Prediagnostic Plasma Pyridoxal 5 '-Phosphate (Vitamin B6) Levels and Invasive Breast Carcinoma Risk: The Multiethnic Cohort
ABSTRACT BACKGROUND: Evidence from experimental and epidemiologic studies suggests that vitamin B6 may reduce the risk of breast cancer.METHODS: We examined the association of prediagnostic plasma concentrations of pyridoxal-5'-phosphate (PLP), an active form of vitamin B6, with postmenopausal breast cancer risk in a case-control study nested in the multiethnic cohort in Hawaii and Southern California, including 706 cases and 706 controls matched on date of birth, ethnicity, study site, date of blood draw, time of blood draw, hours of fasting before blood draw, and use of menopausal hormones. OR and 95% confidence intervals (CI) were calculated using conditional logistic regression models.RESULTS: Women with plasma PLP concentrations in the highest quartile had a 30% reduced risk of invasive breast cancer (CI: 0.50-0.98) as compared with the women in the lowest PLP quartile (P for trend = 0.02). The association seemed to be limited in cases with hormone receptor-positive tumors (P for heterogeneity = 0.04); and remained unchanged in the analysis restricted to women with blood samples collected more than one year before cancer diagnosis (OR = 0.69; CI: 0.48-0.99; P for trend = 0.03).CONCLUSIONS: These data suggest that higher circulating levels of vitamin B6 are associated with a reduced risk of invasive postmenopausal breast cancer.Impact: These results, in combination with information from two other prospective studies, suggest a role for vitamin B6 in the prevention of postmenopausal breast cancer. Additional studies are needed to further investigate potential heterogeneity of the vitamin B6 association with breast cancer risk by tumor hormone receptor status. Cancer Epidemiol Biomarkers Prev; 1-7. ©2012 AACR.
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ABSTRACT: Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4vs.Q1] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, P for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4vs.Q1 0.63, 95% CI 0.35-1.16, P for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (P for trend 8x10(-4) ), as well as for oropharynx cancer (P for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck. © 2014 Wiley Periodicals, Inc.
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ABSTRACT: Background: Rats fed diets deficient in choline develop hepatocellular carcinoma (HCC). Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and HCC risk have been lacking. Methods: We prospectively examined the association between prediagnostic serum concentrations of one-carbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing HCC based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for established risk factors for HCC. Results: Serum choline and PLP were associated with statistically significant reduced risk of HCC, while serum cystathionine, methionine and SAM were associated with increased HCC risk (all Ptrend<0.05). The inverse associations for HCC risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16, 0.78) (P=0.010) and 0.44 (0.25, 0.78) (P=0.005), respectively. There were no associations for HCC risk with 5-MTHF, betaine, or homocysteine. Conclusion: The inverse associations between choline and vitamin B6 and the risk of HCC development are novel and warrant further investigation. Impact: Identifying new modifiable factors for HCC prevention are warranted.Cancer Epidemiology Biomarkers & Prevention 07/2013; 22(10). DOI:10.1158/1055-9965.EPI-13-0497 · 4.32 Impact Factor
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ABSTRACT: 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.British Journal of Cancer advance online publication, 1 August 2013; doi:10.1038/bjc.2013.438 www.bjcancer.com.British Journal of Cancer 08/2013; 109(7). DOI:10.1038/bjc.2013.438 · 4.82 Impact Factor