ascorbic-acid and Esophageal-Neoplasms

Although some epidemiological studies have reported the associations between vitamin C and risk of esophageal cancer, these results are inconsistent. Therefore, we performed an updated meta-analysis to explore the associations between dietary vitamin C intake and risk of esophageal cancer. We used PubMed, Embase, and the Web of Science to screen all published articles, which yielded 18 papers eligible for data extraction (involving 4,126 cases and 36,902 controls), and then pooled the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effects model. As we detected the associations in highest category and the lowest type of dietary vitamin C intake, we discovered that dietary vitamin C intake was negatively correlated to the risk of esophageal cancer. The analysis of subgroup showed a significant counter proportion between vitamin C and the risk of ESCC and EAC. Moreover, the dose-analysis indicated that if increasing dietary intake of vitamin C of 50 mg/day, esophageal cancer risk dropped down 10% (OR = 0.81, 95%CI: 0.75-0.87). In summary, our study provides a comprehensive and updated epidemiological evidence to elucidate the relationships between dietary vitamin C and reduction of esophageal cancer risk. Nevertheless, we still need larger case-control and cohort studies to confirm these connections.

Topics: Adenocarcinoma; Ascorbic Acid; Diet; Esophageal Neoplasms; Humans; Nutritional Status; Risk Factors; Vitamins

Barrett's esophagus (BE) is a well-established risk factor for esophageal adenocarcinoma. Our objective was to investigate the effectiveness of lifestyle interventions on BE risk.. We searched PubMed, Embase, and Web of Science up to 30 September 2020. The summary relative risks (RRs) and 95% confidence intervals (CIs) for the highest versus lowest categories of exposure were assessed. Analyses of subgroup, dose-response, sensitivity, and publication bias were conducted.. Sixty-two studies were included that involved more than 250,157 participants and 22,608 cases. Seven lifestyle factors were investigated: smoking, alcohol, body mass index (BMI), physical activity, sleep time, medication, and diet. We observed statistically significant increased BE risks for smoking (RR = 1.35, 95% CI = 1.16-1.57), alcohol intake (RR = 1.23, 95% CI = 1.13-1.34), body fatness (RR = 1.08, 95% CI = 1.03-1.13), less sleep time (RR = 1.76, 95% CI = 1.24-2.49), and proton pump inhibitors use (RR = 1.64, 95% CI = 1.17-2.29). Reduced risks of BE were found for aspirin (RR = 0.70, 95% CI = 0.58-0.84) and the intake of vitamin C (RR = 0.59, 95% CI = 0.44-0.80), folate (RR = 0.47, 95% CI = 0.31-0.71), and fiber (RR = 0.95, 95% CI = 0.93-0.97). The quality of most included studies was high and the subgroup analysis according to the quality score showed significant results (p < 0.05). There was no publication bias for smoking and alcohol. Although the analysis suggested significant evidence of publication bias for BMI, sensitivity analysis showed that the changes in the recalculated RRs were not significant.. The large meta-analysis revealed that lifestyle modifications could reduce the risks of BE and, consequently, esophageal adenocarcinoma.

Topics: Adenocarcinoma; Alcohol Drinking; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Aspirin; Barrett Esophagus; Body Mass Index; Confidence Intervals; Diet; Dietary Fiber; Esophageal Neoplasms; Exercise; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Proton Pump Inhibitors; Publication Bias; Risk; Sleep; Smoking

While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.

Topics: Ascorbic Acid; Diet; Dose-Response Relationship, Drug; Esophageal Neoplasms; Humans; Odds Ratio; Risk Factors; Vitamins

China has some of the highest incidence rates for gastric adenocarcinoma (GA) and esophageal squamous cell carcinoma (ESCC) in the world. Prospective studies suggested that vitamin C may reduce risks; however, associations are unclear because of limited sample size.. The objective was to examine the relation between prediagnostic plasma vitamin C and the risk of GA and ESCC.. A case-cohort study was used to assess the association between prediagnostic plasma vitamin C and incidence of GA (n = 467) and ESCC (n = 618) in the General Population Nutrition Intervention Trial. With the use of multivariate Cox proportional hazards models, we estimated the HRs and 95% CIs. We also conducted a meta-analysis of the literature up to 1 October 2012 on the relation between circulating vitamin C and gastric cancer incidence. Two cohort studies and the current study were included to assess the body of evidence.. For GA, each 20-μmol/L increase in plasma vitamin C was associated with a 14% decrease in risk (HR: 0.86; 95% CI: 0.76, 0.96). Compared with individuals with low plasma vitamin C concentrations (≤28 μmol/L), those with normal concentrations (>28 μmol/L) had a 27% reduced risk of GA (HR: 0.73; 95% CI: 0.56, 0.94). No association between vitamin C concentrations and ESCC was seen. Meta-analysis showed that the risk of incident GA among those with the highest concentration of plasma vitamin C was 31% lower (random-effects-pooled-odds ratio 0.69; 95% CI: 0.54, 0.89) than those in the lowest category.. Our data provide evidence that higher circulating vitamin C was associated with a reduced risk of incident GA, but no association was seen for ESCC.

Topics: Ascorbic Acid; Asian People; Carcinoma, Squamous Cell; China; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Incidence; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Factors; Stomach Neoplasms

Topics: Animals; Ascorbic Acid; Esophageal Neoplasms; Esophagogastric Junction; Gastric Acid; Humans; Nitrates; Nitric Oxide; Nitrous Acid; Stomach Neoplasms

A literature review was made to critically evaluate the ability of ascorbic acid to modulate the incidence of gastrointestinal cancer. A comparison of preclinical, clinical, and epidemiological studies indicated that evidence for ascorbic acid as an inhibitor of carcinogenesis is stronger with regard to gastric cancer and weaker with regard to esophageal and colon/rectal cancer. Insufficient evidence currently exists regarding the oral cavity and the use of ascorbic acid in precancerous conditions such as polyposis and leukoplakia.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Colonic Neoplasms; Esophageal Neoplasms; Gastrointestinal Neoplasms; Humans; Rectal Neoplasms; Stomach Neoplasms

Humans are exposed through ingestion or inhalation to preformed N-nitroso compounds (NOC) in the environment and through the endogenous nitrosation of amino precursors in the body. Activated macrophages and bacterial strains isolated from human infections can enzymatically produce nitrosating agents and NOC from precursors at neutral pH. As a consequence, endogenous nitrosation may occur at various sites of the body, such as the oral cavity, stomach, urinary bladder, and at other sites of infection or inflammation. Numerous substances to which humans are exposed have been identified and shown to inhibit formation of NOC. Such inhibitors include vitamins C and E, certain phenolic compounds, and complex mixtures such as fruit and vegetable juices or other plant extracts. Nitrosation inhibitors normally destroy the nitrosating agents and, thus, act as competitors for the amino compound that serves as substrate for the nitrosating species. Independently, epidemiological studies have already established that fresh fruits and vegetables that are sources of vitamin C, other vitamins, and polyphenols have a protective effect against cancers at various sites and in particular gastric cancer. This article briefly reviews (a) the chemistry of NOC formation and inhibition; (b) the studies in experimental animals that showed that inhibition of endogenous NOC synthesis leads to a reduction of toxic, mutagenic, and carcinogenic effects; (c) recent studies in humans where the degree of inhibition of endogenous NOC synthesis was directly quantified; and (d) the possible contribution of nitrosation inhibitors to human cancer prevention.

Topics: Animals; Antimutagenic Agents; Ascorbic Acid; Cholangiocarcinoma; Esophageal Neoplasms; Humans; Incidence; Infant, Newborn; Macrophage Activation; Macrophages; Neoplasms; Nitroso Compounds; Opisthorchiasis; Phenols; Risk Factors; Stomach Neoplasms; Vitamin E

Studies on the relevance of the N-nitrosamines to esophageal cancer in China are reviewed. Esophageal cancer is a complex and multifactorial problem. Although a causal association between nitrosamines exposure and esophageal cancer in China has not yet been rigorously established, exposure of Lin-Xian subjects to nitrosamines either directly or as a result of their in vivo formation has been detected in our study. Several N-nitrosamines (NDMA, NDEA, NMBzA, NPyr, NPip, and NSAR) in gastric juice collected from Lin-Xian inhabitants have been detected. A correlation was found between the lesions of esophageal epithelium and the amount of nitrosamines present. In addition, the amounts of N-nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, NSAR, and nitrates) excreted in 24-hr urine of subjects in Lin-Xian were significantly higher than those in Fan-Xian, indicating a higher exposure to N-nitroso compound and their precursors of the inhabitants in the high-risk area. The effect of nitrosamines on human esophagus has been investigated at the cellular levels. The amounts of O6-MedG in DNA of esophageal or stomach mucosa of patients from Lin-Xian were higher than that from Europe (Lyon and Essen). The presence of O6-MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O6-MedG in esophageal DNA could be the result of a recent exposure to N-nitroso compounds or a genetically determined reduced cellular capacity for repair of O6-MedG from DNA. The hyperplasia was induced in the esophagus of human fetus that cultured with NMBzA for 2 weeks to 2 months. The intervention studies of esophageal cancer in Lin-Xian have been pursued. Intake of moderate doses of ascorbic acids by Lin-Xian subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in un-dosed subjects in the low-risk area. If N-nitroso compounds are formed in vivo and are among the causative factors of esophageal cancer in Lin-Xian, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds. Thus, the plan of chemoprevention is carried out in Lin-Xian.

