Abstract 2355: Folate and Folic Acid Intake in Relation to Molecular Subtypes of Colorectal Cancer; a Pooled Analysis of 7542 Cases

Abstract Background: Higher folate intake has been reported to be associated with modestly lower risk of colorectal cancer, but the overall state of the evidence is inconclusive. Revisiting putative and established lifestyle-related risk factors from the perspective of intertumoral heterogeneity is warranted, as risk relationships for a molecular subtype may be attenuated toward the null when colorectal cancer is investigated as a single disease. Aim: To investigate folate and folic acid intakes in relation to the risk of molecular subtypes of colorectal cancer. Methods: We pooled individual-level observational data from 7542 colorectal cancer cases and 7066 controls within the collaborative framework of the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR). Odds ratios per sex- and study-specific quartile increase in dietary and total folate intake, and for folic acid supplement use (yes/no), were estimated using logistic regression for case-only analyses and multinomial models for case-control analyses. Minimally adjusted analyses included sex, age, study and total energy intake as covariates. Tumor marker variables included microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations. Results: In case-only analyses, we observed no heterogeneity in associations between folate intake, with or without supplemental folic acid (taking into consideration folic acid fortification when relevant), or with folic acid supplement use, and the risk of any subtype of colorectal cancer based on individual molecular tumor markers (lowest p for heterogeneity 0.073). In case-control analyses, higher dietary and total folate intake and folic acid supplement use were associated with a lower risk of most molecular tumor subtypes (all odds ratios were below one, and most were statistically significant). Adjustment for a larger set of potential confounders had no material effect on risk estimates. Conclusion: In this large, pooled analysis, higher dietary and total folate intakes and folic acid supplement use were all associated with a lower risk of colorectal cancer, regardless of individual molecular tumor markers including MSI status, CIMP, and BRAF and KRAS mutations. Citation Format: Bethany Van Guelpen, Björn Gylling, Sophia Harlid, Anna Winkvist, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Steven J. Gallinger, Graham G. Giles, Marc J. Gunter, Michael Hoffmeister, Li Hsu, Mark A. Jenkins, Roger L. Milne, Polly A. Newcomb, Shuji Ogino, John D. Potter, Conghui Qu, Lori C. Sakoda, Robert E. Schoen, Martha L. Slattery, Mikael O. Woods, Tabitha A. Harrison, Ulrike Peters. Folate and folic acid intake in relation to molecular subtypes of colorectal cancer; a pooled analysis of 7542 cases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2355.