appears to have some duodenal activity as well. Rofecoxib, in smaller trials, showed efficacy as well. However, the entire field of NSAID research in chemoprevention is undergoing reexamination in light of recent demonstration of cardiovascular toxicity in nonfamilial or sporadic adenoma prevention trials. Whether NSAIDs will have a significant future in FAP chemoprevention will depend on a sober assessment of risks and benefits. These same issues will likely foster a more intensive search for new agents. FAP will undoubtedly continue to have a lead role in the testing of new agents, both in the interest of FAP management as such, and in anticipation of trials in nonfamilial adenomas, a problem with even greater societal impact. The historical development of chemoprevention in FAP will be presented, with an emphasis on issues of trial design.

Topics: Adenomatous Polyposis Coli; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Ascorbic Acid; Celecoxib; Chemoprevention; Clinical Trials as Topic; Colorectal Neoplasms; Curcumin; Cyclooxygenase 2 Inhibitors; Drug Therapy, Combination; Eflornithine; Humans; Lactones; Pyrazoles; Sulfonamides; Sulfones; Sulindac; Vitamins

UC (ulcerative colitis) patients have an increased risk of developing colorectal cancer compared with the normal population. The cause underlying this higher risk is not fully defined but includes nutritional and environmental factors concomitant with genetic alterations. We aimed to evaluate genetic stability in the colonic tissue of UC patients in clinical remission compared with the healthy population, and to establish a possible correlation between nutritional habits and these molecular assessments. UC patients (n 42) and healthy controls (n 37) participated in the study. All participants were histopathologically and medically diagnosed. Participants completed five separate 7 d dietary records, food-frequency questionnaires and validated 24 h recalls for nutritional assessment. The extent of chromosome 17 loss and the calculated chromosome index was determined in colon tissue biopsies by fluorescence in situ hybridisation. Correlations between the molecular and nutritional assessments were performed using Pearson's correlation coefficients. Significant differences in the nutritional intake of total fat (65 (SD 15) v. 89 (SD 25) g), cholesterol (330 (SD 168) v. 464 (SD 177) mg), dietary fibre (32 (SD 4.7) v. 9 (SD 4) g), vitamin A (1009 (SD 209) v. 506 (SD 204) microg), vitamin C (308 (SD 108) v. 72 (SD 53) mg) and folic acid (412 (SD 89 microg) v. 187 (SD 107)) were recorded for UC patients compared with controls. Significant correlations were found for the consumption of different food groups and the chromosome index for chromosome 17. The results of our study suggest that the nutritional habits adopted by UC patients during clinical remission may affect key cellular components of the colonic tissue, inducing a high degree of aneuploidy and genetic instability, and probably affecting the development of colon cancer.

Topics: Adult; Aged; Aneuploidy; Ascorbic Acid; Calcium, Dietary; Chromosomes, Human, Pair 17; Colitis, Ulcerative; Colon; Colorectal Neoplasms; Dietary Fats; Dietary Fiber; Energy Intake; Fabaceae; Feeding Behavior; Female; Folic Acid; Genetic Predisposition to Disease; Humans; In Situ Hybridization, Fluorescence; Male; Middle Aged; Nutritional Status; Risk Factors; Vitamin A

The data reported here were obtained from the case-control arm of a large, comprehensive, population-based investigation of colorectal cancer incidence, etiology, and survival, the Melbourne Colorectal Cancer Study, conducted in Melbourne, Australia. This part of the case-control study was designed to identify dietary factors associated with colorectal cancer risk in 715 incident cases compared with 727 age/sex frequency-matched randomly chosen community controls, in which a quantitative assessment of all foods eaten was made. New data are presented on the potential of two groups of micronutrients as protective agents, namely, those involved in DNA methylation, synthesis, and repair (folate, methionine, and vitamins B6 and B12) and those with antioxidant properties (selenium, vitamins E and C, and lycopene). The adjusted odds ratios showed that for folate there was significant protection for rectal cancer in second and third quintiles of consumption but not for colon cancer, and this was similar for methionine consumption. Vitamin B6 consumption was significantly protective for both colon and rectal cancer at the higher quintiles, and this was similar for vitamin B12. Dietary selenium was significantly protective at middle quintiles of consumption at both cancer sites. Dietary vitamins E and C were statistically significantly protective for both colon and rectal cancer at all levels of consumption, and for both vitamins there was a dose-response effect of increasing protection, particularly so for colon cancer. Lycopene was not associated with colorectal cancer risk. A combined model included vitamins E, C, and B12 and selenium as micronutrients protective for colorectal cancer and folate, which, however, showed an increased risk at the highest level of consumption. These data support the proposition that a diet containing the dietary micronutrients involved in DNA methylation (folate, methionine, and vitamins B6 and B12) and some of those with antioxidant properties (selenium and vitamins E and C) may have a role to play in lowering colorectal cancer risk and also that such protection can be achieved by dietary means alone.

