Background: Studies disagree as to whether intakes of folate-mediated one-carbon metabolism nutrients are associated with endometrial cancer.
Methods: Using data from the large, prospective NIH-AARP Diet and Health Study, we used Cox proportional hazards models to evaluate endometrial cancer risk associated with calorie-adjusted dietary intake of several B vitamins and methionine. All models accounted for age, race, body mass index (BMI), smoking, oral-contraceptive use, menopausal hormone therapy use and caloric intake. We estimated associations by time from baseline (≤3 or >3 years) and stratified models by BMI (<25 or ≥25 kg/m2). During 16 years of follow-up, we identified 2329 endometrial cancer cases among 114 414 participants.
Results: After adjustment for confounding, we observed increased risk for endometrial cancer with greater consumption of dietary total folate, natural folate, B2, B6 and B12 [hazard ratios (HRs) ranging from 1.14 to 1.24 for the highest quintile (Q5) vs the lowest (Q1)]. Higher intakes of total folate, natural folate, B6 and B12 continued to be associated with increased risk when limiting follow-up to >3 years from baseline. We observed risks for the highest intakes of B2 [Q5 vs Q1: HR 1.27 95% confidence interval (CI) 1.07-1.50], B12 (Q5 vs Q1: HR 1.38 CI 1.17-1.63) and methionine (Q5 vs Q1: HR 1.26 CI 1.07-1.48) among women who were overweight/obese, but not among normal/underweight women.
Conclusions: Our findings indicate that one-carbon metabolism plays a role in endometrial carcinogenesis and exploration of this role in tissue and cellular biology studies is warranted.
Keywords: diet; endometrial cancer; folate-mediated one-carbon metabolism; prospective cohort study.
Published by Oxford University Press on behalf of the International Epidemiological Association 2018. This work is written by US Government employees and is in the public domain in the US.