ascorbic-acid and Digestive-System-Neoplasms

Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian randomization (MR) study. Single nucleotide polymorphisms of diet-derived circulating antioxidants (i.e., α- and γ-tocopherol, ascorbate, retinol, β-carotene, lycopene, and urate), accessed by absolute levels and relative metabolite concentrations, were used as genetic instruments. Summary statistics for digestive system cancers were obtained from the UK Biobank and FinnGen studies. Two-sample MR analyses were performed in each of the two outcome databases, followed by a meta-analysis. The inverse-variance weighted MR was adopted as the primary analysis. Five additional MR methods (likelihood-based MR, MR-Egger, weighted median, penalized weighted median, and MR-PRESSO) and replicate MR analyses for outcomes from different sources were used as sensitivity analyses. Genetically determined antioxidants were not significantly associated with five digestive system cancers, after correcting for multiple tests. However, we found suggestive evidence that absolute ascorbate levels were negatively associated with colon cancer in UK Biobank-the odds ratio (OR) per unit increase in ascorbate was 0.774 (95% confidence interval [CI] 0.608-0.985,

Topics: Antioxidants; Ascorbic Acid; Colonic Neoplasms; Diet; Digestive System Neoplasms; Food; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; United Kingdom; Vitamin A

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

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

Previous observational case-control studies have shown significant controversy over the impact of dietary intake-related circulating antioxidants on the risk of digestive system tumors. We conducted a two-sample Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between increased levels of circulating antioxidants and digestive system tumors. Our circulating antioxidants (vitamin C, carotenoids, vitamin A, and vitamin E) were derived from absolute circulating antioxidants and circulating antioxidant metabolites, and their corresponding instrumental variables were screened from published studies. The digestive system tumors we studied included colorectal, gastric, pancreatic, liver, and esophageal cancer, and the corresponding summary GAWS (genome-wide association study) data were obtained from the UK Biobank database. We first evaluated the causal relationship between each tumor and circulating antioxidants and then used meta-analysis to summarize the results of MR analysis of different tumors. No significant associations were noted for genetically predicted circulating antioxidants and higher risk of digestive system tumors in our study. The pooled ORs (odds ratio) are 0.72 (95% CI: 0.46-1.11; β-carotene), 0.93 (95% CI: 0.81-1.08; lycopene), 2.12 (95% CI: 0.31-14.66; retinol), and 0.99 (95% CI: 0.96-1.02; ascorbate) for absolute circulating antioxidants; for circulating antioxidant metabolites, the pooled ORs for digestive system tumors risk per unit increase of antioxidants were 1.29 (95% CI: 0.39-4.28; α-tocopherol), 1.72 (95% CI: 0.85-3.49; γ-tocopherol), 1.05 (95% CI: 0.96-1.14; retinol), and 1.21 (95% CI: 0.97-1.51; ascorbate), respectively. Our study suggested that increased levels of dietary-derived circulating antioxidants did not reduce the risk of digestive system tumors.

Topics: Antioxidants; Ascorbic Acid; Diet; Digestive System Neoplasms; Gastrointestinal Neoplasms; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Risk Factors; Vitamin A

Experimental studies suggest beneficial effects of antioxidants in digestive cancer prevention. However, epidemiological results are contrasting and few studies quantitatively assessed supplemental intake. This study aimed at investigating the associations between antioxidant intakes (dietary, supplemental and total) and digestive cancer risk. This prospective study included 38 812 middle-aged subjects (≥45 years) from the NutriNet-Santé cohort (2009-2016). Dietary data were collected using repeated 24 h records. A specific questionnaire assessed dietary supplement use over a 12-month period. A composition database of about 8000 dietary supplements was developed. Associations between continuous and sex-specific quartiles of vitamins C and E, β-carotene and Se intakes and digestive cancer risk were characterised using multivariable Cox proportional hazard models. A total of 167 incident digestive cancers (120 colorectal, twenty-six pancreatic, nine oesophagus, seven stomach and five liver) were diagnosed during follow-up investigation. Dietary (hazard ratios (HR)Q4 v. Q1=0·56; 95 % CI 0·34, 0·91, P trend=0·01) and total (HRQ4 v. Q1=0·51; 95 % CI 0·30, 0·84, P trend=0·008) vitamin C intakes, dietary (HRQ4 v. Q1=0·56; 95 % CI 0·34, 0·92, P trend=0·005) and total (HRQ4 v. Q1=0·58; 95 % CI 0·36, 0·94, P trend=0·003) vitamin E intakes, and dietary (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·85, 1·00, P=0·04) and total (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·86, 0·99, P=0·03) Se intakes were associated with a decreased digestive cancer risk. Statistically significant interactions were observed between dietary and total Se intakes and alcohol consumption as well as between total vitamin E intake and smoking status. This prospective cohort study with quantitative assessment of supplemental intakes suggests a potential protective effect of several antioxidants (vitamins C and E and Se) on digestive cancer risk, and a modulation of some of these relationships by alcohol consumption and smoking status.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Diet; Dietary Supplements; Digestive System Neoplasms; Female; Humans; Male; Middle Aged; Multivariate Analysis; Nutrition Assessment; Proportional Hazards Models; Prospective Studies; Risk Factors; Selenium; Surveys and Questionnaires; Vitamin E

