LAUSR

The inclusion of moderate-penetrance cancer susceptibility genes in multigene panel testing poses challenges regarding the optimal management of individuals found to have pathogenic variants in these genes. A recently published counseling framework has provided evidence-based guidance for moderate-penetrance breast and ovarian cancer genes.1 However, no such framework exists for moderate-penetrance colorectal cancer (CRC) susceptibility genes, including CHEK2, APC*I1307K, and monoallelic MUTYH, which are among the most common multigene panel testing findings.2 Currently the only recommendations to address this risk are from the National Comprehensive Cancer Network, which recommends that individuals who carry pathogenic CHEK2 or APC*I1307K variants irrespective of family history, or monoallelic MUTYH with a family history of CRC, undergo earlier and more frequent CRC screening, similar to individuals with a first-degree relative with CRC.3 Whether early and increased CRC screening is truly justified for such carriers in the absence of a family history of CRC is unknown. To better elucidate the appropriate timing of colonoscopy initiation, we calculated the cumulative lifetime risk (CLTR) of CRC as a multiple of the US Surveillance, Epidemiology, and End Results Program (SEER) estimates of ever developing CRC and the observed risk for selected genetic variants (CHEK2 1100delC, CHEK2 I157K, APC*I1307K, monoallelic MUTYH). Population age-specific incidence rates for CRCs were obtained from the 2010–2014 SEER cancer statistics for all races.4 Average relative-risk multipliers were derived from a systematic meta-analysis.5 We estimated 5-year and CLTR using previously described methods and applied the estimated odds ratio (OR) for each genetic variant to population agespecific incidence data.6