Topics: Ascorbic Acid; China; DNA; Epidemiologic Methods; Esophageal Neoplasms; Esophagus; Female; Gastric Juice; Guanine; Humans; Hyperplasia; Nitrosamines; Pregnancy; Time Factors

Topics: Alcohol Drinking; Animals; Ascorbic Acid; Cerebrovascular Disorders; Colonic Neoplasms; Diet; Esophageal Neoplasms; Female; Fishes; Food Preservation; Food Preservatives; Humans; Hypertension; Male; Nitrites; Risk; Smoking; Stomach Neoplasms

Gastrointestinal cancers, mainly oesophageal, gastric, pancreatic and large bowel cancer, account for about 40,000 deaths annually in England and Wales which is 32% of all cancer deaths. Nutritional factors have been implicated in the cause of each cancer and probably act by promoting the effect of carcinogenic substances taken in the diet or produced in the gut. Gastric cancer for example may be due to nitrosamine production in the stomach. This is enhanced by readily available sources of dietary nitrite and nitrate whilst the reaction is inhibited by vitamin C and low temperatures (2 degrees C). By contrast large bowel cancer can be related to high fat and meat intakes whilst a protective role for dietary fibre has been suggested. Dietary factors in the aetiology of oesophageal cancer differ from one high incidence area to another.

Topics: Animals; Ascorbic Acid; Cold Temperature; Diet; Dietary Fats; Dietary Fiber; Digestive System; Esophageal Neoplasms; Gastrointestinal Motility; Gastrointestinal Neoplasms; Humans; Intestinal Neoplasms; Meat; Nitrosamines; Organ Specificity; Pancreatic Neoplasms; Stomach Neoplasms

The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy.. Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation.. In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa.. VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW ( P <0.05). Regarding 0.5% LIS staining, VCS reduced the incidence of acute adverse reactions and heartburn within 1 week ( P <0.05). Both VCS and STS had similar effects. In addition, compared with spraying NS, VCS caused rapid decolorization of iodine-stained esophageal mucosa. After 120 seconds of deiodination, the color of the esophageal mucosa faded by 90%, which is similar to the results seen in the STS group. This contrasts with the results seen in the DW group, which showed fading by only 50.97% ( P <0.05).. VCS can effectively reduce adverse reactions caused by different concentrations of LIS, indicating its important clinical application in the screening of superficial esophageal squamous cell carcinoma.

Topics: Ascorbic Acid; Coloring Agents; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Humans; Iodides; Iodine

Lugol chromoendoscopy facilitates endoscopic visualization of esophageal dysplasia and carcinoma. Vitamin C solution (VCS) can theoretically neutralize free iodine, which causes mucosal irritation. The aim was to assess the safety and efficacy of VCS for relieving adverse symptoms caused by Lugol iodine staining.. Two hundred forty eligible patients were randomized to receive 20 mL of normal saline solution (NS), 5% sodium thiosulfate solution (STS), or 2% VCS after spraying 10 mL of 2% Lugol iodine solution on the mid-distal esophagus. The primary endpoints were statistically significant reductions in acute and late adverse symptom severity scores. The secondary endpoint was the discoloration effect on esophageal brown iodine-stained mucosa.. Spraying both VCS and STS similarly decreased the severity scores of acute (NS vs VCS = 2.58 vs 1.61, P = .040; VCS vs STS = 1.61 vs 1.89, P > .999) and late (NS vs VCS = 1.70 vs 0.91, P = .002; VCS vs STS = 0.91 vs 1.38; P = .212) adverse symptoms after Lugol chromoendoscopy compared with spraying NS. Compared with STS spray, VCS spray alleviated acute acid regurgitation or heartburn (33% vs 15%, P = .017) and late retrosternal discomfort or pain (21% vs 9%, P = .027). Moreover, compared with spraying NS, spraying VCS quickly discolored the iodine-stained mucosa, with a better decolorization score (2.26 vs 3.56, P = .000), and the effects of fading iodine dye were similar between VCS and STS (3.56 vs 3.59, P = .908).. VCS can reduce mucosal irritation symptoms induced by Lugol chromoendoscopy and can be routinely recommended. (Chinese Clinical Trial Registry number: ChiCTR1900022000.).

Topics: Ascorbic Acid; Coloring Agents; Double-Blind Method; Esophageal Neoplasms; Esophagoscopy; Humans; Iodides; Mucous Membrane

This paper aims at evaluating the impact of vitamins intake in the prevention of gastroesophageal reflux disease (GERD), Barrett's oesophagus (BE), and oesophageal adenocarcinoma (EADC). It concentrates primarily on the antioxidant vitamins A, C and E. There were 180 subjects included in the trial, 109 males and 71 females, which were divided in the four groups (70 patients with GERD, 20 patients with BE, 20 patients with EADC, and 70 healthy examinees composing a control group). Their antioxidant vitamins intake was investigated through the usage of the dietary questionnaires. Concentration of the mentioned antioxidant vitamin in serum was detected by HPLC method, and although there were no major statistical differences in their levels between four groups, there existed a correlation between the vitamin serum concentration and the rephlux disease degree. The results showed that the healthy examinees had consumed the greater quantities of the vitamins A, C and E, through both the natural (fruits and vegetables) and the supplementary (industrial vitamin additives) way, than the patients with GERD, BE and EADC. This was reflected in the higher serum levels of the mentioned vitamins in the first group in the comparison with the second group. Based on this, the intake of the vitamins A, C and E through both the natural and the supplementary ways is suggested in order to prevent the development of the GERD, BE and EADC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Barrett Esophagus; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Vitamin A; Vitamin E; Vitamins; Young Adult

The incidence of adenocarcinoma of the esophagus is increasing in most Western industrialized nations especially in white males. The impact of vitamins on the development of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus has not been elucidated. The goal of this pilot-study was to analyze the influence of daily vitamin consumption on the frequency of esophageal carcinoma in Germany.. Ninety-nine patients (males) with esophageal carcinoma (52 with SCC and 47 with AC) were compared to a control group of 50 randomly selected males from the Cologne area. Using a computer program to record the data, patients and controls were questioned in detail about their dietary habits. The interaction between known risk factors and the influence of vitamins on esophageal tumor risk were analyzed using logistic regression analysis.. The univariate analysis showed a significant risk reduction with increased intake of beta-carotene, vitamin C, vitamin E, and folic acid for both AC and for SCC. The results of logistic regression analysis were compatible with the known risk factors for SCC (alcohol and tobacco) and for AC (obesity, tobacco, and alcohol) and showed a significant risk reduction with an intake of vitamin E greater than 13 mg/day (RR=0.13, 95% CI=0.1-0.5, P=0.0004) and vitamin C greater than 100 mg/day (RR=0.33, 95% CI=0.11-0.92, P=0.034) for patients with SCC and similar results for patients with AC.. Our data showed that low intake of vitamin C and E correlates significantly with the development of squamous cell carcinoma as well as adenocarcinoma of the esophagus in males. The relevance of interaction of vitamins with other dietary factors, alcohol, and tobacco are topics of current research.

Topics: Adenocarcinoma; Adult; Alcohol Drinking; Ascorbic Acid; Body Mass Index; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Supplements; Esophageal Neoplasms; Folic Acid; Germany; Humans; Incidence; Male; Pilot Projects; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A; Vitamin E

A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility.

