Source-specific effects of micronutrients in lung cancer prevention.
ABSTRACT The role of micronutrients in lung cancer prevention is controversial, as observational and experimental studies have generated contradicting results. These discrepancies between studies may be due to different effects of micronutrients depending on source (diet or supplements). The objective of this study was to evaluate the association between vitamin C, E, folate and beta-carotene and lung cancer risk while focusing on source-specific effects of dietary and supplemental intake. The association was evaluated in a cohort of 55,557 Danes who completed a food frequency questionnaire including information on consumption of vitamin C, E, folate and beta-carotene from diet and supplements. Incidence rate ratios of lung cancer were calculated using Cox proportional hazards models. During a median follow-up of 10.6 years, 721 incident lung cancer cases were diagnosed. We found a significant protective effect of dietary vitamin E intake and a significantly higher lung cancer risk with supplemental beta-carotene and dietary folate intake. All three micronutrients exhibited significant source-specific effects. The harmful effect of dietary folate is, however, most likely to be due to uncontrolled confounding. Our results indicate source-specific effects of vitamin E and beta-carotene in lung cancer prevention with a preventive effect of dietary vitamin E and a harmful effect of supplemental beta-carotene. Future studies on micronutrients and lung cancer should take source into account.
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ABSTRACT: Few studies have considered source-specific micronutrient intake in relation to mortality under the consideration that dietary and supplemental intake could exhibit different effects. To evaluate the association between intake of vitamin C, E, folate, beta-carotene from diet and supplements, and overall mortality. Furthermore, to examine effect modification by smoking, alcohol intake, and BMI and to investigate if the effect of supplement use differs with dietary micronutrient intake. In a prospective cohort study of 55,453 middle-aged Danes, information regarding diet, supplement use, and lifestyle was collected through questionnaires. During follow-up, 6,767 deaths were identified and incidence rate ratios (IRRs) of mortality related to micronutrient intake were calculated using Cox proportional hazards models. The present study found no effect of dietary vitamin C, E, folate, or beta-carotene in relation to mortality. In contrast, supplemental folic acid was associated with a significantly increased mortality, whereas no other micronutrient supplement was associated with mortality. Effect modification by smoking and alcohol intake, but not BMI, was suggested in relation to some dietary micronutrients. The effect of supplements did not differ in groups defined by dietary micronutrient intake. This study suggests no effect of dietary micronutrients in relation to overall mortality. Supplemental folic acid was found to be associated with increased mortality, but further studies are required. No other supplemental micronutrient was associated with mortality.Food & Nutrition Research 01/2012; 56.
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ABSTRACT: Objective To explore if there is an increased cancer risk associated with folic acid supplements given orally. Design Systematic review and meta-analysis of controlled studies of folic acid supplementation in humans reporting cancer incidence and/or cancer mortality. Studies on folic acid fortification of foods were not included. Data sources Cochrane Library, Medline, Embase and Centre of Reviews and Dissemination, clinical trial registries and hand-searching of key journals. Results From 4104 potential references, 19 studies contributed data to our meta-analyses, including 12 randomised controlled trials (RCTs). Meta-analysis of the 10 RCTs reporting overall cancer incidence (N=38 233) gave an RR of developing cancer in patients randomised to folic acid supplements of 1.07 (95% CI 1.00 to 1.14) compared to controls. Overall cancer incidence was not reported in the seven observational studies. Meta-analyses of six RCTs reporting prostate cancer incidence showed an RR of prostate cancer of 1.24 (95% CI 1.03 to 1.49) for the men receiving folic acid compared to controls. No significant difference in cancer incidence was shown between groups receiving folic acid and placebo/control group, for any other cancer type. Total cancer mortality was reported in six RCTs, and a meta-analysis of these did not show any significant difference in cancer mortality in folic acid supplemented groups compared to controls (RR 1.09, 95% CI 0.90 to 1.30). None of the observational studies addressed mortality. Conclusions A meta-analysis of 10 RCTs showed a borderline significant increase in frequency of overall cancer in the folic acid group compared to controls. Overall cancer incidence was not reported in the seven observational studies. Prostate cancer was the only cancer type found to be increased after folic acid supplementation (meta-analyses of six RCTs). Prospective studies of cancer development in populations where food is fortified with folic acid could indicate whether fortification similar to supplementation moderately increases prostate cancer risk.BMJ Open 01/2012; 2(1):e000653. · 1.58 Impact Factor
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ABSTRACT: PURPOSE: B vitamins and methionine have been postulated to have potential effects on carcinogenesis; however, findings from previous epidemiologic studies on B vitamins, methionine, and lung cancer risk are inconsistent. We investigated associations of dietary intakes of B vitamins (i.e., riboflavin, niacin, vitamin B6, folate, and vitamin B12) and methionine with lung cancer risk among female never smokers. METHODS: The Shanghai Women's Health Study, a population-based, prospective cohort study, included 74,941 women. During a median follow-up of 11.2 years, 428 incident lung cancer cases accrued among 71,267 women with no history of smoking or cancer at baseline. Baseline dietary intakes were derived from a validated, interviewer-administered food frequency questionnaire. Cancer incidence and vital status were ascertained through annual linkage to the Shanghai Cancer Registry and Shanghai Vital Statistics Registry databases and through biennial in-person follow-ups with participants. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox regression. RESULTS: Dietary riboflavin intake was inversely associated with lung cancer risk (HR = 0.62; 95 % CI = 0.43-0.89; p trend = 0.03 for the highest quartile compared with the lowest). A higher than median intake of methionine was associated with lower risk of lung cancer (HR = 0.78; 95 % CI = 0.60-0.99); however, there was no dose-response relation. Intakes of other B vitamins were not associated with lung cancer risk. CONCLUSIONS: Our study suggests that dietary riboflavin intake may be inversely associated with lung cancer risk among female never smokers, which warrants further investigation.Cancer Causes and Control 10/2012; · 3.20 Impact Factor