beta-carotene and Esophageal-Neoplasms

dietary β-carotene and vitamin A intake have shown some potential effect in the development of esophageal cancer. This meta-analysis was performed to investigate the association of β-carotene and vitamin A intake on the risk of esophageal cancer.. the PubMed, Embase, Web of Science and Wanfang Med online databases were systematically searched to collect the relevant articles regarding the impact of β-carotene and vitamin A intake on esophageal cancer risk. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were combined using the Review Manager Version 5.3 software.. this meta-analysis included 14 articles. The highest category of β-carotene intake may significantly reduce the risk of esophageal cancer compared with the lowest category (OR = 0.62, 95 % CI = 0.50-0.77). Similar significant results were found in American and European populations but not in other populations with β-carotene intake. An inverse association was found between vitamin A intake and esophageal cancer risk (OR = 0.79, 95 % CI = 0.63-0.99). No potential publication bias was detected.. our study suggested that dietary β-carotene and vitamin A intake may reduce the risk of esophageal cancer. More relevant studies are needed to further explore this association, as there were some limitations in our analysis.

Topics: beta Carotene; Diet; Esophageal Neoplasms; Humans; Nutritional Status; Risk Factors; Vitamin A

Aspirin and other NSAIDs are showing promise in the chemoprevention of colorectal cancer. Ongoing trials will eventually provide still lacking information about the optimum dose and treatment duration. NSAIDs may also help to lower the risk of cancer in other organs such as the oesophagus, and possibly breast, stomach, and lung. The chemoprevention by NSAIDs should be seen not as the sole method of prevention, but as an additional tool which will be accompanied by other approaches such as stopping smoking, limiting alcohol consumption, and eating more fruits and vegetables. The chemoprevention by NSAIDs needs also to be balanced against the risks of toxicity (particularly in the stomach) and the other beneficial effects such as prevention of cardiovascular morbidity and mortality. Some of the NSAID induced gastric ulceration and bleeding will most likely be avoided by adopting the use of cyclooxygenase-2 (COX-2) selective NSAIDs, which will selectively inhibit COX-2 while sparing COX-1.

Topics: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Case-Control Studies; Child; Cohort Studies; Colorectal Neoplasms; Cricetinae; Cyclooxygenase Inhibitors; Esophageal Neoplasms; Humans; Neoplasms; Pancreatic Neoplasms; Prospective Studies; Prostaglandin Antagonists; Prostaglandins; Randomized Controlled Trials as Topic; Skin Neoplasms; Stomach Neoplasms; Time Factors

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Esophageal Neoplasms; Fruit; Humans; Lung Neoplasms; Male; Neoplasms; Risk Factors; Stomach Neoplasms; Vegetables; Vitamins

Previous studies have found associations between one-carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed prediagnostic serum concentrations of several one-carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin and homocysteine) in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case-control study including 127 noncardia gastric adenocarcinoma (NCGA), 41 esophagogastric junctional adenocarcinoma and 60 esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow-up time. One-carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of NCGA (95% CI = 2.7-12.6 for lowest compared to highest quartile, p-trend <0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population. As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen.

Topics: Aged; alpha-Tocopherol; beta Carotene; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Supplements; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Finland; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Prospective Studies; Riboflavin; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency

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

To examine whether vitamin/mineral supplementation may lower mortality and incidence from human cancer and mortality from other diseases as well as to provide the scientific basis and feasible approach for human cancer prevention and control, between 1982-1991 scientists from China and USA conducted two randomized, double-blind, and placebo-controlled nutrition intervention trials in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population's chronic deficiencies of multiple nutrients are etiologically involved. In the first trial, the Dysplasia Trial, 3,318 individuals with a cytologic diagnosis of esophageal dysplasia received daily 26 vitamin/mineral supplements or placebos for 6 years; The second trial, the General Population Trial, involved 29,584 individuals and used an one-half replicate of a 2(4) fractional factorial design which randomized to 8 groups for testing the effects of daily supplementation of 4 different vitamin/mineral combinations and placebo for a period of 5 1/4 years. Compliance assessed by monthly pill counts and quarterly monitoring of biochemical assays indicated that the participant compliance was excellent. As endpoints of the trials, incident cancers and deaths were identified through all medical facilities in local areas, supplemented by special endoscopy and cytology examinations, and confirmed by 3-level review groups. A total of 323 deaths occurred during 6 year period among participants in the dysplasia trial, and 2,127 deaths from the general population trial during 5 1/4 years. Besides, an eye examination, which included detailed lens evaluations, was included in the extensive re-examination protocol to ascertain whether use of the supplements had affected the risk of developing age-related cataracts among participants in the two trials. Results from Dysplasia Trial indicated that after 6 years of daily supplementation with multiple vitamins and minerals, total mortality among those in the active treatment group was slightly (9%) lower than in the placebo group; and deaths of esophageal cancer also declined by 17%, as well as a sizeable reduction in cerebrovascular disease mortality (near 40%) was seen, though none was statistically significant. However, intervention had decreased prevalence of eye nuclear cataract (43%) (P < 0.01). The findings from the General Population Trial provide support for the hypothesis that intake

