(P13-020-25) Associations of Dietary Choline and Betaine With Colorectal Cancer Incidence in the NIH-AARP Diet and Health Cohort

Objectives: Diet and lifestyle are known risk factors for colorectal cancer (CRC), the second overall leading cause of cancer death in the US. Choline and betaine are essential nutrients associated with both colorectal cancer risk and potential prevention. We investigated the associations of their intake with CRC incidence in 485,651 NIH-AARP Diet and Health study participants.

Methods: We included participants aged 50 to 71, followed for an average of 19 years to assess CRC incidence. Cho, Bet, and subtypes (free choline [FC], phosphocholine [PCho], phosphatidylcholine [PC], glycerophosphocholine [GPC], and sphingomyelin [SM]) were calculated using the 124-item NIH Diet History Questionnaire and nutrient density-adjusted for total energy. We calculated sex-specific quintiles and used multivariate Cox proportional hazard regression to estimate associations of Cho and Bet with CRC incidence overall and by anatomic subsite. We stratified the models by sex, race, body mass index categories (BMI), smoking status, and alcohol intake.

Results: Compared to individuals in the lowest quintile of total choline (TChol) intake, those in the highest quintile had a slightly higher CRC risk (HR=1.05; 95%CI=0.99-1.11; P-trend=0.03), while Bet associations were closer to null. Among Chol subtypes, those in the highest quintile of PC were positively associated with CRC risk (HR=1.05; 95%CI=0.99-1.11; P-trend=0.03); whereas GPC and PCho were inversely associated with CRC risk (HR=0.88; 95 CI=0.83-0.93; HR=0.81; 95% CI= 0.77-0.86; P-trend < 0.001 for both). Higher TChol intake was more strongly, positively associated with higher risk for rectal cancer (HR= 1.20; 95% CI=1.08-1.34; P-het < 0.001) than colon cancer. The associations of FC were stronger among Black individuals (HR=0.78; 95% CI=0.56-1.08; P-int=0.04) and those in the normal weight category (HR=1.11; 95% CI=1.01-1.23; P-int=0.01).

Conclusions: Our study suggests that choline is associated with a higher risk of CRC, whereas betaine associations were closer to null. These associations were strongest for rectal cancers. These results should be further studied in diverse populations in combination with biological markers.

Funding Sources: The NIH-AARP Diet and Health study was funded an Intramural Research Program of the NIH- NCI.