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Colorectal Neoplasms; Diet; Diet Surveys; DNA Methylation; Dose-Response Relationship, Drug; Female; Folic Acid; Humans; Lycopene; Male; Methionine; Micronutrients; Odds Ratio; Risk Factors; Selenium; Survival Analysis; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Vitamin E; Vitamins

Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control study of sporadic colorectal adenomas (278 cases; 414 polyp-free controls). Direct-sequencing was used to screen adenomas for mutations in the mutation cluster region of APC; truncating mutations were detected in 161 (58%) of the adenomas. Red meat consumption was significantly differently related to polyps with truncating APC mutation (APC(+) polyps) compared to polyps without truncating APC mutation (APC(-) polyps) (highest vs. lowest tertile, odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.3-1.0). High intake of red meat and fat seemed to increase the risk of APC(-) polyps only (APC(+) vs. controls: red meat, OR = 1.0, 95% CI = 0.6-1.6; fat, OR = 1.1, 95% CI = 0.6-1.9; APC(-) vs. controls: red meat, OR = 1.8, 95% CI = 1.0-3.1; fat, OR = 1.9, 95% CI = 1.0-3.7). Intake of carbohydrates was inversely associated with both polyp groups, most noticeably with APC(-) polyps. Most other evaluated dietary factors were not distinctively associated with a specific APC status. None of the dietary factors was specifically associated with a particular type of truncating APC mutation. Our data suggest that red meat and fat may increase the risk of APC(-) polyps in particular, whereas carbohydrates may especially decrease the risk of APC(-) polyps. However, most examined dietary factors do not appear to be specifically associated with the occurrence of truncating APC mutations in colorectal adenomas but seem to affect both pathways equally.

Topics: Adenoma; Adult; Aged; Alcohol Drinking; Animals; Ascorbic Acid; beta Carotene; Calcium, Dietary; Case-Control Studies; Colorectal Neoplasms; Dairy Products; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; DNA, Neoplasm; Edible Grain; Energy Intake; Feeding Behavior; Female; Fishes; Folic Acid; Fruit; Genes, APC; Humans; Male; Meat; Middle Aged; Mutation; Netherlands; Poultry; Sequence Analysis, DNA; Vegetables

Vitamin E and vitamin C are involved in the defense of the body against free radical and reactive oxygen molecule induced damage. The best characterized biological damage caused by radicals is known as lipid peroxidation. Free radical formation is known to play a major role in the development of cancer. In this study, we measured plasma levels of thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, cholesterol, and vitamins E and C as antioxidants in male patients with colorectal tumors (n = 20, 54.5 +/- 8.3 years). The patients had significantly higher plasma TBARS levels than age-matched healthy subjects (p < 0.001). Plasma vitamin C levels were significantly lower in the patients compared to the healthy subjects (p < 0.001). On the other hand, plasma vitamin E levels in the patients were similar to those of healthy subjects. Plasma cholesterol levels were also found to be significantly elevated in patients with colorectal tumors (p < 0.001). Our results suggest that there is an imbalance between oxidant and antioxidant status in tumor genesis.

Topics: Antioxidants; Ascorbic Acid; Biomarkers, Tumor; Cholesterol; Colorectal Neoplasms; Humans; Lipid Peroxidation; Male; Middle Aged; Thiobarbituric Acid Reactive Substances; Vitamin E

Topics: Adenomatous Polyposis Coli; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Bias; Chemoprevention; Colorectal Neoplasms; Humans; Incidence; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Treatment Outcome; Vitamin E

Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aberrant DNA methylation is associated with low dietary folate intake, which is aggravated by high alcohol intake. The relationship between promoter methylation of genes involved in CRC carcinogenesis and folate and alcohol intake was investigated. Methylation of the APC-1A, p14(ARF), p16(INK4A), hMLH1, O(6)-MGMT, and RASSF1A promoters was studied using methylation-specific PCR in 122 sporadic CRCs, derived from patients with folate and alcohol intake at either the lower or the higher quintiles of the distribution. Overall, promoter hypermethylation frequencies observed were: 39% for APC; 33% for p14(ARF); 31% for p16(INK4A); 29% for hMLH1; 41% for O(6)-MGMT; and 20% for RASSF1A. For each of the tested genes, the prevalence of promoter hypermethylation was higher in CRCs derived from patients with low folate/high alcohol intake (n = 61) when compared with CRCs from patients with high folate/low alcohol intake (n = 61), but the differences were not statistically significant. The number of CRCs with at least one gene methylated was higher (84%) in the low folate intake/high alcohol intake group when compared with the high folate intake/low alcohol intake group (70%; P = 0.085). Despite the size limitations of this study, these data suggest that folate and alcohol intake may be associated with changes in promoter hypermethylation in CRC.

Topics: Aged; Alcohol Drinking; Ascorbic Acid; Cocarcinogenesis; Cohort Studies; Colorectal Neoplasms; Diet; Dietary Fiber; DNA Methylation; DNA, Neoplasm; Dose-Response Relationship, Drug; Energy Intake; Ethanol; Feeding Behavior; Female; Folic Acid; Folic Acid Deficiency; Gene Silencing; Humans; Iron, Dietary; Male; Middle Aged; Netherlands; Pilot Projects; Promoter Regions, Genetic; Risk Factors

Apoptosis, or programmed cell death, may lower the risk of neoplasia by removing genetically damaged or mutated cells. A high rate of apoptosis has been linked to a reduced risk of colorectal adenomas; therefore, it is important to understand factors that impact apoptosis. Antioxidants (e.g., vitamin C) protect cells from harmful oxidation processes but may interfere with apoptosis by protecting genetically damaged cells from reactive oxygen species-dependent cell death. The objective of this study was to evaluate the association between vitamin C intake and apoptosis in normal rectal mucosa. Study participants were part of a large, cross-sectional study, the Diet and Health Study III. Participants were recruited from consecutive, consenting patients who underwent colonoscopy at University of North Carolina Hospitals between August 1, 1998 and March 4, 2000. Vitamin C intake, obtained from a food frequency questionnaire, included both dietary sources and vitamin supplements. Apoptosis was measured by morphological evaluation of H&E-stained sections obtained from pinch biopsy samples of normal rectal mucosa in consenting participants (n = 503). The relationship between vitamin C and apoptosis varied by adenoma status. Among individuals with adenomas, there was an inverse linear association between apoptosis and total vitamin C intake. Similarly, individuals with adenomas in the highest quintile of total vitamin C intake were substantially less likely than those in the lowest quintile to have increased colonic apoptosis (odds ratio, 0.05; 95% confidence interval, 0.01-0.46). Vitamin C was not significantly associated with apoptosis in adenoma-free patients. High vitamin C intake was associated with reduced colorectal apoptosis among individuals with adenomas in this study population. Given that high apoptosis may lower colorectal cancer risk, vitamin C supplements may be contraindicated for patients with a history of adenomas.

Topics: Adenoma; Adult; Antioxidants; Apoptosis; Ascorbic Acid; Colorectal Neoplasms; Cross-Sectional Studies; Eating; Energy Intake; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Multivariate Analysis; North Carolina; Rectum; Statistics as Topic; Treatment Outcome

The purpose of our study was to assess the relationship between simultaneous exposure to alcohol and consumption of micronutrients that may have protective properties against colorectal cancer.. This hospital-based case-control study of colorectal cancer was carried out between January 1998 and November 1999 in Cracow, Poland. A total of 180 cases of colorectal cancer confirmed by histopathology were recruited from the University Hospital in Cracow. An equal number of controls, individually matched by gender and age (+/- 5 years) were chosen from among patients from the same hospital with no history of cancer. An interviewer-administered food frequency questionnaire covering 148 food items, including the quantity consumed, was used to assess the typical dietary pattern.. When the analysis was carried out on quartile intake data, a consistent inverse association was confirmed between the intake of retinol, thiamine or antioxidant micronutrients (carotene, vitamin C and E) and the occurrence of colorectal cancer. Alcohol intake appeared to be an important risk factor for this cancer site, and the risk increased with the amount of pure alcohol intake. The group with deficient intake of retinol, carotene, and vitamins C and E, but with higher consumption of alcohol, incur a noticeably high risk of colorectal cancer (OR=6.79; 95%CI: 2.08-22.18).. The data support the hypothesis that higher consumption of alcohol, when combined with low micronutrient intake, may considerably increase the risk of colorectal cancer.

