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

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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / classification
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carbon / metabolism*
  • Eating
  • Energy Intake*
  • Female
  • Follow-Up Studies
  • Humans
  • Micronutrients*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Risk Factors
  • Surveys and Questionnaires

Substances

  • Micronutrients
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Carbon
  • ERBB2 protein, human
  • Receptor, ErbB-2

Grants and funding

This study was funded by the Italian Ministry of Public Health. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.