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; China; Cross-Cultural Comparison; Cross-Sectional Studies; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Gastric Mucosa; Humans; Incidence; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world, and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates. To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population, a two-arm randomized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia. During the 6-year intervention, esophageal/gastric cardia cancer mortality was 8% lower among those receiving the active supplements. After 30 and 72 months of intervention, endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus and stomach. In the first survey, in 1987, 833 subjects were endoscoped; in the second survey, in 1991, 396 subjects were examined. The histological diagnoses from each survey were compared by treatment group. Cancer or dysplasia was diagnosed in 28% of the subjects endoscoped in 1987 and 24% of those examined in 1991. The odds ratio for subjects in the treatment group (versus those in the placebo group) having esophageal or gastric dysplasia or cancer was 0.84 (95% confidence interval, 0.61-1.15) in 1987 and 0.86 (0.54-1.38) in 1991. Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys, none of the results was statistically significant, and the findings must be considered inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Cross-Cultural Comparison; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Follow-Up Studies; Gastric Mucosa; Humans; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

In Linxian China, the esophageal/gastric cardia cancer mortality rates are among the highest in the world. There is suspicion that the population's chronic deficiencies of multiple micronutrients are etiologically involved. We conducted two randomized, placebo-controlled nutrition intervention trials to test the effects of vitamin and mineral supplements in lowering the rates of esophageal/gastric cancer. In the first trial, the dysplasia trial, 3318 adults with a cytological diagnosis of esophageal dysplasia received daily supplementation with 26 vitamins and minerals in doses typically 2-3 times the United States Recommended Daily Allowances, or placebos, for 6 years. The second trial, the general population trial, involved 29,584 adults and used a one-half replicate of a 2(4) factorial experimental design which tested the effects of four combinations of nutrients: A, retinol and zinc; B, riboflavin and niacin; C, vitamin C and molybdenum; and D, beta-carotene, vitamin E, and selenium. Doses for these daily supplements ranged from 1 to 2 times the United States Recommended Daily Allowances, and the different vitamin/mineral combinations or placebos were taken for a period of 5.25 years. As part of the general population trial, and end-of-intervention endoscopy survey was carried out in a small (1.3%) sample of subjects to see if supplementation affected the prevalence of dysplasia and early cancer. Herein we review the methods of these trials and the results of the endoscopic survey. Fifteen esophageal and 16 gastric cancers were identified in endoscopic biopsies from the 391 subjects evaluated from two villages, and nearly all were asymptomatic. No significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen with any of the four supplement groups. However, the prevalence of gastric cancer among participants receiving retinol and zinc was 62% lower than those not receiving those supplements (P = 0.09), while participants receiving beta-carotene, vitamin E, and selenium had a 42% reduction in esophageal cancer prevalence (0.34). We have reported separately that cancer mortality over the entire 5.25-year period was significantly reduced among those receiving beta-carotene, vitamin E, and selenium. The findings from the overall trial and the endoscopic sample offer a hopeful sign and should encourage additional studies with these agents in larger numbers of subjects.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Biopsy; Carotenoids; China; Diet; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Niacin; Nutritional Physiological Phenomena; Odds Ratio; Precancerous Conditions; Riboflavin; Selenium; Stomach Neoplasms; Vitamin A; Vitamin E; Zinc

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colloids; Esophageal Neoplasms; Humans; Hydrogen; Nanocomposites; Platinum; Water

Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients' vitamin levels and hematological indicators.. To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance.. EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B. In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B. Vitamin A, D, C and B

Topics: Ascorbic Acid; Esophageal Neoplasms; Female; Humans; Male; Nutritional Status; Vitamin A; Vitamins

Topics: Ascorbic Acid; Double-Blind Method; Esophageal Neoplasms; Esophagoscopy; Humans; Mucous Membrane

We investigated in a cohort study, for the first time using 7-day food diaries (7-DFDs), for age-dependent inverse associations with antioxidants, which have anti-carcinogenic properties, and development of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC).. A total of 24,068 well individuals completed 7-DFDs and donated blood. Vitamins C and E, carotenes, zinc and selenium intakes, and plasma vitamin C were measured. Participants were monitored for 15 years for BO and OAC. Hazard ratios (HRs) were estimated for: quintiles of intake and in participants younger and >=65 years at recruitment, the midpoint of BO peak prevalence.. A total of 197 participants developed BO and 74 OAC. There were no significant associations between antioxidants and BO or OAC in the whole cohort or if >65 years at recruitment. In participants <65 years, for BO, there was an inverse trend across plasma vitamin C quintiles (trend HR = 0.82; 95% CI = 0.71-0.96, P = 0.01), OAC for plasma vitamin C (trend HR = 0.58; 95% CI = 0.37-0.92, P = 0.02) and for dietary vitamins C and E (trend HR = 0.71 95% CI = 0.51-0.99, P = 0.04 and trend HR = 0.70; 95% CI = 0.51-0.96; P = 0.03).. Data supports a role for dietary antioxidants prevent BO and OAC, perhaps at the earlier stages of carcinogenesis.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Barrett Esophagus; Carotenoids; Cohort Studies; Diet; Diet Records; England; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Prospective Studies; Selenium; Vitamin E; Zinc

Tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) and theaflavin-3-3'-digallate (TF3) are two prospective compounds in cancer prevention and treatment. Ascorbic acid (Vc) is essential to a healthy diet as well as being a highly effective antioxidant. In this work, the effects of the combination of EGCG or TF3 with Vc on the apoptosis and caspases-3/9 activities in human lung adenocarcinoma SPC-A-1 cells and esophageal carcinoma Eca-109 cells were determined. Furthermore, the role of mitogen-activated protein kinases (MAPK) pathways in the apoptosis induced by TF3 or EGCG together with Vc were studied using three MAPK inhibitors (ERK inhibitor PD98059, JNK inhibitor SP600125 and p38 inhibitor SB203580). Our results showed that Vc could enhance the EGCG and TF3 induced apoptosis in SPC-A-1 and Eca-109 cells, and this effect involved the activation of caspase-3 and 9. EGCG, TF3 and Vc could activate MAPK pathways respectively, and each compound activated different MAPK subfamilies in different cells. This may explain the enhancement of EGCG and TF3 induced apoptosis by Vc in SPC-A-1 and Eca-109 cells, and will ultimately aid the design of more effective anti-cancer treatments.

Topics: Adenocarcinoma; Anticarcinogenic Agents; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Biflavonoids; Caspase 3; Caspase 9; Catechin; Cell Line, Tumor; Enzyme Inhibitors; Esophageal Neoplasms; Gallic Acid; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; MAP Kinase Signaling System

Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer.. We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study.. A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis.. Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations.. These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

Topics: Aged; Ascorbic Acid; Chlorophyll; Diet; Dimethylnitrosamine; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Iron, Dietary; Linear Models; Male; Middle Aged; Multivariate Analysis; Netherlands; Nitrates; Nitrites; Nitrosation; Prospective Studies; Risk Assessment; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires

While dietary antioxidants are emerging as potentially modifiable risk factors for esophageal adenocarcinoma (EAC), studies on dietary antioxidants and its precursor Barrett's esophagus (BE) are limited. The present study extends previous work on BE by investigating risks of nondysplastic BE, dysplastic BE and EAC associated with intake of antioxidants such as vitamin C, vitamin E, β-carotene, and selenium. Age and sex matched control subjects (n=577 for BE; n=1,507 for EAC) were sampled from an Australian population register. Information on demography, and well established EAC risk factors were obtained using self-administered questionnaires. Intake of antioxidants for patients newly diagnosed with nondysplastic BE (n=266), dysplastic BE (n=101), or EAC (n=299), aged 18-79 years, were obtained using a food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable adjusted logistic regression models. High intake of β-carotene from food and supplement sources combined was inversely associated with risk of dysplastic BE (OR Q4 vs. Q1=0.45; 95%CI: 0.20-1.00). High intake of vitamin E from food sources (OR Q4 vs. Q1=0.43; 95%CI: 0.28-0.67), from food and supplements combined (OR Q4 vs. Q1=0.64; 95%CI: 0.43-0.96), and a high antioxidant index score were inversely associated with risk of EAC. We found no significant trends between intake of β-carotene, vitamin C, vitamin E, and selenium and risk of nondysplastic or dysplastic BE. However, our data suggest that a high intake of β-carotene may be associated with decreased risk of dysplastic BE.

Topics: Adenocarcinoma; Adult; Aged; Antioxidants; Ascorbic Acid; Australia; Barrett Esophagus; beta Carotene; Energy Intake; Esophageal Neoplasms; Feeding Behavior; Female; Fruit; Humans; Male; Middle Aged; Risk Factors; Selenium; Vegetables; Vitamin E

The incidence of esophageal adenocarcinoma in humans is increasing more rapidly than any other malignancy in the United States. Animal studies have demonstrated the efficacy of freeze-dried berry supplementation on carcinogen-induced esophageal squamous cell carcinoma in rats; however, no such studies have been done in esophagoduodenal anastomosis (EDA), an animal model for reflux-induced esophageal adenocarcinoma (EAC) development. Eight-week-old male Sprague-Dawley rats were randomized into 3 groups: EDA + control diet (EDA-CD; n = 10); EDA + 2.5% black raspberry diet (EDA-BRB; n = 11) and EDA + 2.5% blueberry diet (EDA-BB; n = 12). After 2 wk of feeding the respective diets, the rats underwent EDA surgery to induce gastroesophageal reflux and then continued the diet. Measurement of feed intake suggested that all EDA-operated animals had lower feed intake starting at 10 wk after surgery and this was significant close to termination at 24 wk. There were no significant differences in either reflux esophagitis (RE), intestinal metaplasia (IM) (70% in CD, 64% in BRB, and 66% in BB; P = 0.1) or EAC incidence (30% for CD, 34% for BRB, and 25% for BB; P = 0.2) with supplementation. Berry diets did not alter COX-2 levels, but BB diet significantly reduced MnSOD levels (1.23 ± 0.2) compared to control diet (2.05 ± 0.14; P < 0.05). We conclude that a dietary supplementation of freeze-dried BRB and BB at 2.5% (w/w) was not effective in the prevention of reflux-induced esophageal adenocarcinoma in this EDA animal model.