Topics: Adult; Aged; Alcohol Drinking; Antioxidants; Ascorbic Acid; Carotenoids; Colorectal Neoplasms; Female; Humans; Male; Micronutrients; Middle Aged; Odds Ratio; Risk Factors; Thiamine; Vitamin A; Vitamin E

Patients with advanced cancer exhibit multifaceted defects in their immune capacity, which are likely to contribute to an increased susceptibility to infections and disease progression and to constitute a barrier to immunotherapeutic interventions. A chronic inflammatory condition associated with increased oxidative stress has been suggested as one of the responsible mechanisms behind the tumor-induced immune suppression. We, therefore, speculated that supplementation with the antioxidant vitamin E could enhance the immune functions in patients with advanced cancer.. This hypothesis was here tested in twelve patients with colorectal cancer (Dukes' C and D) who, prior to intervention with chemo- or radiotherapy, received a daily dose of 750 mg of vitamin E during a period of 2 weeks.. Short-term supplementation with high doses of dietary vitamin E leads to increased CD4:CD8 ratios and to enhanced capacity by their T cells to produce the T helper 1 cytokines interleukin 2 and IFN-gamma. In 10 of 12 patients, an increase of 10% or more (average, 22%) in the number of T cells producing interleukin 2 was seen after 2 weeks of vitamin E supplementation, as compared with peripheral blood monocyte samples taken before treatment (P = 0.02). Interestingly, there seemed to be a more pronounced stimulatory effect by vitamin E on naïve (CD45RA(+)) T helper cells as compared with T cells with a memory/activated phenotype.. Dietary vitamin E may be used to improve the immune functions in patients with advanced cancer, as a supplement to more specific immune interventions.

Topics: Adenocarcinoma; Aged; Antigens, CD; Antioxidants; Ascorbic Acid; CD4-CD8 Ratio; Colorectal Neoplasms; Dietary Supplements; Flow Cytometry; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-2; Middle Aged; Neoplasm Staging; Th1 Cells; Time Factors; Vitamin E

The relation between risk of colorectal adenoma and serum concentrations of vitamins A, C, E and carotene was examined in a population-based case-control study of 105 cases of colorectal adenoma and a similar number of hospital controls showing no polyps at colonoscopy and a second control group of population controls. There were no significant associations with serum concentrations of vitamins C and E and carotene. Serum concentrations of vitamin A were significantly inversely related to the risk of colorectal adenoma when cases were compared with both control groups. After adjustment for energy intake, smoking, alcohol, estrogen therapy, body-mass-index and social class the inverse association between vitamin A and colorectal adenoma was even more marked. For the highest versus the lowest quartile of serum levels the adjusted RR was 0.23 (0.07-0.73) in relation to hospital controls and 0.08 (0.02-0.25) in relation to population controls. These findings suggest that the risk of developing colorectal adenomas is reduced in those with high vitamin A levels.

Topics: Adenoma; Adult; Aged; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Risk Factors; Vitamin A; Vitamin E

Some recent epidemiological studies have suggested that use of vitamin C or vitamin E supplements, both of which are important antioxidants, may substantially reduce the risk of colon or colorectal cancer. We examined the association between colorectal cancer mortality and use of individual vitamin C and E supplements in the American Cancer Society's Cancer Prevention Study II cohort. We used proportional hazards modeling to estimate rate ratios among 711,891 men and women in the United States who completed a self-administered questionnaire at study enrollment in 1982, had no history of cancer, and were followed for mortality through 1996. During the 14 years of follow-up, 4404 deaths from colorectal cancer occurred. After adjustment for multiple colorectal cancer risk factors, regular use of vitamin C or E supplements, even long-term use, was not associated with colorectal cancer mortality. The combined-sex rate ratios were 0.89 [95% confidence interval (CI), 0.73-1.09] for 10 or more years of vitamin C use and 1.08 (95% CI, 0.85-1.38) for 10 or more years of vitamin E use. In subgroup analyses, use of vitamin C supplements for 10 or more years was associated with decreased risk of colorectal cancer mortality before age 65 years (rate ratio = 0.48; 95% CI, 0.28-0.81) and decreased risk of rectal cancer mortality at any age (rate ratio = 0.40; 95% CI, 0.20-0.80). Our results do not support a substantial effect of vitamin C or E supplement use on overall colorectal cancer mortality.

