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Polygenic Risk Score is a Predictor of Adenomatous Polyps at Screening Colonoscopy [post]

Michael Northcutt, Zhuqing Shi, Michael Zijlstra, Ayush Shah, Siqun Zheng, Eugene Yen, Omar Khan, Mohammad Imran Beig, Polina Imas, Adam Vanderloo, Obaid Ansari, Jianfeng Xu (+1 others)
2020 unpublished
Background: SNP-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy. Methods: We randomly selected 1,769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC
more » ... wenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of <0.5, 0.5-1.5, and >1.5 were categorized as low, average and elevated risk.Results: Among 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p<0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p<0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend <0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p<0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps.Conclusions: GRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.
doi:10.21203/rs.3.rs-62371/v1 fatcat:5xq37zptlnh6nhymm4cw7lm7ge