Topics: Adult; Aged; beta Carotene; Carotenoids; Cataract; Cerebrovascular Disorders; China; Double-Blind Method; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Niacin; Precancerous Conditions; Prevalence; Riboflavin; Selenium; Stomach Neoplasms; Vitamin E

This intervention trial carried out in Uzbekistan (former USSR) in an area with a high incidence of oral and esophageal cancer involved random allocation of 532 men, 50 to 69 years old, with oral leukoplakia and/or chronic esophagitis to one of four arms in a double-blind, two-by-two factorial design, with active arms defined by the administration of (a) riboflavin; (b) a combination of retinol, beta-carotene, and vitamin E; or (c) both. Weekly doses were 100,000 IU of retinol, 80 mg of vitamin E, and 80 mg of riboflavin. The dose of beta-carotene was 40 mg/d. Men in the trial were followed for 20 months after randomization. The aim of the trial was to determine whether treatment with these vitamins or their combination could affect the prevalence of oral leukoplakia and/or protect against progression of oral leukoplakia and esophagitis, conditions considered to be precursors of cancer of the mouth and esophagus. A significant decrease in the prevalence odds ratio (OR) of oral leukoplakia was observed after 6 months of treatment in men receiving retinol, beta-carotene, and vitamin E (OR = 0.62; 95% confidence interval (CI): 0.39 to 0.98). After 20 months of treatment, no effect of vitamin supplementation was seen when the changes in chronic esophagitis were compared in the four different treatment groups, although the risk of progression of chronic esophagitis was lower in the subjects allocated to receive retinol, beta-carotene and vitamin E (OR = 0.65; 95% CI: 0.29 to 1.48) A secondary analysis not based on the randomized design revealed a decrease in the prevalence of oral leukoplakia in men with medium (OR = 0.45; 95% CI: 0.21 to 0.96) and high (OR = 0.59; 95% CI: 0.29 to 1.20) blood concentrations of beta-carotene after 20 months of treatment. Risk of progression of chronic esophagitis was also lower in men with a high blood concentration of beta-carotene, odds ratios being 0.30 (95% CI: 0.10 to 0.89) and 0.49 (95% CI: 0.15 to 1.58) for medium and high levels, respectively. A decrease in risk, also statistically not significant, was observed for high vitamin E levels (OR = 0.39; 95% CI: 0.14 to 1.10). These results were based on levels of vitamins in blood drawn after 20 months of treatment.

Topics: Aged; beta Carotene; Carotenoids; Chronic Disease; Double-Blind Method; Esophageal Neoplasms; Esophagitis; Humans; Incidence; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Odds Ratio; Precancerous Conditions; Prevalence; Riboflavin; Risk Factors; Uzbekistan; Vitamin A; Vitamin E; Vitamins

Topics: Aged; beta Carotene; Carotenoids; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Esophageal Neoplasms; Esophagitis; Humans; Male; Middle Aged; Placebos; Precancerous Conditions; Riboflavin; Vitamin A

β-carotene, a type of terpenoid, has many metabolic and physiological functions. In particular, β-carotene has an antitumor effect. However, the efficacy of β-carotene against esophageal squamous cell carcinoma (ESCC) remains unclear. In our study, β-carotene inhibited the growth of ESCC cells and downregulated expression of the Caveolin-1 (Cav-1) protein. Cav-1 protein was expressed only in ESCC cells, not in Het-1A cells. Moreover, β-carotene triggered apoptosis, induced cell cycle G0⁄G1 phase arrest, and inhibited cell migration. To explore the mechanism involved in these processes, we further examined the effect of β-carotene on the Cav-1-mediated AKT/NF-κB pathway. The results showed that the level of AKT and NF-κB phosphorylation was dramatically inhibited, which led to an increase in the Bax/Bcl-2 ratio. Correspondingly, the activity of Caspase-3 was also enhanced. These data suggest that β-carotene has an antiproliferative role in ESCC cells and may be a promising chemotherapeutic agent for use against ESCC cells.