Topics: Adult; Age of Onset; Aged; Antioxidants; Ascorbic Acid; Cohort Studies; Colorectal Neoplasms; Dietary Supplements; Female; Humans; Male; Middle Aged; Risk Factors; Sex Factors; United States; Vitamin E

Determination of specific antioxidants for examination of oxidative balance and immune responses may be of value in the early diagnosis of colorectal cancer. In the present report, we investigated urinary excretion of zinc, copper, and neopterin and serum levels of vitamins A, C, and E in 30 patients (age = 64 +/- 12 y) with colorectal cancer at the time of diagnosis and in 30 control subjects (age = 61 +/- 11 y) with benign disorders not associated with a systemic inflammatory response. Urinary excretion of zinc, copper, and neopterin was significantly elevated, and serum concentration of vitamin A was decreased in patients with colorectal cancer; these changes are characteristics of systemic immune activation. These phenomena may be of use for the detection of tumor progression and immune response to neoplasm.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Colorectal Neoplasms; Copper; Female; Humans; Male; Middle Aged; Neopterin; Nutritional Physiological Phenomena; Vitamin A; Vitamin E; Zinc

A long-term sufficient intake of fruits and vegetables reduces significantly the risk of gastric and colorectal carcinoma. It is anticipated that natural antioxidants are involved in this effect in addition to other substances. The aim of this study was to determine levels of vitamins A, C and E, as well as beta-carotene, selenium, zinc and copper in blood of 249 patients with precancerous lesions (atrophic gastritis, gastric hyperplastic polyp, gastric, colonic and rectal adenoma, chronic ulcerative colitis) and in 96 individuals with gastric, colonic or rectal carcinoma and to compare these levels with the values of a control group of 130 healthy individuals. We have found that the frequency of average values of analyzed micronutrients in precancerous groups was decreasing in the order vit C > vit E/vit A > Se > beta-car. The average levels of vitamins and beta-carotene were significantly reduced in all carcinoma groups, while selenium level showed a decrease only in the gastric carcinoma group. Copper level was elevated in the ulcerative colitis group and in all groups with carcinoma. The results indicate a frequent insufficient saturation of organism by natural antioxidants in groups with precancerous lesions and carcinomas of stomach and colorectum. Therefore, it is necessary to increase the general consumption of fruits and vegetables in Slovakia as a part of primary prevention of malignant diseases in these organs. Chemoprevention may be recommended in individuals with precancerous lesions.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Colorectal Neoplasms; Copper; Diet; Female; Humans; Male; Middle Aged; Precancerous Conditions; Selenium; Slovakia; Stomach Neoplasms; Vitamin A; Vitamin E; Zinc

Using data from a case-control study conducted between 1985 and 1992 in northern Italy on 828 cases of colon cancer, 498 cases of rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract disorders, we estimated the percent population attributable risk (PAR) for colorectal cancer in relation to beta-carotene, vitamin C (as markers of a diet rich in fruit and vegetables), red meat and seasoning fat intake, daily meal frequency and family history of the disease. On the basis of multivariate odds ratios, adjusted for total calorie intake, a low intake of beta-carotene accounted for 39% of all the cases and a low intake of vitamin C for 14%. These two micronutrients together explained 43% of all colorectal cancer cases in this population. A high frequency of intake of red meat consumption explained 17% of all cases, and a high score of seasoning fats 4%. A higher daily meal frequency was responsible for 13% of the cases, and these 5 dietary factors together explained 63% of colorectal cancer cases in this population. Family history of colorectal cancer accounted for 4% of all cases. These estimates were similar for colon and rectal cancers separately, in males and females, and in younger and elderly subjects, except for seasoning fats and family history, whose PARs were apparently greater for colon cancer and at younger age. Thus, even though available dietary data were limited in several aspects, and the PAR estimates were based on somewhat arbitrary assumptions regarding the exposure distribution, about two-thirds of all colorectal cancers in this population could be explained in terms of a few risk factors or risk indicators considered. This would correspond to the avoidance of a large proportion of the over 18,000 deaths from colorectal cancer registered per year in the whole of Italy.

