Dietary B vitamin and methionine intakes and lung cancer risk among female never smokers in China

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.     

Dietary consumption of antioxidant vitamins and subsequent lung cancer risk: The Japan Public Health Center‐based prospective study

While many epidemiological studies have studied the association between lung cancer risk and fruits and vegetable consumption (the major sources of antioxidant vitamins), only a few have investigated the direct association with antioxidants in consideration of cancer subtypes and smoking status. Here, we examined the association between consumption of antioxidant vitamins and lung cancer risk in one of the largest prospective cohort studies in Japan. We investigated the association of dietary antioxidant vitamins intake, namely retinol, vitamin C, vitamin E, α‐carotene, and β‐carotene and subsequent incidence of lung cancer among 38,207 men and 41,498 women in the Japan Public Health Center‐based prospective study. Cox proportional hazard regression was performed with adjustment for potential confounders and by strata of cancer subtypes and smoking status. Antioxidant and other dietary intakes were assessed using a food frequency questionnaire (FFQ). During 1,233,096 person‐years of follow‐up between 1995 and 2013, a total of 1,690 lung cancer cases were newly diagnosed. In a multivariate regression model, while higher retinol intake was positively associated with overall lung cancer risk in men (HR 1.26; 95% CI 1.05–1.51; p_trend = 0.003), the estimates were more evident with small cell carcinoma (HR 1.92; 95% CI 1.13–3.24; p_trend < 0.001). Null associations were observed for other antioxidant vitamins. Our prospective study suggests that higher consumption of retinol may be associated with an increased risk of lung cancer in men, especially with small cell carcinoma, although confirmation is required.     

Vitamin E intake and the lung cancer risk among female nonsmokers: A report from the Shanghai Women's Health Study

Vitamin E includes several tocopherol isoforms, which may reduce lung cancer risk, but past studies evaluating the association between vitamin E intake and lung cancer risk were inconsistent. We prospectively investigated the associations between tocopherol intake from diet and from supplements with lung cancer risk among 72,829 Chinese female nonsmokers aged 40–70 years and participating in the Shanghai Women's Health Study (SWHS). Dietary and supplement tocopherol exposure was assessed by a validated food‐frequency questionnaire at baseline and reassessed for change in intake during follow‐up. Cox proportional hazards models with time‐dependent covariates were used to calculate multivariate‐adjusted hazard ratios (HRs) and 95% confidence interval (CIs) for lung cancer. After 12.02 years of follow‐up, 481 women were diagnosed with lung cancer. Total dietary tocopherol was inversely associated with lung cancer risk among women meeting dietary guidelines for adequate intake (AI) of tocopherol (14 mg/day or more: HR: 0.78; 95% CI 0.60–0.99; compared with the category less than AI). The protective association between dietary tocopherol intake and lung cancer was restricted to women exposed to side‐stream smoke in the home and workplace [HR = 0.53 (0.29–0.97), p‐trend = 0.04]. In contrast, vitamin E supplement use was associated with increased lung cancer risk (HR: 1.33; 95% CI: 1.01–1.73), more so for lung adenocarcinoma risk (HR: 1.79; 95% CI: 1.23–2.60). In summary, dietary tocopherol intake may reduce the risk of lung cancer among female nonsmokers; however, supplements may increase lung adenocarcinoma risk and requires further investigation.     

Micronutrient intake and risk of prostate cancer in a cohort of middle-aged, Danish men

Purpose

Micronutrients may protect against prostate cancer. However, few studies have had high-quality assessment of both dietary and supplemental consumption of micronutrients, rendering possible different source-specific effects difficult to discern. This study evaluates associations between intake of vitamin C, E, folate, and beta-carotene and prostate cancer risk, focusing on possible different effects of dietary, supplemental, or total intake and on potential effect modification by alcohol intake and BMI.

Methods

Danish prospective cohort study of 26,856 men aged 50–64 years with questionnaire-based information on diet, supplements, and lifestyle. Hazard ratios (HRs) for prostate cancer associated with micronutrient intake were calculated using Cox proportional hazard analyses.

