Abstract 1904: B vitamin intake and incidence of colorectal cancer by tumor site and stage: Results from the Women's Health Initiative cohort

Introduction: The role of one-carbon metabolism related nutrients (folate, riboflavin (B2), B6, and B12) in colorectal carcinogenesis is still not fully understood. Folate and other B vitamins are essential for DNA methylation and repair and higher levels have been associated with a decreased risk for colorectal cancer (CRC) in some studies; however, non-linear relationships have been observed. We investigated the dietary intake of one-carbon nutrients and CRC risk in the WHI Observational Study, a large cohort of postmenopausal women. Methods: Dietary intake of folate and other B vitamins was determined via a Food Frequency Questionnaire and supplement inventory in 88,045 healthy women (aged 50 – 79 years, recruited between 1994 – 1998). Multivariate Cox proportional hazards regression models was used to estimate associations between nutrient intake and CRC risk and to evaluate differences in the associations by tumor site and stage. Hazard ratios (HR) for the 4th vs. 1st quartile were estimated. Results: In age-adjusted analyses significantly reduced risks for CRC were observed for the total (supplemental plus dietary) intake of folate (HR=0.82, 95%CI=0.68-0.97), vitamin B12 (HR=0.82, 0.69-0.99), vitamin B6 (HR=0.77, 0.65-0.92), and riboflavin (HR=0.75, 0.63-0.90). After multivariate adjustment (age, BMI, race, prior colonoscopy, smoking, physical activity, postmenopausal HT use) only the total intake of riboflavin (HR=0.80, 0.66-0.96) remained associated with a reduced risk for CRC. For the intake of vitamin B6 a borderline significance was observed (p=0.06, HR=0.85, 0.70-1.02). A site-specific observation was notable for supplemental and total riboflavin intake with a reduced risk for cancer of the distal colon (HRsupp=0.56, 0.33-0.96; HRtotal=0.69, 0.46-1.04) but not in proximal and rectal cancer. In regards to tumor stage, no significant difference was detected for localized and distant disease; the inverse association between the supplemental and total intake of riboflavin and vitamin B6 was limited to regionally spread disease (HRB2;supp=0.66, 0.45-0.96; HRB2;total=0.73, 0.54-0.99; HRB6;supp=0.69, 0.49-0.98; HRB6;total=0.72, 0.53-0.97). Conclusion: Higher riboflavin and vitamin B6 intake was linked to decreased risk for colorectal cancer in a large cohort of postmenopausal women, with some suggestion for stage- and site-specific associations. Our study provides limited support for an association of other B vitamins with CRC risk. (NIH R01 CA120523,