Dietary intake of nutrients involved in folate-mediated one-carbon metabolism and risk for endometrial cancer

Int J Epidemiol. 2019 Apr 1;48(2):474-488. doi: 10.1093/ije/dyy270.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Carbon / metabolism*
  • Case-Control Studies
  • Diet*
  • Endometrial Neoplasms / epidemiology*
  • Endometrial Neoplasms / metabolism
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Methionine / administration & dosage*
  • Middle Aged
  • Obesity / epidemiology
  • Overweight / epidemiology
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Vitamin B Complex / administration & dosage*


  • Vitamin B Complex
  • Carbon
  • Folic Acid
  • Methionine