Topics: Apoptosis; beta Carotene; Carcinoma, Squamous Cell; Caveolin 1; Cell Line, Tumor; Esophageal Neoplasms; Humans; NF-kappa B; Proto-Oncogene Proteins c-akt; Signal Transduction

Recently, we reported that β-carotene exhibited anticancer activity against human esophageal squamous cell carcinoma cells in vitro. In the present study, we examined a novel therapeutic strategy by combining β-carotene with 5-fluorouracil (5-FU) in human esophageal cancer in vitro and in vivo, and elucidated the underlying mechanisms. We found that the combination of 5-FU and β-carotene displayed greater growth inhibitory effects than did either compound alone in esophageal squamous cell carcinoma (ESCC) cells. In addition, the combination of 5-FU and β-carotene displayed greater tumor growth inhibition in an Eca109 xenograft mouse model than did a single agent with low systemic toxicity. β-Carotene enhanced 5-FU-induced apoptosis. TUNEL staining revealed that the rate of TUNEL-positive cells was markedly increased in tumor tissues after treatment with 5-FU and β-carotene. Western blotting and immunohistochemistry revealed the down-regulation of Bcl-2 and PCNA and the up-regulation of Bax and caspase-3 in tumor tissues. Further studies demonstrated that the combined administration of 5-FU and β-carotene significantly down-regulated the protein levels of Cav-1, p-AKT, p-NF-κB, p-mTOR and p-p70S6K in Eca109 cells more effectively than did 5-FU alone. These data suggested that the combined therapy of 5-FU and β-carotene exerted synergistic antitumor effects in vivo and in vitro and could constitute a novel therapeutic treatment for ESCC.

Topics: Animals; Antineoplastic Agents; Apoptosis; beta Carotene; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Drug Therapy, Combination; Esophageal Neoplasms; Fluorouracil; Humans; Mice; Neoplasms, Experimental

The aim was to evaluate roles of vitamin D3 (VD3) and beta-carotene (BC) in the development of esophageal squamous cell carcinoma (ESCC) in a high-risk area, Huai'an District, Huai'an City, China.. 100 new ESCC diagnosed cases from 2007 to 2008 and 200 residency- age-, and sex-matched healthy controls were recruited. Data were collected from questionnaires, including a food frequency questionnaire (FFQ) to calculate the BC intake, and reversed phase high-performance liquid chromatography (RP-HPLC) was used to measure the serum concentrations of BC and VD3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in conditional logistic regression models.. The average dietary intake of BC was 3322.9 μg (2032.4- 5734.3) in the case group and 3626.8 μg (1961.9-5827.9) in control group per capita per day with no significant difference by Wilcoxon test (p>0.05). However, the levels of VD3 and BC in the case group were significantly lower than in the control group (p<0.05). The OR values of the highest quartile and the lowest quartile of VD3 and BC in serum samples were both 0.13.. Our results add to the evidence that high circulating levels of VD3 and BC are associated with a reduced risk of ESCC in this Chinese population.

Topics: beta Carotene; Carcinoma, Squamous Cell; Case-Control Studies; China; Cholecalciferol; Chromatography, High Pressure Liquid; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Risk Factors

This paper discusses the different stages of normal esophageal's developing to esophageal cancer, and the difference among dietary patterns of patients with esophageal cancer and acceptable daily intake of vitamin A, E and beta carotene intake in diet. This paper takes advantage of food composition table, calculates the intake amount of dietary vitamin A, E and beta carotene in all kinds of food for patients with esophageal cancer, and analyzes the intake amount difference of dietary vitamin A, E and beta carotene in each kind of food for different groups of people. Research conclusions: the low content level of dietary vitamin A, E beta-carotene and low intake amount of beans, vegetables and fruit intake may increase the risk of esophageal cancer' occurring, while the relationship among dietary vitamin E, the occurrence and development of esophageal cancer needs further discussion.