Topics: Adenocarcinoma; Anastomosis, Surgical; Animals; Anthocyanins; Ascorbic Acid; Biomarkers; Blueberry Plants; Cyclooxygenase 2; Dietary Supplements; Disease Models, Animal; Disease Progression; Esophageal Neoplasms; Esophagitis, Peptic; Esophagus; Food Handling; Freeze Drying; Fruit; Linear Models; Male; Plant Preparations; Rats; Rats, Sprague-Dawley; Selenium; Superoxide Dismutase; Weight Gain

The role of antioxidants in the pathogenesis of reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) remains unknown. We evaluated the associations among dietary antioxidant intake and these diseases. We performed an assessment of dietary antioxidant intake in a case control study of RE (n = 219), BE (n = 220), EAC (n = 224), and matched population controls (n = 256) (the Factors Influencing the Barrett's Adenocarcinoma Relationship study) using a modification of a validated FFQ. We found that overall antioxidant index, a measure of the combined intake of vitamin C, vitamin E, total carotenoids, and selenium, was associated with a reduced risk of EAC [odds ratio (OR) = 0.57; 95% CI = 0.33-0.98], but not BE (OR = 0.95; 95% CI = 0.53-1.71) or RE (OR = 1.60; 95% CI = 0.86-2.98), for those in the highest compared with lowest category of intake. Those in the highest category of vitamin C intake had a lower risk of EAC (OR = 0.37; 95% CI = 0.21-0.66; P-trend = 0.001) and RE (OR = 0.46; 95% CI = 0.24-0.90; P-trend = 0.03) compared with those in the lowest category. Vitamin C intake was not associated with BE, and intake of vitamin E, total carotenoids, zinc, copper, or selenium was not associated with EAC, BE, or RE. In conclusion, the overall antioxidant index was associated with a reduced risk of EAC. Higher dietary intake of vitamin C was associated with a reduced risk of EAC and RE. These results suggest that antioxidants may play a role in the pathogenesis of RE and EAC and may be more important in terms of progression rather than initiation of the disease process.

Topics: Adenocarcinoma; Aged; Antioxidants; Ascorbic Acid; Barrett Esophagus; Carotenoids; Case-Control Studies; Copper; Diet; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Minerals; Odds Ratio; Risk Factors; Selenium; Vitamin E; Zinc

Combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) has already been shown to promote rat forestomach carcinogenesis, possibly due to nitric oxide generation under acidic conditions. We hypothesized that a similar effect might occur in the esophagus when the luminal pH is decreased by acid reflux. To clarify this possibility, reflux esophagitis model rats (F344 male) were coadministered 0.2% NaNO2 in the drinking water and 1% AsA in the diet. After 32 weeks of the combined treatment, a significant increase in the incidence of epithelial hyperplasias of the lower-middle and lowest parts of the esophagus were observed compared with the basal-diet group, along with exacerbation of dysplasia and extension of the lesions. Additionally, one squamous cell papilloma was found only in the combined-treatment group. Subsequently, we confirmed the enhancing effects of NaNO2 and AsA cotreatment in the rat N-bis(2-hydroxypropyl)nitrosamine-initiated esophageal tumorigenesis model. The incidence of hyperplasia was enhanced in all segments, along with the incidence and multiplicity of squamous cell papillomas in the lowest segment of the esophagus. Thus, the data demonstrate that combined treatment with NaNO2 and AsA exerts promoting effects on rat esophageal carcinogenesis under acid reflux conditions, as in the forestomach. These findings suggest that the risk of excessive intake of a combination of nitrite and antioxidants for esophageal carcinogenesis is appreciable, particularly in patients with reflux esophagitis.

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Cocarcinogenesis; Disease Models, Animal; Esophageal Neoplasms; Esophagitis, Peptic; Food Preservatives; Male; Rats; Rats, Inbred F344; Sodium Nitrite

The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339 men and women with histologically confirmed Barrett's esophagus. Participants underwent baseline and periodic follow-up exams, which included endoscopy and self-administered questionnaires on diet, supplement use, and lifestyle characteristics. Use of multivitamins and 4 individual supplements was calculated using time-weighted averages of reported use over the observational period. Cox proportional-hazards models were used to calculate hazard ratios (HR) for each endpoint: EA, tetraploidy, and aneuploidy. During a mean follow-up of 5 yr, there were 37 cases of EA, 42 cases of tetraploidy, and 34 cases of aneuploidy. After controlling for multiple covariates including diet, nonsteroidal anti-inflammatory drug use, obesity, and smoking, participants who took 1 or more multivitamin pills/day had a significantly decreased risk of tetraploidy [HR = 0.19; 95% confidence interval (CI) = 0.08-0.47) and EA (HR = 0.38; 95% CI = 0.15-0.99] compared to those not taking multivitamins. Significant inverse associations were also observed between risk of EA and supplemental vitamin C (> or = 250 mg vs. none: HR = 0.25; 95% CI = 0.11-0.58) and vitamin E (> or = 180 mg vs. none: HR = 0.25; 95% CI = 0.10-0.60). In this cohort study, use of multivitamins and single antioxidant supplements was associated with a significantly reduced risk of EA and markers of neoplastic progression among individuals with Barrett's esophagus.

Topics: Adenocarcinoma; Adult; Aged; Aneuploidy; Ascorbic Acid; Barrett Esophagus; Cell Transformation, Neoplastic; Chemoprevention; Cohort Studies; Dietary Supplements; Disease Progression; Drug Therapy, Combination; Endoscopy; Esophageal Neoplasms; Female; Flow Cytometry; Follow-Up Studies; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Vitamin E; Vitamins

Bile acids are often refluxed into the lower oesophagus and are candidate carcinogens in the development of oesophageal adenocarcinoma. We show here that the secondary bile acid, deoxycholic acid (DCA), is the only one of the commonly refluxed bile acids tested here, to show genotoxicity, in terms of chromosome damage and mutation induction in the human p53 gene. This genotoxicity was apparent at both neutral and acidic pH, whilst there was a considerable increase in bile-induced toxicity at acidic pH. The higher levels of cell death and low cell survival rates at acidic pH may imply that acid bile exposure is toxic rather than carcinogenic, as dead cells do not seed cancer development. We also show that DCA (at neutral and acid pH) induced the release of reactive oxygen species (ROS) within the cytoplasm of exposed cells. We further demonstrate that the genotoxicity of DCA is ROS mediated, as micronucleus induction was significantly reduced when cells were treated with DCA + the anti-oxidant vitamin C. In conclusion, we show that DCA, is an effective genotoxin at both neutral and acidic pH. As bile acids like DCA can induce DNA damage at neutral pH, suppressing the acidity of the refluxate will not completely remove its carcinogenic potential. The genotoxicity of DCA is however, ROS dependent, hence anti-oxidant supplementation, in addition to acid suppression may block DCA driven carcinogenesis in Barrett's patients.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Barrett Esophagus; Carcinoma, Squamous Cell; Cell Survival; Deoxycholic Acid; Detergents; DNA Damage; Esophageal Neoplasms; Humans; Hydrogen-Ion Concentration; Micronucleus Tests; Reactive Oxygen Species; Tumor Cells, Cultured; Tumor Suppressor Protein p53

The luminal microenvironment including acid and nitric oxide (NO) has been implicated in Barrett's esophagus carcinogenesis. We investigated the ability of acid and NO to induce DNA damage in esophageal cells.. Transformed and primary Barrett's esophagus and adenocarcinoma cells were exposed to either acid, (pH 3.5), +/- antioxidant or NO from a donor or generated by acidification of nitrite in the presence of ascorbate +/- NO scavenger. Phosphorylation of histone H2AX and the neutral comet assay were used to detect DNA double-strand breaks (DSBs). Intracellular levels of reactive oxygen species and NO were detected with fluorescent dyes. Mitochondrial viability was measured with a rhodamine dye. Long-term survival was assessed by clonogenic assay.. Exposure to acid (pH 3.5) for > or =15 minutes induced DSBs in all cell lines (P < .05). There was a concomitant increase in intracellular reactive oxygen species in the absence of mitochondrial damage, and pretreatment with antioxidants inhibited DNA damage. Exposure to physiologic concentrations of NO produced from the NO donor or acidification of salivary nitrite induced DSBs in a dose- (>25 micromol/L) and cell-dependent manner (adenocarcinoma >Barrett's esophagus, P < .05). This occurred preferentially in S-phase cells consistent with stalled replication forks and was blocked with a NO scavenger. NO also induced DSBs in primary Barrett's esophagus cells treated ex vivo. Cells were able to survive when exposed to acid and NO.. Both acid and NO have the potential to generate DSBs in the esophagus and via distinct mechanisms.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Barrett Esophagus; Cell Line, Tumor; Cell Survival; Cell Transformation, Neoplastic; Comet Assay; DNA Breaks, Single-Stranded; Dose-Response Relationship, Drug; Esophageal Neoplasms; Gastric Acid; Histones; Humans; Hydrazines; Hydrogen-Ion Concentration; Mitochondria; Nitric Oxide; Nitric Oxide Donors; Phosphorylation; Reactive Oxygen Species; S Phase; Sodium Nitrite; Time Factors

