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PLoS One. 2015 Sep 16;10(9):e0138318. doi: 10.1371/journal.pone.0138318. eCollection 2015.

Micronutrients Involved in One-Carbon Metabolism and Risk of Breast Cancer Subtypes.

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Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Medical Sciences, University of Torino and Human Genetics Foundation (HuGeF), Turin, Italy.
Department of Preventive and Predictive Medicine, Environmental Epidemiology Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy.
Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Ontario, Canada.



Vitamins involved in one-carbon metabolism are hypothesized to influence breast cancer (BC) risk. However, epidemiologic studies that examined associations between B vitamin intake and BC risk have provided inconsistent results. We prospectively examined, in the Italian ORDET cohort, whether B vitamin consumption was associated with risk of BC and BC subtypes.


After a mean follow-up of 16.5 years, 391 BCs were diagnosed among 10,786 cohort women. B vitamin intakes were estimated from food frequency questionnaires. Cox proportional hazard models adjusted for energy intake and confounders, estimated hazard ratios (HR) with 95% confidence intervals (CIs) for BC according to intake.


RRs were 0.61 (95% CI 0.38-0.97 highest vs. lowest quartile; P trend 0.025) for thiamine; 0.48 (95% CI 0.32-0.71; P trend <0.001) for riboflavin; 0.59 (95% CI 0.39-0.90; P trend 0.008) for vitamin B6, and 0.65 (95% CI 0.44-0.95; P trend 0.021) for folate. As regards risk of BC subtypes, high riboflavin and folate were significantly associated with lower risk of estrogen receptor positive (ER+) and progesterone receptor positive (PR+) cancers, and high thiamine was associated with lower risk of ER-PR- cancers. High riboflavin was associated with lower risk of both HER2+ and HER2- cancers, high folate with lower risk of HER2- disease, and high thiamine with HER2+ disease.


These findings support protective effects of thiamine and one-carbon metabolism vitamins (folate, riboflavin, and vitamin B6) against BC in general; while folate may also protect against ER+PR+ and HER2- disease; and thiamine against ER-PR-, and HER2+ disease.

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