Results

During follow-up (1993–2010), 1,571 prostate cancer cases were identified. Supplemental folic acid was inversely associated with prostate cancer risk, notably on a continuous scale [HR 0.88 (95 % CI 0.79–0.98) per 100 μg increase/day]. The risk reduction was largely confined to non-aggressive tumors [HR 0.71 (0.55–0.93) per 100 μg increase/day]. No influence on prostate cancer risk was observed for dietary folate or for the other studied micronutrients, regardless of source. We found no significant effect modification by alcohol intake and BMI in relation to any micronutrient.

Conclusion

Our study may indicate an inverse association between folic acid and prostate cancer; however, the inverse association was confined to supplemental folic acid and non-aggressive prostate cancer and may thus be a chance finding. Further studies are warranted to evaluate our findings.     

Association Between One-carbon Metabolism-related Vitamins and Risk of Breast Cancer: A Systematic Review and Meta-analysis of Prospective Studies

Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B₆, vitamin B₂, vitamin B₁₂) and breast cancer risk have reported inconsistent findings. We conducted a systematic search of the reported data and performed a meta-analysis of prospective case-control and cohort studies to derive a more precise evaluation. The PubMed and EMBASE databases were searched to identify eligible studies. A total of 27 studies involving 49,707 cases and 1,274,060 individuals were included in the meta-analysis. The results indicated that a high intake of folate, vitamin B₆, and vitamin B₂ might decrease the risk of breast cancer. The corresponding pooled relative risks (RRs) for the highest intake compared with the lowest were 0.93 (95% confidence interval [CI], 0.88-0.99; P = .018), 0.94 (95% CI, 0.89-1.00; P = .037) and 0.90 (95% CI, 0.82-0.99; P = .026). No significant association between vitamin B₁₂ and breast cancer risk was found (RR, 0.99; 95% CI, 0.94-1.04; P = .604). Further study showed that folate and vitamin B₆ might decrease the risk of estrogen receptor-negative (ER⁻)/progesterone receptor-negative (PR⁻) breast cancer but not ER⁺/PR⁺ breast cancer. The dose–response meta-analysis indicated a significant linearity relationship between folate intake and a reduced risk of ER⁻/PR⁻ breast cancer. An increment of folate intake (100 μg/d) corresponded to a 7% deceased risk of ER⁻/PR⁻ breast cancer (RR, 0.93; 95% CI, 0.89-0.98; P = .007). In conclusion, a high intake of 1-carbon metabolism-related vitamins might contribute to the prevention of breast cancer, especially ER⁻/PR⁻ breast cancer.     

Vitamin supplement use and risk for breast cancer: the Shanghai Breast Cancer Study

Objective The influence of vitamin supplements on breast cancer risk is unclear and the interactive effects of dietary and supplemental sources are unknown. This study investigated (1) the association between self-reported vitamin supplement use (multivitamin, A, B, C, and E) and breast cancer and (2) the combined effect of vitamin supplements in relation to dietary vitamin intakes on breast cancer risk. Methods The Shanghai Breast Cancer Study was a population-based case-control study conducted in Shanghai in 1996-1998 (Phase I) and 2002-2004 (Phase II). Participants were aged 25-64 (Phase I) and 20-70 years (Phase II). The analyses included 3,454 incident breast cancer cases and 3,474 controls. Unconditional logistic regression models were used to determine adjusted odds ratios (ORs) for breast cancer risk associated with vitamin supplement use. Results Overall, breast cancer risk was not related to any vitamin supplement intake. However, a 20% reduction in breast cancer risk was observed with vitamin E supplement use among women with low-dietary vitamin E intake (OR = 0.8; 95% confidence interval (CI), 0.6-1.0). A non-significant 20% risk reduction was observed among vitamin B supplement users with low B dietary intake (OR = 0.8; 95% CI, 0.6-1.1). Frequent use of a vitamin B supplement was adversely associated with breast cancer risk among those with high dietary vitamin B intake (OR = 1.4; 95% CI: 0.9-2.1; P for interaction = 0.07). Conclusions This study suggests that vitamins E and B supplements may confer protection against breast cancer among women who have low dietary intake of those vitamins.     