Topics: Animals; beta Carotene; Diet; Esophageal Neoplasms; Humans; Male; Neoplasm Staging; Rats; Rats, Sprague-Dawley; Vitamin A; Vitamin E

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

Esophageal cancer is a common malignant tumor occurring in human esophageal epithelial tissue. The primary purpose of this paper was to define the effects of β-carotene and 1,25-dihydroxyvitamin D3, alone and in combination, on cell proliferation, cell cycle and apoptosis of human esophageal cancer EC9706 cells. Treatment with different concentrations of β-carotene and/or 1,25-dihydroxyvitamin D3. MTT assay showed that β-carotene and 1,25-dihydroxyvitamin D3 significantly inhibited proliferation of EC9706 cells in a dose- and time-dependent manner. Further studies also demonstrated that β-carotene alone or 1,25-dihydroxyvitamin D3 alone caused a marked increase on the induction of apoptosis in EC9706 cells. The percentage of G0/G1-phase cells significantly increased on addition of 1,25-dihydroxyvitamin D3 alone, but there were no significant changes with β-carotene alone. These two agents in combination synergistically inhibited cell growth and induced apoptosis. Therefore, our results indicate that β-carotene and 1,25-dihydroxyvitamin D3 in combination may provide a novel strategy for preventing and treating esophageal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; beta Carotene; Calcitriol; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Esophageal Neoplasms; Humans

Although Iran is a high-risk region for esophageal squamous cell carcinoma (ESCC), dietary factors that may contribute to this high incidence have not been thoroughly studied. The aim of this study was to evaluate the effect of macronutrients, vitamins and minerals on the risk of ESCC.. In this hospital-based case-control study, 47 cases with incident ESCC and 96 controls were interviewed and usual dietary intakes were collected using a validated food frequency questionnaire. Data were modeled through unconditional multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), controlling for age, sex, gastrointestinal reflux, body mass index, smoking history (status, intensity and duration), physical activity, and education.. ESCC cases consumed significantly more hot foods and beverages and fried and barbecued meals, compared to the controls (p < 0.05). After adjusting for potential confounders, the risk of ESCC increased significantly in the highest tertiles of saturated fat [OR:2.88,95%CI:1.15-3.08], cholesterol [OR:1.53, 95%CI: 1.41-4.13], discretionary calorie [OR:1.51, 95%CI: 1.06-3.84], sodium [OR:1.49,95%CI:1.12-2.89] and total fat intakes [OR:1.48, 95%CI:1.09-3.04]. In contrast, being in the highest tertile of carbohydrate, dietary fiber and (n-3) fatty acid intake reduced the ESCC risk by 78%, 71% and 68%, respectively. The most cancer-protective effect was observed for the combination of high folate and vitamin E intakes (OR: 0.02, 95%CI: 0.00-0.87; p < 0.001). Controls consumed 623.5 times higher selenium, 5.48 times as much β-carotene and 1.98 times as much α-tocopherol as the amount ESCC cases consumed.. This study suggests that high intake of nutrients primarily found in plant-based foods is associated with a reduced esophageal cancer risk. Some nutrients such as folate, vitamin E and selenium might play major roles in the etiology of ESCC and their status may eventually be used as an epidemiological marker for esophageal cancer in Iran, and perhaps other high-risk regions.

Topics: Aged; alpha-Tocopherol; beta Carotene; Carcinoma, Squamous Cell; Case-Control Studies; Confidence Intervals; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Energy Intake; Esophageal Neoplasms; Feeding Behavior; Female; Folic Acid; Hospitalization; Humans; Incidence; Interviews as Topic; Iran; Logistic Models; Male; Micronutrients; Middle Aged; Odds Ratio; Pilot Projects; Risk Factors; Selenium; Surveys and Questionnaires; Vitamin E; Vitamins

Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved.. We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).. Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24).. These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect.. Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC.

Topics: Aged; alpha-Tocopherol; Atrophy; beta Carotene; Biomarkers; Carcinoma, Squamous Cell; Case-Control Studies; Esophageal Neoplasms; Finland; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Randomized Controlled Trials as Topic; Risk; Smoking; Stomach

To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers.. The changes in serum levels of retinoids (vitamin A, alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in matched groups) for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used.. The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer.. Retinoids (as environmental factors) are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.