To study the changes of vitamin nutritional status of residents in a high-risk area of esophageal cancer.. 8 towns where nutrition survey had been done were selected, 2 villages were randomly selected from each town and 30 families were randomly selected per village. The blood and 4h burden urine samples were collected from subjects. The serum vitamin A, blood total ascorbic acid and glutathione reductase activition coefficient (AC) in red blood cell were determinde by using of trifluoroacetic acid colorimetry, 2, 4-dinitrophenylhydrazine colorimetric method and Sauberlich method respectively. The contents of vitamin B2 , reduction ascorbic acid and total ascorbic acid in 4h burden urine were measured by using of fluorescent pectrophotometry,2,6-Dichloro-N-(4-hydroxyphenyl)-1,4-benzoquinoneimine titrimetric method and 2,4-dinitrophenylhydrazine colorimetric method respectively. The results were analyzed and compared with those of in 1980, 1983 and 1984. The t-test or chi2-test was carried out.. The level of serum retinal in residents living in Ren cun, Dongyao and Hejian is significantly higher than that of in 1982 (P < 0.01). The level of vitamin B2 in 4h burden urine in residents living in Yaocun, Rencun and Heshun are significantly higher than that of in 1982 or 1984 (P < 0.01). The number of ribflavin deficiency of population living in Dongyao, Hejian, Yaocun and Rencun are significantly lower than that of in 1982 or 1983 (P < 0.01) according to the content of 4h burden urine and glutathione reductase activation coefficient (AC) in red blood cell; the number of vitamin C deficiency of population living in Dongyao, Hejian,Yao cun, Ren cun and Heshun are significantly lower than that of in 1982 or 1983 (P < 0.01) according to blood total ascorbic acid and the ascorbic acid content of 4h-burden urine and.. Vitamin nutritional status of residents in a high-risk area of esophageal cancer have been improved.

Topics: Ascorbic Acid; China; Esophageal Neoplasms; Glutathione Reductase; Humans; Nutritional Status; Riboflavin; Sampling Studies; Vitamin A

When saliva, with its high nitrite content derived from the enterosalivary recirculation of dietary nitrate, meets acidic gastric juice, the nitrite is converted to nitrous acid, nitrosative species, and nitric oxide. In healthy volunteers this potentially mutagenic chemistry is focused at the gastric cardia. We have studied the location of this luminal chemistry in Barrett's patients during acid reflux.. Ten Barrett's patients were studied before and after administration of 2 mmol nitrate. Using microdialysis probes we measured nitrite, ascorbic acid, total vitamin C, and thiocyanate concentrations and pH simultaneously in the proximal oesophagus, Barrett's segment, hiatal sac, proximal stomach, and distal stomach. In a subgroup, real time nitric oxide concentrations were also measured.. During acid reflux, Barrett's segment was the anatomical site with maximal potential for acid catalysed nitrosation, with its median concentration of nitrite exceeding that of ascorbic acid in two of 10 subjects before nitrate and in four of nine after nitrate. Thiocyanate, which catalyses acid nitrosation, was abundant at all anatomical sites. On entering the acidic Barrett's segment, there was a substantial fall in nitrite and the lowest ascorbic acid to total vitamin C ratio, indicative of reduction of salivary nitrite to nitric oxide at this anatomical site. Episodes of acid reflux were observed to generate nitric oxide concentrations of up to 60 muM within the Barrett's segment.. The interaction between acidic gastric refluxate and nitrite rich saliva activates potentially mutagenic luminal nitrosative chemistry within Barrett's oesophagus.

Topics: Aged; Ascorbic Acid; Barrett Esophagus; Esophageal Neoplasms; Esophagoscopy; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Microdialysis; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Nitrosation; Precancerous Conditions; Saliva; Thiocyanates

Chemotherapy is increasingly utilised in multimodal protocols to try and improve outcomes. Cisplatin and 5-fluorouracil (5-Fu) are the mainstay of chemotherapeutic regimens, and an understanding of sensitivity and resistance of esophageal cancer to these agents is of considerable clinical importance. Antioxidants may modulate the response to chemotherapy, and in this study we examined the effect of vitamin C on 5-Fu and cisplatin cytotoxicity and related pathways in the esophageal cancer cell lines OE33 and SKGT-4. The antiproliferative effect of antitumor agents was measured by the MTT assay, and the transcription factors NF-kappaB and AP-1 pathways were assessed by electrophoretic mobility gel shift assay. 5-Fu and cisplatin demonstrated marked morphological changes and decreased cell proliferation. A combination of vitamin C with 5-Fu or cisplatin exerted a significantly enhanced cytotoxic effect compared to both drugs individually. Treatment of esophageal cancer cells with 5-Fu and cisplatin induced NF-kappaB and AP-1 activation. Pretreatment with vitamin C inhibited 5-Fu or cisplatin induced NF-kappaB nuclear translocation and DNA binding activity, but vitamin C had no effect on IkappaB-alpha protein levels. Vitamin C also inhibited 5-Fu- and cisplatin-induced AP-1 activation. Our data demonstrate that vitamin C enhances the antitumor activity of 5-Fu and cisplatin, in part by inhibiting translocation of NF-kappaB and AP-1, and sensitizes cancer cells to drug-induced cell death. The data suggest that vitamin C supplementation may improve the efficacy of chemotherapy for esophageal cancer.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cell Proliferation; Cisplatin; Drug Interactions; Esophageal Neoplasms; Fluorouracil; Humans; NF-kappa B; Transcription Factor AP-1; Tumor Cells, Cultured

High luminal concentrations of nitric oxide are generated at the human gastro-oesophaegal junction and within Barrett's oesophagus due to the reduction of salivary nitrite to nitric oxide by acidic gastric juice. Salivary nitrite is derived from the entero-salivary recirculation of dietary nitrate. Our aim was to determine whether nitric oxide generated within the lumen will exert nitrosative stress on the adjacent epithelium. A benchtop model was constructed reproducing the nitrite chemistry occurring within the lumen of the upper gastrointestinal tract where saliva encounters acidic gastric juice. It incorporated an epithelial compartment maintained at pH 7.4 and separated from the lumen by a hydrophobic barrier with the properties of the epithelial lipid cell membrane. The secondary amine morpholine was used to measure N-nitroso compound formation in both the lumen and epithelial compartment. Adding 100 micro M nitrite to the acidic (pH 1.5) luminal compartment depleted of ascorbic acid generated 6.2 +/- 2.0 micro M (mean +/- SE) N-nitrosomorpholine in that compartment and 2.2 +/- 0.1 micro M nitrosomorpholine in the epithelial compartment at 30 min. When 100 micro M nitrite was added to the acidic luminal compartment containing physiological concentrations of ascorbic acid, all the nitrite was immediately converted to nitric oxide and no N-nitrosomorpholine was formed within that compartment. However, the nitric oxide rapidly diffused from the luminal compartment into the epithelial compartment and there generated very high concentrations of N-nitrosomorpholine (137 +/- 5.6 micro M at 30 min). The addition of ascorbic acid or glutathione to the epithelial compartment could only reduce nitric oxide-induced nitrosation within that compartment by 40%. The nitrate-derived nitric oxide generated within the lumen where saliva encounters gastric acid is likely to exert substantial nitrosative stress on the adjacent epithelium. This may contribute to the high prevalence of mutagenesis at this anatomical site.

