Michael J Northcutt1, Zhuqing Shi2, Michael Zijlstra3, Ayush Shah3, Siqun Zheng2, Eugene F Yen4, Omar Khan4, Mohammad Imran Beig5, Polina Imas5, Adam Vanderloo5, Obaid Ansari5, Jianfeng Xu2, Jay L Goldstein4,6. 1. Division of Gastroenterology, University of Chicago Medicine, NorthShore University HealthSystem, 2650 Ridge Ave, Evanston, IL, 60201, USA. mjnorthcutt@gmail.com. 2. Program for Personalized Cancer Care, NorthShore University HealthSystem, 1001 University Place, 1001 University Place, Evanston, IL, 60201, USA. 3. Department of Internal Medicine, University of Chicago Medicine, NorthShore University HealthSystem, 2650 Ridge Ave, Evanston, IL, 60201, USA. 4. Division of Gastroenterology, University of Chicago Medicine, NorthShore University HealthSystem, 2650 Ridge Ave, Evanston, IL, 60201, USA. 5. Department of Clinical Analytics and Health Information Technology, NorthShore University HealthSystem, 4901 Searle Parkway, Skokie, IL, 60076, USA. 6. , Chicago, IL, 60647, USA.
Abstract
BACKGROUND: Single nucleotide polymorphism (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 1769 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 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.
BACKGROUND: Single nucleotide polymorphism (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 1769 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 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.
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