Topics: Adult; Aged; beta Carotene; Colorectal Neoplasms; Esophageal Neoplasms; Factor V; Female; Humans; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Point Mutation; Retinoids; Stomach Neoplasms; Vitamin A; Xanthophylls; Zeaxanthins

Participants in the General Population Trial, a randomized nutrition intervention trial in Linxian, China, who received a combination of selenium, beta-carotene, and vitamin E supplements, had statistically significantly lower cancer mortality rates than those who did not receive the supplements. In the current study, we used a case-cohort design to examine the association between pre-trial serum vitamin E levels and the risks of developing esophageal and gastric cancers during the trial. We measured serum alpha- and gamma-tocopherol and cholesterol levels in 1072 case patients with incident esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), or gastric noncardia cancer (GNCC) and in 1053 control subjects. The relative risks for comparisons of the highest to the lowest quartiles of serum alpha-tocopherol were 0.63 (95% confidence interval [CI] = 0.44 to 0.91) for ESCC, 0.84 (95% CI = 0.55 to 1.26) for GCC, and 2.05 (95% CI = 0.89 to 4.75) for GNCC. Serum gamma-tocopherol level was not associated with the incidence of any of these cancers. Our findings provide support for the role of alpha-tocopherol in the etiology of upper gastrointestinal cancers.

Topics: Adult; Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Cardia; Case-Control Studies; China; Confidence Intervals; Dietary Supplements; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; Stomach Neoplasms; Vitamin E

This study examined the relationship between pretrial serum concentrations of retinol, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer.. We used a stratified case-cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models.. Median values in our cohort were low for serum retinol (33.6 microg/dl), beta-carotene (4.3 microg/dl), and beta-cryptoxanthin (3.5 microg/dl), but were high for lutein/zeaxanthin (40.0 microg/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83-0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63-0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31-0.96). For beta-cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76-1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0-1.3) with increasing concentration of serum lutein/zeaxanthin.. In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma, Squamous Cell; China; Cryptoxanthins; Esophageal Neoplasms; Female; Humans; Lutein; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Regression Analysis; Risk Factors; Stomach Neoplasms; Vitamin A; Xanthophylls; Zeaxanthins

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 inhibitory effects of the newly-developed forms of beta-carotene--water-soluble and liposomal--have been studied in rats and mice bearing tumors induced in 4 models of carcinogenesis. Mammary tumors were induced by single injections of 1 mg methylnitrosourea into each gland. Esophageal tumors were induced in male rats by intragastric administration of 3 mg/kg methylbenzylnitrosoamine, thrice a week for 4 weeks. Tumors of the vagina and cervix uteri were induced by intravaginal painting with 25 mkg dimethylbenz(a)anthracene, twice a week for 6 weeks. Tumors of the lung were induced in female mice by intraperitoneal injection of 1 g/kg urethane, once a week for 6 weeks. With models I-III, animals received water-soluble beta-carotene (Aquiton-10) with drinking water (200 mg/I), on completion of carcinogen treatment and for another 9-12 months until the end of experiment. Urethane-treated mice received liposomal beta-carotene with drinking water (60 mg/l) 10 days before the beginning of carcinogen treatment and for another 6 months until the end experiment. Water-soluble beta-carotene failed to influence the carcinogenesis in the mammary gland and esophagus in rats; however, it significantly inhibited carcinoma development in murine vagina and cervix uteri (47.0%). Liposomal beta-carotene significantly inhibited lung adenomas (46.4%) and mammary carcinomas (55.6%) in urethane-treated mice.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Esophageal Neoplasms; Female; Liposomes; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Neoplasms, Experimental; Rats; Solubility; Uterine Cervical Neoplasms; Vaginal Neoplasms; Water

After early rises, oesophageal cancer mortality rates have tended to level off in Italy over the last two decades, and are now intermediate on a European scale (4.7/100000 males, 0.8/100000 females, world standard). This reflects the trends in consumption of the major risk factors for the disease, tobacco and alcohol, particularly in men. Within Italy, there is also a substantial variation in oesophageal cancer rates, with high mortality areas in the North-East of the country. On the basis of a case-control study conducted in northern Italy, the relative risk (RR) of the disease was 4.3 in heavy smokers and 3.5 in heavy drinkers. A diet poor in fresh fruit and vegetables was also related to the risk of the disease (RR = 2.5). In terms of population attributable risk, 71% of cases in men and 32% in women were accounted for tobacco smoking, 45% in males and 10% in females by alcohol drinking, 40% in men and 29% in women by a diet poor in fresh fruit and vegetables (and hence in beta-carotene). These three factors together accounted for 90% of cases in Italian men, and 58% in women (83% in both sexes combined).