Topics: Ascorbic Acid; Cell Membrane; Diet; Dose-Response Relationship, Drug; Epithelium; Esophageal Neoplasms; Glutathione; Humans; Hydrogen-Ion Concentration; Models, Biological; Morphine; Mutagenesis; Nitrates; Nitric Oxide; Nitrites; Nitrogen; Saliva; Stomach Neoplasms; Stress, Physiological; Time Factors

Linxian, China, is a region with high incidence of esophageal cancer and a history of poor nutritional status. Nutrition Intervention Trials were conducted in this area from 1985 through 1991 and found a reduction in total cancer mortality in the group receiving supplementation of beta-carotene/selenium/alpha-tocopherol. The positive results of those trials have, in part, been ascribed to the poor nutritional status of this population. To investigate more recent food patterns, nutrient intakes, and seasonal variations in the diet, dietary surveys were conducted among the residents of Linxian in 1996. Food consumption data were collected among 104 households in spring and 106 households in autumn using a method of food inventory changes. Intake of nutrients was estimated and compared to the Chinese Recommended Dietary Allowance (RDA). In both seasons, the five most common food groups consumed were cereals, fresh vegetables, yams, seasoning, and eggs. Low nutrient intakes were found for selenium (79% RDA and 66% RDA), zinc (72% RDA and 62% RDA), vitamin B2 (64% RDA and 52% RDA), and calcium (53% RDA and 39% RDA) in both spring and autumn. A large seasonal variation was seen in the consumption of leafy vegetables, root vegetables and eggs, all of which might have contributed to the lower intake of vitamin A (25% RDA), vitamin C (75% RDA), protein (76% RDA), and vitamin E (78% RDA) in autumn. These indicate that the nutrient intake in Linxian is inadequate for a number of vitamins and minerals including those shown to be associated with esophageal cancer.

Topics: Adolescent; Adult; Aged; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Calcium, Dietary; Child; China; Diet; Diet Surveys; Dietary Supplements; Edible Grain; Eggs; Esophageal Neoplasms; Female; Food; Humans; Male; Middle Aged; Nutrition Policy; Nutritional Physiological Phenomena; Riboflavin; Seasons; Selenium; Vegetables; Vitamin A; Zinc

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.

Topics: Adenocarcinoma; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Cardia; Case-Control Studies; Diet; Dietary Supplements; Drug Synergism; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Multivariate Analysis; Oxidative Stress; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vitamin E

The purpose of this study was to investigate the possible contribution of different dietary nutrients in the development of esophageal cancer (EC) in the Caspian littoral of Iran. Forty-one cases and 145 members of their households were matched for age and gender with 40 non-blood-relative controls and 130 members of their households for their nutrient intake. A standard 24-hour dietary recall questionnaire was used to estimate the daily intake of energy, protein, P, Fe, Na, K, vitamins C and A, thiamin, riboflavin, and niacin. Dietary nutrient deficiency was defined as less than 75% of the World Health Organization human nutritional requirements, except for P, Na, and K, for which the United States Recommended Dietary Allowances were followed. The results indicate the following: (1) The mean daily intake of all nutrients, except for riboflavin, was significantly lower in cases than in control subjects (P < .05); (2) with the exception of protein, riboflavin, and phosphorus, significant correlation was observed between the pattern of nutrient intake and health status of the study subjects (P < .05); and (3) dietary deficiency of niacin and phosphorus was associated significantly with the risk of EC development among case and control households (P < .01-.001), indicating that persons living in case households with dietary deficiencies of these nutrients have more than twice the risk of developing EC tumors than those living in control households. In conclusion, apparently some nutrients, such as P and niacin, may play a role in the etiology of esophageal cancer, and the status of these nutrients may be used eventually as an epidemiologic predictive marker for EC in the Caspian littoral of Iran and perhaps other regions.

Topics: Ascorbic Acid; Case-Control Studies; Dietary Fats; Esophageal Neoplasms; Female; Humans; Iran; Iron; Male; Niacin; Nutritional Physiological Phenomena; Odds Ratio; Phosphorus; Potassium; Riboflavin; Risk Factors; Sex Factors; Sodium; Surveys and Questionnaires; Thiamine; Vitamin A

An increasing number of reports suggest that diet has an impact on oesophageal cancer risk in Western countries, where alcohol and tobacco are held to be the major determinants of the risk. The aim of our study was to identify dietary factors influencing the risk of oesophageal cancer in France and to determine whether certain of these could explain some of the geographical variations. We conducted a multicentre case-control study in 3 regions expected to have different diet and drinking habits (Normandy, Burgundy and Midi Pyrénées). Two hundred eight cases and 399 controls, all males, were interviewed about their eating, drinking and smoking habits. After proper adjustment for drinking and smoking, high consumption of butter and low consumption of fresh fish, vegetables and fruits were associated strongly and independently with an increase in oesophageal-cancer risk. Consistently, cholesterol appeared as a risk factor and vitamin E, vitamin D and phosphorus as independent protective factors. The protective effect of citrus and other fresh fruits (vitamin C) was confined strictly to heavy drinkers. Our findings suggest that more than one-third of the high incidence of oesophageal cancer in northwest France could be explained by the local excess in butter consumption, whereas geographical variations in consumption of dietary protective factors could explain no more than 10% of it. Overall, a large proportion (57%) of the excess incidence of oesophageal cancer in northwest France could be explained by local dietary habits, e.g., drinking hot Calvados liquor and excessive consumption of butter.

Topics: Alcohol Drinking; Animals; Ascorbic Acid; Butter; Carcinoma, Squamous Cell; Case-Control Studies; Diet; Dietary Fats; Esophageal Neoplasms; France; Fruit; Humans; Male; Multicenter Studies as Topic; Seafood; Smoking; Vegetables; Vitamin D; Vitamin E

A series of 16 experiments, using a total of 2,000 BD6 rats, was designed in order to assess the ability of 8 individual agents or their combinations to modulate the liver and oesophageal carcinogenesis induced by multiple doses of diethylnitrosamine (DEN). Of the antioxidants tested, sodium selenite, ascorbic acid, and butylated hydroxytoluene generally exhibited protective effects on both types of tumors. In contrast, retinoic acid behaved as a promoter of DEN hepatocarcinogenesis, but this effect could be eliminated by its combination with either selenite or butylated hydroxytoluene. Caffeine and theophylline, when individually assayed, were devoid of significant protective effects, and the latter methylxanthine stimulated oesophageal tumorigenesis when administered after exposure to the carcinogen. Caffeine tended to decrease the multiplicity of liver tumors and potentiated the inhibitory effect of selenite in the liver. Irrespective of combination with caffeine, treatment with phenobarbital before each DEN injection tended to reduce the multiplicity of both liver and oesophageal tumors. On the other hand, the metabolic inhibitor diethyldithiocarbamate, given after each DEN injection, dramatically enhanced the incidence and multiplicity of oesophageal tumors. Thus, on the whole, modulation of DEN carcinogenesis varied depending on test agents, their combinations, dosages, treatment schedules, and target organ.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Caffeine; Diethylnitrosamine; Disease Models, Animal; Esophageal Neoplasms; Female; Liver Neoplasms, Experimental; Neoplasms, Experimental; Phenobarbital; Rats; Rats, Inbred Strains; Survival; Theophylline; Tretinoin

Topics: Adult; Ascorbic Acid; China; Esophageal Neoplasms; Humans; Middle Aged; Randomized Controlled Trials as Topic; Stomach Neoplasms

Overnight urine samples were collected from approximately 60 male adults in each of 69 counties of China in 1989. Two specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids and nitrate were measured in urine samples and correlated with cumulative mortality rates for subjects aged between 0 and 64 years in the 1970s. Oesophageal cancer mortality rates were positively and significantly associated with (i) urinary levels of excreted N-nitrosoproline (NPRO) (after proline and ascorbic acid loading or proline loading only), (ii) N-nitrososarcosine levels, and (iii) nitrosation potential (the decrease in the amount of urinary NPRO after adding ascorbic acid to the proline load). There were also positive correlations between the urinary level of NPRO or other N-nitrosamino acids and that of nitrate. The urinary excretion of nitrate was associated with consumption of various nitrate-rich vegetables. The results suggest that N-nitroso compounds (NOC) or other nitrite-derived carcinogens are implicated in the aetiology of oesophageal cancer in China.

Topics: Adult; Ascorbic Acid; China; Esophageal Neoplasms; Humans; Male; Middle Aged; Nitrates; Nitrosamines; Proline; Smoking; Vegetables

A total of 391 gastric juice samples was collected from Ji Yuan and An Shi counties, high and medium risk areas of esophageal carcinoma in Henan province. NDMA, NDEA, NMBzA, NPip and unknown compounds were assayed in the fasting gastric juice. Among these nitrosamines, NMBzA, NPyr and NPip were specific in inducing esophageal cancer in animals. The amount of nitrosamines in the gastric juice collected from Ji Yuan county was higher than that from An Shi county. The exposure level of nitrosamines of subjects from these two localities were significantly different (P < 0.001). There was a positive relationship between the nitrosamines exposure level and esophageal cancer mortality rate. The amount of gastric N-nitrosamines from An Shi subjects as treated with vitamin C was reduced. It is evident that vitamin C can inhibit N-nitrosamine formation in the stomach, thereby, reducing the N-nitrosamines exposure level.

