Abstract

Abstract Colorectal cancer (CRC) incidence has been declining in the U.S. overall; however, the incidence of CRC in individuals less than 50 years of age (early-onset disease) has been increasing over the last several decades in the U.S. and elsewhere. Furthermore, cancers diagnosed in people less than 50 years of age tend to be characterized by advanced stage and greater propensity for recurrence, increasing the urgency of this emerging public health problem. Responding to the rapid rise in early-onset CRC, some CRC screening guidelines have changed to lower the screening age from 50 to 45, for average risk individuals. Our purpose was to identify genetic, environmental and lifestyle risk factors for early-onset CRC which could be used in predictive modelling to identify the younger individuals who would most benefit from screening. This research, which included more than 3,500 early-onset CRC and 3,500 comparison controls, serves to comprehensively assess genetic, environmental and lifestyle risks in early-onset CRC, as well as to develop a risk prediction tool specifically for this age group. We found that a polygenic risk score is associated with early-onset CRC, particularly for those without a family history of CRC. Several known CRC environmental and lifestyle risk factors are also linked with early-onset disease. In summary, the absolute risk for CRC in young people is low; however, genetic, environmental and lifestyle information provides initial stratification into low and high-risk groups. These findings may contribute to the identification of individuals susceptible to early-onset CRC for tailored early detection or other preventive interventions. Citation Format: Richard B. Hayes. Risk factors for early-onset colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA012.

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