Topics: Adult; Alcohol Drinking; beta Carotene; Case-Control Studies; Comorbidity; Diet; Esophageal Neoplasms; Europe; Female; Humans; Italy; Male; Middle Aged; Risk; Risk Factors; Smoking

The aim of this paper was to evaluate the combined effect of alcohol, smoking habits and frequency of consumption of selected dietary items, which are the major sources of retinoids and beta-carotene in the Italian diet, on the risk of esophageal cancer (EC). The adequacy of the multiplicative structure for describing the effect of these factors on risk was examined. The analysis was carried out using the Breslow and Storer family of relative risk functions to assess which scale, between the subadditive and the supermultiplicative, could better explain the risk structure underlying the data. Data from a case-control study including 211 males with EC and 712 controls were analyzed. Data were collected in teaching and general hospitals of the greater Milan area (Italy). Under the multiplicative model, consistent with the results obtained in other studies, alcohol and tobacco consumption increased the risk of EC. There was no significant association between the retinol index and the risk of EC, while the beta-carotene index showed a protective effect. Using the Breslow and Storer family it was possible to rule out the additive model as an adequate one to describe the relative risk. The results suggest that the combined effect of alcohol, smoking and beta-carotene intake is near to multiplicative. A larger data set and perhaps more detailed data on risk factors are needed to discriminate among models near the multiplicative one. Important implications on causal interpretation and public health practice may derive from this type of analysis.

Topics: Adult; Aged; Alcohol Drinking; beta Carotene; Carotenoids; Case-Control Studies; Diet; Esophageal Neoplasms; Humans; Logistic Models; Male; Middle Aged; Risk; Risk Factors; Smoking; Vitamin A

The population attributable risk for oesophageal cancer in relation to cigarette smoking, elevated alcohol use and low beta-carotene intake has been estimated with 300 cases and 1203 controls in Greater Milan. In males 71% of oesophageal cancers were attributable to smoking, 45% to elevated alcohol use and 40% to low beta-carotene consumption. The corresponding figures were 32%, 10% and 29% in females and 61%, 39% and 38% in total. The overall estimate, including the joint effect of the three factors, was 90% in males, 58% in females and 83% in total. The discrepancies between the sums are due to the assumption of a multiplicative model and to the great percentage of oesophageal cancers attributable to each single factor. Cigarette smoking is the major known cause of oesophageal cancer and the three factors account for practically all the difference between male and female mortality rates. Elimination of smoking, reduction of alcohol consumption and enrichment of diet with fruit and vegetables would make oesophageal cancer a rare disease in Italians of both sexes.

Topics: Adult; Aged; Alcohol Drinking; beta Carotene; Carotenoids; Case-Control Studies; Diet; Esophageal Neoplasms; Female; Humans; Italy; Male; Middle Aged; Risk Factors; Smoking

Topics: beta Carotene; Carotenoids; Esophageal Neoplasms; Esophagus; Humans; Precancerous Conditions; Riboflavin; Vitamin A

Plasma levels of nutrients in 196 individuals were assayed as part of a study of the feasibility of a nutrition intervention trial in Linxian, a county in North Central China with exceptionally high rates of esophageal cancer. High-performance liquid chromatography analyses of samples collected in April 1983 showed low (relative to United States standards) base-line levels for retinol, alpha-tocopherol, and beta- and alpha-carotene. Repeat sampling in August 1983 revealed significantly increased plasma levels of retinol and alpha-tocopherol among those who had in the interim received daily supplementation with multivitamin pills containing the Recommended Dietary Allowance levels of those nutrients but not among those without supplementation. Levels of carotenes, which were not included in the pills, tended to increase regardless of supplementation, consistent with seasonal variations in availability of carotenoid-containing foods. Atomic absorption spectrophotometry analyses showed essentially normal levels of copper and zinc in plasma. Neither was affected by vitamin supplementation (the pills did not contain minerals) nor seasonal variation. The data are generally consistent with prior biochemical surveys in indicating marginal or low status of several nutrients in Linxian and in showing that supplementation with vitamins can effectively raise blood nutrient levels.

Topics: Adult; Aged; beta Carotene; Carotenoids; China; Esophageal Neoplasms; Humans; Middle Aged; Nutritional Physiological Phenomena; Patient Compliance; Risk; Vitamin A; Vitamin E; Vitamins