Topics: Adult; Aged; Ascorbic Acid; Dimethylnitrosamine; Esophageal Neoplasms; Esophagus; Female; Gastric Juice; Humans; Hyperplasia; Male; Middle Aged; N-Nitrosopyrrolidine; Nitrosamines; Precancerous Conditions

In animal experiments with Wistar rats we attempted to determine if oral application of Vitamin C inhibits or delays carcinogenesis due to oral administered N-Nitrosopiperidine (NTP). One group of animals received NTP only, two other groups NTP and Vitamin C either alternating or simultaneously. A fourth group receiving only Vitamin C served as control. Carcinomas of the esophagus, stomach and liver developed in response to NTP application. The additional administration of Vitamin C neither inhibited nor delayed the development of carcinomas.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Carcinogens; Dose-Response Relationship, Drug; Esophageal Neoplasms; Female; Liver Neoplasms; Male; Neoplasms, Experimental; Nitrosamines; Rats; Rats, Inbred Strains; Stomach Neoplasms

Using dietary, blood nutrient, and esophageal cancer mortality data from 65 Chinese counties, we examined several correlations to help provide clues to the influence of diet and nutrition on the geographic variation of esophageal cancer in China. Esophageal cancer mortality was significantly inversely related to reported fruit consumption and to plasma ascorbic acid concentration. The age-adjusted mortality rates were more than three times higher for counties in the lowest compared with the highest quartile of fruit intake or plasma vitamin C. Positive correlations with intake of moldy vegetables were observed but not with tobacco and alcohol consumption. There were suggestive inverse associations with blood selenium and riboflavin but little effect of fat-soluble vitamins. Limitations of ecological data preclude causal inferences, but the relationships provide leads to dietary factors that may contribute to the exceptionally high rates of esophageal cancer in several areas of China.

Topics: Adolescent; Adult; Ascorbic Acid; Child; Child, Preschool; China; Diet; Esophageal Neoplasms; Female; Fruit; Humans; Infant; Male; Middle Aged; Nutritional Status; Riboflavin; Selenium; Sex Factors; Survival Rate

The study was concerned with the influence of tocopherol and ascorbic acid on induction of tumors by N-nitrososarcosine ethyl ester (NSEE) in rats. In the first series of experiments, NSEE was given orally in the daily dose of 100 mg/kg body weight during 8 weeks while alpha-tocopherol acetate was administered in the dose of 600 mg/kg food during the following 32 weeks. In the second series, NSEE was given intragastrically in the dose of 50 mg/kg body weight daily during 16 weeks whereas for the following 16 weeks, the animals received 20 g/kg food ascorbic acid. The rats were sacrificed at 40 (series 1) and 32 weeks (series 2) of the experiment. NSEE induced tumors of the esophagus and forestomach in more than 90% of cases, mainly papillomas and--less frequently--carcinomas, five tumors per rat, on the average. Treatment with tocopherol was followed by a 37% decrease in the incidence of esophageal and forestomach tumors, an approximately two-fold drop in their multiplicity as well as by lowered incidence of carcinomas. Ascorbic acid did not affect tumor induction.

Topics: alpha-Tocopherol; Animals; Antineoplastic Agents; Ascorbic Acid; Carcinogens; Drug Screening Assays, Antitumor; Esophageal Neoplasms; Esophagus; Male; Nitrosamines; Rats; Stomach; Time Factors; Tocopherols; Vitamin E

Urine and blood levels of ascorbic acid (AA) were measured in healthy subjects (40), cases of cancer of the lung (74), stomach (32) and esophagus (12). AA levels were decreased in cancer patients, particularly, in those with gastric and esophageal tumors. A correlation between the decrease of AA level and the increase in blood concentrations of malonic and pyruvic acids was established. Administration of 1.5 g AA for 7 days was followed by blood-AA level returning practically to normal matched by decrease in lactate and pyruvate concentrations. Also, a correlation between postoperative complication frequency and AA deficit was shown. Correction of AA level was found to be an effective means of postoperative complication prevention.

Topics: Administration, Oral; Ascorbic Acid; Ascorbic Acid Deficiency; Combined Modality Therapy; Esophageal Neoplasms; Humans; Infusions, Intravenous; Lactates; Lactic Acid; Lung Neoplasms; Oxidation-Reduction; Preoperative Care; Pyruvates; Pyruvic Acid; Stomach Neoplasms

Topics: Adult; Alcoholism; Ascorbic Acid; Esophageal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Intestinal Neoplasms; Male; Middle Aged; Nutritional Physiological Phenomena; Risk Factors; Stomach Neoplasms

Topics: Animals; Ascorbic Acid; Carcinogens; Dinoprostone; Esophageal Neoplasms; Ethanol; Male; Nitrosamines; Prostaglandins E; Rats; Rats, Inbred Strains; Tegafur

Carcinogenic and promoting effects of RRME as isolated from the pickled vegetables in Linxian County, a high incidence area of esophageal cancer, were studied in mice and rats. RRME alone did not cause tumor in the forestomach of mice and esophagus of rats. When the mice were intubated with a single dose of nitroso-sarcosine-ethylester (NSEE), the incidence of the forestomach carcinoma was only 9.5%. However, when the mice were given gastric doses of RRME after one single dose of NSEE, the incidence was increased to 41.0%. In rats, the tumor incidence was 5.3% in nitroso-methylbenzylamine (NMBzA) group, while in NMBzA kRME group, it was 20.7%. In rats intubated with NSEE for 7 times, no carcinoma appeared in esophageal epithelium; while followed by gastric doses of RRME, the incidence of esophagus carcinoma increased up to 63.2%. The experimental results show that RRME has distinct promoting effect on the process of cocarcinogenesis initiated by NSEE and NMBzA in the forestomach of mice and esophagus of rats, but without carcinogenic effect itself. Retinamide (RI) and massive dose of vitamin C showed an obviously inhibitory effect on promoting action of RRME in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Dimethylnitrosamine; Esophageal Neoplasms; Female; Mice; Nitroso Compounds; Rats; Rats, Inbred Strains; Stomach Neoplasms; Tretinoin

A total of 238 samples of 24-h urine were collected from inhabitants of high-risk (Lin-xian) and low-risk (Fan-xian) areas for esophageal cancer in northern China, according to three protocols: (a) from undosed subjects; (b) from subjects who had ingested 100 mg L-proline three times a day 1 h after each meal; and (c) from subjects in Lin-xian who had ingested 100 mg ascorbic acid together with 100 mg L-proline three times a day 1 h after each meal. As an index of individual exposure to N-nitroso compounds or their precursors, ingested in food and/or formed endogenously, the levels of four urinary N-nitrosamino acids and nitrate were determined. The amounts of N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, N-nitrososarcosine, and nitrate excreted in the 24-h urine of undosed subjects in Lin-xian were significantly higher than those in Fan-xian, indicating a higher exposure of the inhabitants in the high-risk area to N-nitroso compounds and their precursors. Ingestion of L-proline resulted in a marked increase in urinary N-nitrosoproline levels in inhabitants from both areas, suggesting that endogenous nitrosation may occur to a larger extent when appropriate amine precursors are ingested in foods. Intake of moderate doses of ascorbic acid by high-risk subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in the low-risk area. If N-nitroso compounds formed in vivo are among the causative factors for esophageal cancer in this area of northern China, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds, thus offering a rational basis for long-term intervention studies in this area.

Topics: Adult; Aged; Ascorbic Acid; China; Esophageal Neoplasms; Humans; Middle Aged; Nitrates; Nitrosamines; Risk

Topics: Animals; Ascorbic Acid; Esophageal Neoplasms; Liver Neoplasms; Male; Rats; Rats, Inbred Strains; Riboflavin; Riboflavin Deficiency

Biochemical analyses were conducted to evaluate the nutritional status of a high esophageal cancer risk population in Linxian, People's Republic of China. A study was conducted in September 1980 in which plasma levels of vitamins A, B2, and C were analyzed. In a second study in 1983, the plasma fat-soluble vitamins were analyzed with a newly developed high-performance liquid chromatography method that allowed the simultaneous determination of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, and lycopene in 0.1 ml of plasma sample. The average plasma retinol levels ranged from 24 to 27 micrograms/dl among the population groups, with 20-35% of the individuals having levels under 20 micrograms/dl. Low plasma beta-carotene levels averaging 8-12 micrograms/dl were observed among the population groups. Low plasma alpha-tocopherol levels with average values around 700 micrograms/dl were also observed; about half the individuals were either low or deficient in vitamin E. After 4 months of supplementation with daily multivitamin tablets, the plasma contents of retinol and alpha-tocopherol were significantly increased. The plasma alpha-carotene and beta-carotene were also increased, possibly as a reflection of seasonal changes in the diet or a sparing effect of vitamins A and E on these carotenes. Low plasma ascorbate levels with an average of 567 micrograms/dl were observed, and about 23% of the individuals had values under 200 micrograms/dl. Riboflavin deficiency was prevalent, with about 90% of the subjects having an erythrocyte glutathione activation coefficient over 1.2. The study establishes the low nutritional status in vitamins of the population in Linxian and provides the background for further studies on the effects of nutritional deficiency on carcinogenesis.

