Introduction: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, it is unclear whether the reduction in CRC risk may differ by genetic susceptibility. Methods: We evaluated this question in a cohort of 304,740 participants of European descent aged ≥ 50 years. Genetic susceptibility was measured using a polygenic risk score (PRS) constructed with risk variants identified in genome-wide association studies. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of CRC risk. Results: Over a median follow-up of 7.0 years, 2,261 incident CRC cases and 528 CRC deaths were identified. CRC screening was associated with a significantly reduced CRC incidence among individuals with a high (HR, 0.80; 95% CI, 0.71-0.92) and intermediate PRS (0.84, 0.71-0.98) but not among those with a low PRS (1.03, 0.86-1.25; Pinteraction, 0.005). A similar but more evident difference was observed for mortality (Pinteraction, 0.046), with more than 30% reduced mortality observed in the high PRS group (0.69, 0.52- 0.91). Among the younger group (age 50-60 years), CRC screenings were associated with a slightly (but non-significantly) elevated incidence and mortality in the low PRS group but a reduced risk in the high PRS group (Pinteraction, 0.043 [incidence]; 0.092 [mortality]). No significant interaction was observed in the older group (age > 60 years). Conclusion: Individuals with a higher genetic risk benefited more substantially from CRC screenings than those with a lower risk. Our findings suggest that PRS may be used to develop personalized CRC screening to maximize its effect on CRC prevention.
Dr. Jungyoon Choi (MD, PhD: Korea University) is currently working as a clinical assistant professor at Korea University Hospital. Her doctoral thesis investigated the genomic profiles of colorectal cancer. From 2019-2021, she joined Dr. Wei Zheng's laboratory as a postdoctoral fellow at the Vanderbilt University Medical Center, where her research encompassed big data, bioinformatics, cancer genetics/genomics, and cancer epidemiology. Her research interests include the use of bioinformatics to understand the epidemiology and etiology of cancer, with a focus on the role of genetics and genomics to identify prognostic and predictive biomarkers. A medical oncologist, Dr. Choi also has clinical experience in treating patients with various types of cancer (especially colorectal, stomach, esophageal, hepatobiliary, and pancreatic cancers). She is eager to bridge the gap between genome research and clinical practice.
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