Abstract 819: Consumption of fruits, vegetables and fiber and risk of colorectal cancer: A gene environment interaction analysis
Authors: Papadimitriou Nikos , Hidaka Akihisa , Kim Andre , Dimou Niki , Murphy Neil , Berndt Sonja I. , Conti David , Campbell Peter T. , Casey Graham , Figueiredo Jane C. , Tsilidis Konstantinos K. , Gruber Stephen B. , Harlid Sophia , Lin Yi , Moreno Victor , Sakoda Lori C. , Obrero Virginia D. , Hsu Li , Gauderman William J. , Gunter Marc , Peters Ulrike 
Published: July 2021

Abstract
Introduction: Consumption of fruits, vegetables and fiber has been associated with lower colorectal cancer (CRC) risk however, it is unclear if genetic variants can modify these associations.
Methods: Within three genetic CRC consortia including up to 76,157 participants (32,859 cases and 43,298 controls) of European descent: the Colorectal Cancer Family Registry (CCFR), the Colorectal Cancer Transdisciplinary (CORECT) Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), one-step [logistic regression case-control analysis and joint two- and three-degrees of freedom (DF) tests] and two-step methods were implemented to identify novel and biologically plausible gene-environment interactions.
Results: Fruits, vegetables and fiber consumption were inversely associated with CRC with odds ratios per quartile increase of 0.89 [95% confidence interval (CI): 0.86, 0.92], 0.91 (95% CI: 0.88, 0.94) and 0.86 (95% CI: 0.84, 0.89) respectively. The logistic regression analysis identified significant interaction effects between rs142981275 adjacent to the ACOT1 gene and fruits consumption (pval:1.91E-8) and the 2DF test, which jointly considers G and GxE effects, also identified this SNP. The 3DF test also considers G and GxE information and further revealed four loci associated with CRC risk, in the genes NEGR1(rs1620977), ZRANB3 (rs1561277), MCM6 (rs4988235), R3HDM1(rs12465802) (all pval:&lt;5E-8) out of which rs1620977 and rs12465802 were the leading independent variants. For vegetables, the 3DF test identified significant interaction effects in the DCBLD1 gene (rs4946259; pval:1.44E-8). Finally, no significant interactions were observed for any genetic variant and fiber consumption. The 2-step approach did not identify additional interactions either.
Conclusion: This study identified statistically significant interactions between several genetic variants and the consumption of fruits and vegetables with CRC risk. Further research is needed to elucidate the exact mechanisms through which these interactions might influence CRC risk.
Citation Format: Nikos Papadimitriou, Akihisa Hidaka, Andre Kim, Niki Dimou, Neil Murphy, Sonja I. Berndt, David Conti, Peter T. Campbell, Graham Casey, Jane C. Figueiredo, Konstantinos K. Tsilidis, Stephen B. Gruber, Sophia Harlid, Yi Lin, Victor Moreno, Lori C. Sakoda, Virginia D. Obrero, Li Hsu, William J. Gauderman, Marc Gunter, Ulrike Peters. Consumption of fruits, vegetables and fiber and risk of colorectal cancer: A gene environment interaction analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 819.