Topics: Adult; Aged; Ascorbic Acid; Carotenoids; China; Chromatography, High Pressure Liquid; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Riboflavin; Risk; Vitamin A; Vitamin A Deficiency; Vitamin E

As part of a pilot study to assess the feasibility of a long-term intervention trial to be done in Linxian, People's Republic of China, nutritional status and compliance were assessed in villagers taking daily multivitamin pills containing the U.S. Recommended Dietary Allowances (RDA). Before the start of the trial and again during its 4th month, nutritional status was assessed by laboratory tests and a dietary interview. Compliance was assessed in all subjects by pill counts and in a subset by urinary riboflavin loading-dose tests. At the outset of the trial, the study population had widespread biochemical and dietary deficiencies of ascorbic acid and riboflavin. As expected, subjects taking a daily pill had significantly improved status for these vitamins during the study. Compliance as measured by pill counts was excellent, with over 90% of the subjects taking at least 80% of their daily pills. Mean urinary excretion of a riboflavin loading dose entered and remained in the normal range after 3 weeks of supplementation, indicating that compliance did not fall off over time. Compliance was similar in normal subjects and in those with a prior diagnosis of esophageal dysplasia. Compliance also was nearly as good in subjects receiving monthly home visits as in those receiving weekly home visits from the barefoot doctor (village paramedical worker). The results of this pilot study indicated that a long-term intervention trial was feasible in Linxian and that the RDA dose level of vitamins was effective in ameliorating certain nutritional deficiencies prevalent in the study population.

Topics: Adult; Aged; Ascorbic Acid; China; Clinical Trials as Topic; Energy Intake; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Patient Compliance; Prospective Studies; Riboflavin; Vitamins

Topics: Alcohol Drinking; Ascorbic Acid; Beverages; Citrus; Esophageal Neoplasms; Female; France; Humans; Male; Risk

Topics: Ascorbic Acid; Dose-Response Relationship, Drug; Esophageal Neoplasms; Gastrointestinal Neoplasms; Humans; Kinetics; Nitrosamines; Nitroso Compounds; Precancerous Conditions; Proline; Risk; Thiazoles; Thiazolidines

The biological mode of action of tumor promoters, exemplified by the phorbol esters, is a subject of intensive study in a number of laboratories. A few investigators have recently begun to examine the role of dietary nutrients in tumor promotion, but the available data are sparse and interpretation difficult. A few examples are provided to indicate that some nutrients may be important in the promotion of cancer. However, the fine dividing line between effects on initiation or on promotion, so clearly shown in the mouse two-stage skin cancer model, is not so clear as yet in models used for studies in nutritional carcinogenesis. The animal models for these studies have been primarily rats, mice and hamsters. These have shown that nutrients which appear to have promotion activity are zinc deficiency and 13-cis-retinoic acid for the esophagus; vitamin A deficiency and lipotrope deficiency for the forestomach, unsaturated fat and vitamin A deficiency for liver and colon, lipotrope deficiency for the liver; selenium for the liver. It is probably more correct at this early stage of investigation to consider the effects of nutrients acting either during the time of exposure to the carcinogen, or, after such exposure and when no detectable carcinogen is found in the animals tissues, rather than as promoters in the strict sense.

Topics: Animals; Ascorbic Acid; Carcinogens; Cocarcinogenesis; Colonic Neoplasms; Cricetinae; Diet; Disease Models, Animal; Esophageal Neoplasms; Gastrointestinal Neoplasms; Liver Neoplasms; Mice; Neoplasms, Experimental; Pancreatic Neoplasms; Rats; Stomach Neoplasms; Zinc

The results of an epidemiological study using the case-control method on 150 oesophageal cancer cases, observed at the IIIrd Surgical Department in Padua and on 150 controls are presented. The results show that alcohol an maize flour (corn meal) are two aetiopathogenetic factors of verified statistical significance in oesophageal carcinoma in the Veneto population. This confirms other studies among populations with a high risk of oesophageal cancer.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; Ascorbic Acid Deficiency; Esophageal Neoplasms; Feeding Behavior; Female; Humans; Italy; Male; Middle Aged; Smoking; Vitamin A; Vitamin A Deficiency; Zea mays; Zinc

The long-term maintenances of guinea pigs on diets with (a) lack of vitamin C, (b) lack of lysine, methionine and threonine or (c) with a deficiency of all the above nutrients led to the development of oesophageal hyperplasia and atrophic gastritis. These dietary insufficiences were found to favour oesophageal and gastric cancer production by NPIP with a greatly shortened tumour induction time. It seems likely that the observed features of NPIP carcinogenesis depend on the alteration of the chemistry and biochemistry of these organs provoked by the low intake of the above-mentioned nutrients.

Topics: Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinogens; Esophageal Neoplasms; Female; Guinea Pigs; Male; Neoplasms, Experimental; Nitrosamines; Probability; Stomach Neoplasms

In order to examine the nutritional status of the population of Linxian (in Henan, China) known to be at high risk for esophageal cancer (EC), we analyzed blood samples and conducted 3-day dietary surveys on 3 groups of normal adults, age 40-50, from Henan province. Two groups were from Linxian, where the EC mortality rate is about 138/100,000 (Group C, consisting of volunteers with a family history of EC, and Group NC, consisting of those who did not have a family history of EC). The third group, Group F, was from Fanxian, where the EC mortality rate is about 24/100,000. The average plasma retinol level was found to be about 0.27 micrograms/ml in all 3 groups; about 13%-20% of the individuals had a level less than 0.2 micrograms/ml. The average plasma carotene level of all 3 groups appeared to be adequate, ranging from 0.5-1.0 micrograms/ml. About 23% of the subjects in both Groups C and NC had low (less than 2 micrograms/ml) plasma ascorbate levels; in Group F, 16% had low ascorbate levels. Less than 12% of the individuals in each of the 3 groups had erythrocyte glutathione reductase activation coefficients less than 1.2, indicating a widely occurring riboflavin deficiency. Consumption of alcoholic beverages was not found to be a contributing factor to EC. The results of the present study reveal a deficiency of vitamins in the study populations, but do not indicate that the average nutritional status of the volunteers in Group C was worse than that of Groups NC and F with regard to vitamin A, ascorbate, and riboflavin.

Topics: Adult; Alcohol Drinking; Ascorbic Acid; Avitaminosis; Carotenoids; China; Diet; Diet Surveys; Esophageal Neoplasms; Feeding Behavior; Female; Humans; Male; Middle Aged; Riboflavin; Risk; Vitamin A

The reported dietary, alcohol consumption and smoking habits of 147 Roswell Park Memorial Institute white male patients diagnosed with cancer of the esophagus were compared with the reports of 264 white males of comparable ages with diagnoses other than cancer. Overall frequency of vegetable an fruit consumption was associated with lower risk; persons reporting fruit and/or vegetable consumption 31-40 times a month had significantly greater risk than those who reported consumption 81 times a month or more. Calculated indexes of vitamin A and vitamin C intake were similarly related to reduction in risk. Dose-response gradients were observed for frequency of vegetable and/or fruit consumption, as well as for vitamin A and C intake. The putative protective effect of vegetable and fruit intake remained evident after controlling for its possible association with smoking and drinking. Previously reported associations of smoking, alcohol use and social class, as measured by type of occupation, were replicated in these data. The findings of this investigation in instances of colon, lung, bladder, oral, and laryngeal cancers, and with evidence of tumor inhibition by vegetable properties in animals. Interpretation of the findings is limited by the difficulties of retrospective assessment of dietary intake and by possible confounding by other factors known to be related to esophageal cancer.

Topics: Alcohol Drinking; Ascorbic Acid; Diet; Esophageal Neoplasms; Feeding Behavior; Fruit; Humans; Male; Meat; Occupational Medicine; Risk; Smoking; Vegetables; Vitamin A

Topics: Adult; Ascorbic Acid; Cardia; Esophageal Neoplasms; Female; Flavonoids; Humans; Middle Aged; Oxygen Inhalation Therapy; Stomach Neoplasms; Uterine Cervical Neoplasms; Vitamin B Complex; Vitamins

Topics: Animals; Ascorbic Acid; Chickens; China; Esophageal Neoplasms; Female; Humans; Male; Nitrosamines; Pharyngeal Neoplasms; Rats

Topics: Adenocarcinoma; Aged; Animals; Ascorbic Acid; Barium Sulfate; Cardia; Diet; Esophageal Neoplasms; Esophagogastric Junction; Female; Gastrectomy; Hematemesis; Humans; Jejunum; Male; Methods; Middle Aged; Milk; Physical Exertion; Physical Therapy Modalities; Radiography