One-carbon metabolism-related micronutrients intake and risk for hepatocellular carcinoma: A prospective cohort study

Deficient intake of micronutrients involved in one-carbon metabolism (eg, choline, methionine, vitamin B₁₂ and folic acid) leads to hepatocellular carcinoma (HCC) development in rodents, but is under-investigated in humans. We investigated the association between one-carbon metabolism-related micronutrient intake and HCC risk in a prospective cohort of 494 860 participants with 16 years of follow-up in the NIH-AARP study. Dietary intakes and supplement use were ascertained at baseline using a food-frequency questionnaire. Total intake (diet plus supplements) of the following one-carbon metabolism-related micronutrients were calculated: folate, methionine and vitamins B₂ (riboflavin), B₃ (niacin), B₆ and B₁₂. These micronutrients were examined both individually and simultaneously, with adjustment for covariates. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over the 16-year follow-up period, 647 incident HCC cases were diagnosed. When examined individually, higher total vitamin B₃ intake was associated with a lower HCC risk (HR_{Q5 vs Q1} = 0.60; 95% CI = 0.42-0.85; P_trend = .008), and the association remained significant when all six micronutrients were examined simultaneously (HR_{Q5 vs Q1} = 0.32; 95% CI = 0.18-0.55; P_trend < .0001). Among participants with >3 years of follow-up, higher total vitamin B₃ intake was again associated with lower risk (HR_{Q5 vs Q1} = 0.37; 95% CI = 0.20-0.68; P_trend = .001), whereas higher total vitamin B₆ intake was associated with higher risk (HR_{Q5 vs Q1} = 2.04; 95% CI = 1.02-4.07; P_trend = .04). Restricted cubic spline analyses showed a dose-response inverse association between total vitamin B₃ intake and HCC risk, and dose-response positive association between total vitamin B₆ intake and HCC risk. The study suggests that higher vitamin B₃ intake is associated with lower HCC risk, whereas higher vitamin B₆ intake is associated with increased risk.     

Intake of fatty acids and antioxidants and pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area

There are no well‐established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all p_trend < 0.01), monounsaturated palmitoleic and oleic fatty acids [OR = 1.6 (95% CI: 1.2–2.1) and 1.4 (95% CI: 1.1–1.9); both p_trend < 0.01], and polyunsaturated linolenic acid [OR = 1.5 (95% CI: 1.1–2.0); p_trend = 0.02]. Inverse associations were observed for high levels of gadolic acid [4th vs. 1st quartile: OR = 0.68 (95% CI: 0.50–0.92); p_trend = 0.007] and omega‐3 fatty acids [≥0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25–0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51–0.94); p_trend = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49–0.92); p_trend = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both p_trend < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega‐3 fatty acids, vitamins C and E may reduce the risk.     

Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers

Data are very limited on vitamin D and lung cancer prevention in high‐risk populations. The authors investigated whether estimated vitamin D intake was associated with lung cancer risk and whether effect modification by vitamin A existed among current/former heavy smokers and workers with occupational exposure to asbestos. A case–cohort study selected 749 incident lung cancers and 679 noncases from the Carotene and Retinol Efficacy Trial (CARET), 1988–2005. The active intervention was supplementation of 30 mg β‐carotene + 25,000 IU retinyl palmitate/day. Baseline total intake including both diet (from food frequency questionnaire) and personal supplements (from brand names linked to the labeled potencies) was assessed. Hazard ratios (HRs) were estimated by Cox proportional hazard models. No significant association of total vitamin D intake with lung cancer was observed overall. However, total vitamin D intake ≥600 versus <200 IU/day was associated with a lower risk of non‐small cell lung cancer among former smokers [HR = 0.36, 95% confidence interval (CI) = 0.13–0.96]. Total vitamin D intake ≥400 versus <400 IU/day was associated with a lower risk of total lung cancer among participants who received the CARET active intervention (HR = 0.56, 95% CI = 0.32–0.99) and among those who had total vitamin A intake ≥1,500 µg/day retinol activity equivalent (RAE; HR = 0.46, 95% CI = 0.23–0.91). The beneficial associations were attenuated among those who did not receive the CARET active intervention or who had total vitamin A intake <1,500 µg/day RAE (p‐interaction = 0.02 for current smokers). Our observation suggests that vitamin A may assist vitamin D in preventing lung cancer among smokers.     

Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.     

Markers of vitamin B6 status and metabolism as predictors of incident cancer: The Hordaland Health Study

Dietary intake and/or circulating concentrations of vitamin B6 have been associated with risk of cancer, but results are inconsistent and mechanisms uncertain. Pyridoxal 5'‐phosphate (PLP) is the most commonly used marker of B6 status. We recently proposed the ratio 3‐hydroxykynurenine/xanthurenic acid (HK/XA) as an indicator of functional vitamin B6 status, and the 4‐pyridoxic acid (PA) /(pyridoxal (PL) +PLP) ratio (PAr) as a marker of vitamin B6 catabolism during inflammation. We compared plasma PLP, HK/XA and PAr as predictors of cancer incidence in a prospective community‐based cohort in Norway. This study included 6,539 adults without known cancer at baseline (1998–99) from the Hordaland Health Study (HUSK). HR and 95% CI were calculated for the risk of overall and site‐specific cancers using multivariate Cox proportional hazards regression with adjustment for potential confounders. After a median follow‐up time of 11.9 years, 963 cancer cases (501 men and 462 women) were identified. Multivariate‐adjusted Cox‐regression showed no significant relation of plasma PLP or HK/XA with risk of incident cancer. In contrast, PAr was significantly associated with risk of cancer with HR (95% CI) = 1.31 (1.12–1.52) per two standard deviation (SD) increment (p < 0.01). Further analysis showed that PAr was a particular strong predictor of lung cancer with HR (95% CI) = 2.46 (1.49–4.05) per two SD increment (p < 0.01). The present results indicate that associations of vitamin B6 with cancer may be related to increased catabolism of vitamin B6, in particular for lung cancer where inflammation may be largely involved in carcinogenesis.     

Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study.

A cohort of 11,580 residents of a retirement community initially free from cancer were followed from 1981 to 1989. A total of 1,335 incident cancer cases were diagnosed during the period. Relative risks of cancer were calculated for baseline consumption of vegetables, fruits, beta-carotene, dietary vitamin C, and vitamin supplements. After adjustment for age and smoking, no evidence of a protective effect was found for any of the dietary variables in men. However, an inverse association was observed between vitamin C supplement use and bladder cancer risk. In women, reduced cancer risks of all sites combined and of the colon were noted for combined intake of all vegetables and fruits, fruit intake alone, and dietary vitamin C. Supplemental use of vitamins A and C showed a protective effect on colon cancer risk in women. There was some suggestion that beta-carotene intake and supplemental use of vitamin A, C, and E were associated with reduced risk of lung cancer in women, but none of these results were statistically significant. These inverse associations observed in women seem to warrant further investigation, although there was inconsistency in results between the sexes.     

Intake of Fruits and Vegetables,Carotenoids, Folate,and Vitamins A,C, E and Risk of Bladder Cancer Among Women (United States)

Objective: To examine the relation between fruits and vegetables, carotenoids, folate, and vitamins A, C, E and the risk of bladder cancer in a prospective study of women Methods: A total of 237 incident bladder cancer cases were documented during 20 years of follow-up among 88,796 women enrolled in the Nurses’ Health Study. Dietary intake was assessed by food-frequency questionnaires every two to four years and incident diagnosis of bladder cancer was ascertained every two years. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) for bladder cancer risk, adjusting for age, pack-years of smoking, current smoking, and total caloric intake. Results: Consumption of total fruits and vegetables was not associated with bladder cancer risk (RR = 1.08, 95% CI = 0.70–1.65, for > 5.5 compared to < 2.5 servings per day). Similarly, dietary intakes of carotenoids, folate, and vitamins A, C, E, were not related to bladder cancer risk. No association was observed between supplemental intake of multivitamins, vitamins A, C, E and bladder cancer risk. Conclusions: We did not observe any association for fruit and vegetable consumption or vitamin intake and bladder cancer risk among women.     

Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort

Objective Vitamin E and selenium are promising nutrients for the prevention of prostate cancer, and both are currently being tested in a large randomized trial for prostate cancer. However, results are not expected for at least 6 years. We aimed to investigate the association of vitamin E and selenium supplementation with prostate cancer in the VITamins And Lifestyle (VITAL) study, a cohort study specifically designed to examine supplement use and future cancer risk. Methods In a prospective design, 35,242 men recruited between 2000 and 2002 from western Washington State completed a questionnaire, including detailed questions about vitamin E and selenium supplement intake during the past 10 years from brand-specific multivitamins and single supplements. Using linkage to the western Washington SEER cancer registry, we documented 830 new cases of prostate cancer from baseline through December 2004. Results A 10-year average intake of supplemental vitamin E was not associated with a reduced prostate cancer risk overall [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.65–1.1 for ≥400 IU/day vs. non-use, p for trend 0.36]; however, risk for advanced prostate cancer (regionally invasive or distant metastatic, n = 123) decreased significantly with greater intake of supplemental vitamin E (HR 0.43, 95% CI 0.19–1.0 for 10-year average intake ≥400 IU/day vs. non-use, p for trend 0.03). There was no association between selenium supplementation and prostate cancer risk (HR 0.90, 95% CI 0.62–1.3 for 10-year average intake >50 μg/day vs. non-use, p for trend 0.97). Conclusions In this prospective cohort, long-term supplemental intake of vitamin E and selenium were not associated with prostate cancer risk overall; however, risk of clinically relevant advanced disease was reduced with greater long-term vitamin E supplementation.     

Dietary folate and vitamin B6 are not associated with p53 mutations in esophageal adenocarcinoma

Recent studies have suggested an association between dietary folate, and related B‐vitamins, and risk for cancer, potentially mediated by the p53 tumor suppressor gene. The aim of this study was to explore the effect of dietary folate and vitamin B₆ intake on p53 in the molecular pathogenesis of esophageal adenocarcinoma (EADC). For each participant, a structured questionnaire was used to obtain detailed sociodemographic and lifestyle risk factors, including diet, from which folate and vitamin B₆ intake were calculated. Risks for p53 mutations, p53 mutations at CpG sites, and p53 protein overexpression among EADC cases (n = 54) were calculated using logistic regression with dietary folate and vitamin B₆ intake as predictive variables, adjusting for age, gender, smoking, and alcohol consumption. No significant differences were found for patients with EADC who had p53 mutations (n = 21) compared with patients with wild‐type p53 (n = 33) with respect to selected clinicopathologic variables (age, gender, tumor grade, stage, alcohol, or tobacco consumption) and dietary intake of folate or vitamin B₆. No statistically significant associations were seen between dietary folate and vitamin B₆ intake (highest vs. lowest quartiles) and p53 mutations, p53 mutations at CpG sites (n = 12), and p53 protein overexpression (n = 17). We conclude that dietary intake of folate and vitamin B₆ do not appear to have an effect on p53, suggesting alternative molecular mechanisms underlying esophageal adenocarcinogenesis. © 2009 Wiley‐Liss, Inc.     

Intake of vitamins A, C, and E from diet and supplements and breast cancer in postmenopausal women

Objective: The influence of the vitamins A, C, and E on breast cancer development has not been clarified. An effect of a vitamin per se implicates similar patterns for the effects of the vitamin from dietary and supplemental sources. We examined how the breast cancer incidence rate among postmenopausal women was related to intake of vitamins A, C, and E from diet and supplements. Methods: Data was sampled as case–control nested within the Danish Diet, Cancer and Health cohort. Data on vitamin intakes were collected at entry into the cohort by means of self-administered questionnaires. Women eligible for the nested case–control study were postmenopausal at entry into the cohort. The analyses were based on 418 cases of incident breast cancer and 394 controls (including two cases). Results: Breast cancer was not significantly related to the intakes of vitamin A or E, whereas a monotonic dose–response relation was seen for the intake of vitamin C. The estimated rate ratio per 100 mg vitamin C was: 2.06 (95% CI: 1.45–2.91) for dietary intake and 1.06 (95% CI: 1.01–1.13) for supplemental intake. Conclusions: We found no evidence of an association between breast cancer and intake of vitamin A or E for postmenopausal women. For vitamin C we found an increase in breast cancer rate with increasing intake.     

Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women

Objective Adequate folate intake may be important for breast cancer prevention. Its protective effect may be influenced by factors associated with folate metabolism. We sought to evaluate folate intake in relation to breast cancer risk and examine whether the relation is affected by alcohol and intake of vitamin B₂ and B₁₂. Methods A prospective cohort analysis of folate intake was conducted among 62,739 postmenopausal women in the French E3N cohort who had completed a validated food frequency questionnaire in 1993. During nine years’ follow-up, 1,812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized in quintiles and energy-adjusted using the regression-residual method. Cox model-derived relative risks (RRs) were adjusted for known breast cancer determinants. Results The multivariate RR for extreme quintiles of folate intake was 0.78 (95% CI: 0.67–0.90; p-trend = 0.001) [Median intake for Q₁ = 296 μg/day and Q₅ = 522 μg/day]. There was no evidence to support effect modification by alcohol or B₂ intake. The decreasing trend was most marked in women with higher folate and vitamin B₁₂ intake. However, test for interaction was not statistically significant (p = 0.29). Conclusions High folate intake was associated with decreased breast cancer risk. Vitamin B₁₂ intake may modify this association.     

Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies

Objective

To evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer.

Methods

Using the primary data from 13 cohort studies, we estimated study- and sex-specific relative risks (RR) with Cox proportional hazards models and subsequently pooled RRs using a random effects model.

Results

Among 676,141 men and women, 5,454 colon cancer cases were identified (7–20 years of follow-up across studies). Vitamin A, C, and E intakes from food only were not associated with colon cancer risk. For intakes from food and supplements (total), the pooled multivariate RRs (95% CI) were 0.88 (0.76–1.02, >4,000 vs. ≤1,000 μg/day) for vitamin A, 0.81 (0.71–0.92, >600 vs. ≤100 mg/day) for vitamin C, and 0.78 (0.66–0.92, >200 vs. ≤6 mg/day) for vitamin E. Adjustment for total folate intake attenuated these associations, but the inverse associations with vitamins C and E remained significant. Multivitamin use was significantly inversely associated with colon cancer risk (RR = 0.88, 95% CI: 0.81–0.96).

Conclusions

Modest inverse associations with vitamin C and E intakes may be due to high correlations with folate intake, which had a similar inverse association with colon cancer. An inverse association with multivitamin use, a major source of folate and other vitamins, deserves further study.     

Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose–response meta-analysis

Background:

Epidemiological studies evaluating the association of vitamin B₆, vitamin B₁₂ and methionine with breast cancer risk have produced inconsistent results.

Methods:

Pertinent studies were identified by a search in PubMed and Web of Knowledge. Random-effect model was used. Dose–response relationship was assessed by restricted cubic spline.

Results:

The combined relative risk (95% confidence interval) of breast cancer for the highest vs lowest category of serum pyridoxal 5′-phosphate (PLP, active form of vitamin B₆) levels and dietary methionine intake was 0.80 (0.66–0.98, P=0.03) and 0.94 (0.89–0.99, P=0.03), respectively, and the associations of breast cancer with higher serum PLP levels and dietary methionine intake were significant among post-menopausal women, but not among pre-menopausal women. The inverse association between breast cancer risk and dietary vitamin B₆ intake, serum vitamin B₁₂ levels and dietary vitamin B₁₂ intake was not significant overall. Linear dose–response relationship was found, and the risk of breast cancer decreased by 23% (P<0.00) for every 100 pmol ml⁻¹ increment in PLP levels and 4% (P=0.05) for every 1 g per day increment in dietary methionine intake, respectively.

Conclusion:

Serum PLP levels and methionine intake might be inversely associated with breast cancer risk, especially among postmenopausal women, which need to be confirmed.     

One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer

Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.