We examined the association between whole-grain intake and incident upper aerodigestive tract cancer in a cohort of 34,651 postmenopausal, initially cancer-free women. We also studied established risk factors for upper aerodigestive cancers, including fruit and vegetable intake, smoking and alcohol intake. A mailed questionnaire at baseline in 1986 included a food-frequency questionnaire and assessment of other cancer risk factors. During the 14-year follow-up period, 169 women developed cancer of the upper aerodigestive tract. For all upper aerodigestive cancers together, significant inverse associations were observed for the highest compared to the lowest tertile of whole grains [relative risk (RR) = 0.53, 95% confidence interval (CI) 0.34-0.81] and yellow/orange vegetables (RR = 0.58, 95% CI 0.39-0.87). In addition, those in the highest compared to lowest tertile of fiber intake from whole grain were less likely to develop upper aerodigestive tract cancer (RR = 0.56, 95% CI 0.37-0.84); fiber intake from refined grain was not significantly associated with upper aerodigestive tract cancer. Findings were generally similar for oropharyngeal (n = 53), laryngeal (n = 21), nasopharyngeal/salivary (n = 18), esophageal (n = 21) and gastric (n = 56) cancers, though numbers of cases were too small for statistical testing within individual cancers. These findings confirm previous observations that high intake of fruits and vegetables and that intake of whole grains and the fiber derived from them may reduce risk of upper aerodigestive tract cancers.

Topics: Aged; Alcohol Drinking; Ascorbic Acid; Carotenoids; Diet; Diet Records; Dietary Fiber; Digestive System Neoplasms; Edible Grain; Energy Intake; Female; Fruit; Humans; Middle Aged; Postmenopause; Respiratory Tract Neoplasms; Risk Factors; Surveys and Questionnaires; Vegetables; Vitamin A; Vitamin E

The aim of the present study was to elucidate the influence of social, dietary and environmental factors on the incidence of malignant epithelial tumours in the upper digestive tract and on the prognosis of patients with these cancers.. A population-based case-control study was carried out, and the patients in the study were included in a survival analysis.. The study was carried out at the Department of Otorhinolaryngology at Ullevål University Hospital, Oslo, Norway.. In the case-control study, 84 patients and 89 controls were included. Only the patients were included in the survival analysis.. Smoking showed the highest odds ratio (OR) for morbidity (OR = 29). The patients had in general a lower social status, and a higher alcohol intake (OR = 6.6). For both beta-carotene and vitamin C, the ORs decreased with increasing intake (OR = 0.2 and 0.3, respectively). Increased ORs were associated with low values for haemoglobin, iron, TIBC, folic acid, magnesium and especially for albumin (OR = 14), and with high values for ferritin, vitamin B12 and thiocyanate (a marker for smoking). Stage of the disease was an important prognostic factor. The relative risk (RR) of dying for disseminated vs localised tumours being 3.2. A poorer prognosis was linked to higher age, to smoking vs no smoking (RR = 2.3), and to lower levels of haemoglobin, albumin, magnesium and thiocyanate.. Strong beer, liquor, consumption of milk and table fat, low social status and smoking seemed to have a negative impact on both disease and survival. Fruit and vegetables might, however, reduce the risk. Whereas low serum albumin, iron and magnesium indicated a high OR for cancer, vitamin C and beta-carotene had the opposite implication. No significant implications on survival could be detected in blood chemistry beyond the stage of disease.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; beta Carotene; Carcinoma; Case-Control Studies; Diet; Dietary Fats; Digestive System Neoplasms; Female; Humans; Male; Middle Aged; Norway; Prognosis; Smoking; Social Class; Survival Analysis

We investigated whether the consumption of fruit and vegetables lowered cancer mortality in a cohort of 2112 Welsh men ages 45-69 years (The Caerphilly Study), which was followed-up for 13.8 years. At baseline (between 1979 and 1983), participants completed a 56-item food frequency questionnaire from which the consumption of fruit and vegetables was calculated. Relative risks (RR) were estimated with Cox proportional hazard analysis, with death from various types of cancer as a dependent variable, and fruit, vegetables, vitamin C, beta-carotene, dietary fiber, and potential confounders as independent variables. Mean consumption of vegetables and fruit at baseline was 118 g/day and 83 g/day, respectively. During follow-up 114 men died from cancer, including 51 men who died from respiratory tract cancer and 45 men who died from digestive tract cancer. Fruit consumption and the intake of dietary fiber were inversely related to respiratory tract cancer, but after adjustment for potential confounders including age, smoking, and social class, the association with fruit consumption became nonsignificant. Vegetable and fruit consumption was, independently from other risk factors, inversely related to mortality from cancer of the digestive tract (P for trend = 0.021), mainly due to an inverse association with fruit consumption (RR for the highest quartile versus the lowest was 0.3; 95% CI, 0.1-0.8). Vitamin C, beta-carotene, and dietary fiber were not significantly associated with cancers of the digestive tract. Vegetable and fruit consumption was also inversely related to all-cause cancer mortality, and the strongest association was observed for fruit consumption (RR in the highest versus lowest quartile was 0.5; 95% CI, 0.3-1.0). Consumption of vegetables and particularly the consumption of fruit could considerably lower the risk of dying from cancer in middle-aged men.

Topics: Age Factors; Antioxidants; Ascorbic Acid; beta Carotene; Cause of Death; Cohort Studies; Confounding Factors, Epidemiologic; Diet; Dietary Fiber; Digestive System Neoplasms; Feeding Behavior; Follow-Up Studies; Fruit; Humans; Longitudinal Studies; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Respiratory Tract Neoplasms; Risk Factors; Smoking; Social Class; Vegetables; Wales