One‐carbon metabolism‐related nutrients and colorectal cancer risk in the Women's Health Initiative Observational Cohort Study: Are the associations modified by folic‐acid fortification period and alcohol intake?

Abstract

We tested whether one-carbon metabolism-related nutrient intakes were associated with colorectal cancer (CRC) risk and whether folic acid fortification and alcohol use were effect modifiers in postmenopausal women. In the Women's Health Initiative Observational Study, folate and vitamins B12, B6, and riboflavin from food and supplements and alcohol intake were measured by an FFQ and supplement inventory in 88,045 women age 50–79 y during 1994–98. As of 2009, 1,003 incident CRC cases were accrued. Multivariate hazard ratios (HR) for the 4th vs. 1st quartiles of intake were estimated. Reduced CRC risk was associated with high total riboflavin intake in all women (HR=0.80, 95% CI=0.66–0.96) and those enrolled during the peri-fortification period (1996–97; HR=0.71, 0.55–0.91). In women with light alcohol use (<1 drink/wk), total intakes of folate (HR=0.76, 0.56–1.03; p trend<0.05), B12 (HR=0.66, 0.48–0.92), B6 (HR=0.59, 0.43–0.81), and riboflavin (HR=0.64, 0.46–0.88) were associated with reduced CRC risk. These associations were not observed in women with no or heavier (≥1 drink/wk) alcohol use. In conclusion, total riboflavin intake was inversely associated with CRC risk in postmenopausal women, particularly in those enrolled near the beginning of folic acid fortification. Alcohol may modify the associations of total folate, B12, B6, and riboflavin intakes with CRC risk. (NIH R01 CA120523, N01WH22110)