Abstract 6449: Association between dietary one-carbon metabolism-related nutrients and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study
Authors: Pham Yen Thi-Hai , Jin Aizhen , Wang Renwei , Koh Woon-Puay , Yuan Jian-Min , Luu Hung N. 
Published: June 2023

Abstract
Background. Colorectal cancer (CRC) is a commonly diagnosed subtype of cancer with a high mortality rate. One-carbon metabolism is a set of complex pathways, responsible for providing methyl group for DNA synthesis, repair and methylation. Adequate DNA methylation maintains chromosome stability and prevents gene disruption. Diet is a major source for key substrates and co-factors (i.e., vitamin B6, choline and folate) involved in one-carbon metabolism. A majority of epidemiologic studies that have evaluated one-carbon metabolism-related nutrients in relation to CRC risk have focused on the potential role of folate only. Due to the involvement of multiple nutrients and the complexity of one-carbon metabolism pathways, a comprehensive assessment of the nutrients involved and their associations with CRC risk is needed. The purpose of the current analysis was therefore to evaluate the association between one-carbon metabolism-related nutrients with the risk of developing CRC using the Singapore Chinese Health Study (SCHS).
Methods. The SCHS is an on-going population-based prospective cohort study that includes 61,321 Chinese men and women in Singapore who were 45-74 years of age at baseline. A 165-item semi-quantitative food frequency questionnaire was used to obtain information of dietary intake. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) and respective 95% confidence intervals (CIs) for CRC associated with one-carbon metabolism-related nutrients, including thiamine, riboflavin, niacin, vitamin B6, folate acid, vitamin B12, choline, methionine, and betaine, adjusting for potential confounders.
Results. After an average of 17.5 years of follow-up, 2,140 participants developed CRC. An inverse association between folate acid and colon cancer. The HRs and respective 95% CIs for quarters 2, 3 and 4 vs. quarter 1 (the lowest quartile) was 0.98 (0.84-1.14), 0.93 (0.79-1.10) and 0.80 (0.64-0.98) (Ptrend=0.04). Similar pattern was observed between folate acid intake and colon cancer risk among never smokers (HRQ4vsQ1=0.67, 95% CI: 0.51-0.86; Ptrend=0.005). No association was found between other one-carbon metabolism-related nutrients and the risk of colorectal cancer
Conclusions. In a large on-going prospective cohort study of more than 61,000 Chinese Singaporeans, we found inverse associations between dietary folate acid and the risk of colon cancer. This association was more obvious among never smokers. Our findings provide critical implication for primary prevention and control of colorectal cancer.
Citation Format: Yen Thi-Hai Pham, Aizhen Jin, Renwei Wang, Woon-Puay Koh, Jian-Min Yuan, Hung N. Luu. Association between dietary one-carbon metabolism-related nutrients and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6449.