Topics: Adult; Age Factors; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Colorectal Neoplasms; Diet; Energy Intake; Feeding Behavior; Female; Humans; Italy; Male; Middle Aged; Multivariate Analysis; Risk Factors; Sex Factors; Surveys and Questionnaires

The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estimate of total energy intake. No apparent trend in risk across intake quintiles was evident for retinol, vitamin D, methionine and calcium. For beta-carotene, ascorbic acid, vitamin E and folate there was a trend of a protective effect with increasing consumption: the RR for the highest versus the lowest quintile was 0.32 for beta-carotene, 0.40 for ascorbic acid, 0.60 for vitamin E and 0.52 for folate. These inverse associations were similar for colon and rectal cancer, and consistent across strata of sex and age. When simultaneous allowance was made for all these micronutrients, besides other covariates, the only persistent protective effects were for beta-carotene (RR = 0.38 for the highest quintile) and ascorbic acid (RR = 0.52). Whether this reflects a specific, or stronger, effect of these micronutrients, rather than problems of collinearity between micronutrients or other limitations of the data, remains open to discussion. Still, this study suggests that specific micronutrients may exert an independent protective effect against colorectal carcinogenesis.

Topics: Adult; Age Factors; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Colorectal Neoplasms; Diet; Female; Folic Acid; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Sex Factors; Vitamin E

The organospecific, 1,2-dimethylhydrazine-induced murine tumor model was used to test the effects on tumor formation of the following dietary supplements: (1) ascorbic acid, 7% per weight; (2) alpha tocopherol, 1% per weight; (3) beta carotene, 1% per weight; and (4) canthazanthin, 1% per weight. Following a four-week dietary acclimation, a 16-week 1,2-dimethylhydrazine induction, and a four-week hiatus, the animals were killed, underwent autopsies, and tumor formation was recorded. The antioxidant supplements of ascorbic acid and alpha tocopherol resulted in a significant decrease in tumor formation when compared with control groups. In contrast, the beta carotene group showed no difference in tumor formation, and canthazanthin, a non-provitamin A carotenoid, resulted in an increase in tumor formation when compared with controls. In addition, the K-gel powder control diet (a carrier medium for alpha tocopherol acetate) had a significantly higher rate of tumor formation than the regular chow and placebo beadlet control diets. In sum, ascorbic acid and alpha tocopherol demonstrated a clear chemopreventive effect, whereas beta carotene had no effect, and canthazanthin appeared to function as a promoter in this organospecific tumor model.

Topics: 1,2-Dimethylhydrazine; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Canthaxanthin; Carotenoids; Colorectal Neoplasms; Dimethylhydrazines; Male; Rats; Vitamin E

In this nested case-control study, 8,006 American Japanese men were examined and interviewed with a dietary questionnaire from 1965 to 1968. After a follow-up period of over 16 years, 102 colon and 60 rectal cancer incident cases were identified. Dietary data from these patients and from 361 cancer-free controls were analyzed for intake of dietary fiber (DF), vitamins, minerals, macronutrients, and selected food groups. We found a significant (p = 0.042) negative association of DF and colon cancer risk among low fat intake men (less than 61 g/d). In this subgroup, the men consuming less than 7.5 g/d of DF had an adjusted relative risk (RR) for colon cancer of 2.28 (95% CI 0.93-5.60), compared to those consuming greater than or equal to 14.8 g/d of DF. We also observed (among the complete group of subjects) a significant (p = 0.011) negative association between vitamin C intake and the risk of colon cancer. Men in the lowest quintile of vitamin C intake (less than 37 mg/d) had an adjusted colon cancer RR of 1.87 (95% CI 1.03-3.37), compared to men in the highest quintile (greater than or equal to 160 mg/d). We view these dietary associations with colon cancer risk with caution. There were no other significant associations of dietary variables with colon cancer risk. Also, there were no significant associations between intake levels of DF, micronutrients, or food groups and rectal cancer risk.

Topics: Ascorbic Acid; Colorectal Neoplasms; Diet; Dietary Fats; Dietary Fiber; Humans; Male; Risk; Vitamin A

With the assumption of the validity of the Hardin Jones principle that the death rate of members of a homogeneous cohort of cancer patients is constant, three criteria for the validity of clinical trials of cancer treatments are formulated. These criteria are satisfied by most published clinical trials, but one trial was found to violate all three, rendering the validity of its reported results uncertain.

Topics: Ascorbic Acid; Clinical Trials as Topic; Cohort Studies; Colonic Neoplasms; Colorectal Neoplasms; Double-Blind Method; Humans; Models, Statistical; Neoplasms