Plasma B Vitamins, Alcohol Intake And Breast Cancer Risk Overall And By Hormone Receptor Status: Report From The EPIC Cohort

Marco MATEJCIC, IARC, France
HUYBRECHTS I. 1 , DE BATLLE J. 1 , RICCIC@VISITORS.IARC.FR C. 1 , PERRIER F. 1 , ROMIEU I. 1 , CHAJ»S V. 1

1 Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France

Purpose. As important factors required for the generation of methyl groups, B vitamins may play a role in breast carcinogenesis (BC) through epigenetic changes. However, results from epidemiological studies have been inconsistent. A large nested case-control study within the EPIC study was conducted to evaluate the association between plasma concentrations of folate and vitamin B12 and BC.
 
Methods. A total of 2,491 BC cases were matched to 2,521 controls for study center, age, menopausal status, exogenous hormone use, time of the day at blood donation, fasting status, and phase of the menstrual cycle. Microbiological assays were used to determine plasma concentrations of folate and vitamin B12. Multivariable conditional logistic regression models were used to estimate odds ratios by quartiles of plasma B vitamins. Subgroup analyses were performed by menopausal status, hormone receptor status of breast tumors (ER, PR, and HER2), and levels of alcohol intake. The interaction between plasma folate and vitamin B12 on BC risk was also evaluated.
 
Results. No significant association emerged between plasma B vitamins and BC risk overall and by hormone receptor status. Stratification by menopausal status and alcohol intake unveiled a borderline increased risk associated with increasing levels of plasma vitamin B12 in women consuming high levels of alcohol (ORQ4-Q1=1.30; 95% CI=1.03-1.64; p for trend=0.051), but not in those drinking low amounts of alcohol (ORQ4-Q1=1.00; 95%CI=0.80-1.26; p-trend=0.928) (p-heterogeneity=0.14). Increased risk of BC was associated with increasing levels of plasma vitamin B12 in women with high concentrations of plasma folate (ORQ4-Q1=1.26; 95%CI=1.00–1.60; P-trend=0.014), while no association appeared in women with high levels of plasma folate (ORQ4-Q1=1.03; 95%CI=0.82–1.29; P-trend=0.806) (p-heterogeneity=0.059).
 
Conclusions. High levels of plasma vitamin B12, as biomarker of dietary intake, may increase the risk of BC in women with either high levels of alcohol intake or low levels of dietary/plasma folate.