Abstract
Purpose:This study investigated the utility of modeling modifiable lifestyle risk factors in addition to genetic variation in colorectal cancer (CRC) screening/prevention.Methods:We derived a polygenic risk score for CRC susceptibility variants in combination with the established nongenetic risk factors of inflammatory bowel disease (IBD), adiposity, alcohol, red meat, fruit, vegetables, smoking, physical activity, and aspirin. We used the 37 known risk variants and 50 and 100% of all risk variants as calculated from a heritability estimate. We derived absolute risk from UK population age structure, incidence, and mortality rate data.Results:Taking into account all risk factors (known variants), 42.2% of 55- to 59-year-old men with CRC have a risk at least as high as that of an average 60-year-old, the minimum eligible age for the UK NHS National Bowel Cancer Screening Program. If the male population is stratified by known variants and IBD status, then risk-difference estimates imply that for 10,000 50-year-old men in the 99th percentile, 760 cases could be prevented over a 25-year period through the modifiable risk factors, but in the lowest percentile, only 90 could be prevented.Conclusion:CRC screening and prevention centered on modifiable risk factors could be optimized if targeted at individuals at higher polygenic risk.Genet Med19 3, 314–321.
Highlights
Colorectal cancer (CRC) is a significant public health issue in developed countries.[1]
If the male population is stratified by known variants and inflammatory bowel disease (IBD) status, risk-difference estimates imply that for 10,000 50-year-old men in the 99th percentile, 760 cases could be prevented over a 25-year period through the modifiable risk factors, but in the lowest percentile, only 90 could be prevented
CRC screening and prevention centered on modifiable risk factors could be optimized if targeted at individuals at higher polygenic risk
Summary
Colorectal cancer (CRC) is a significant public health issue in developed countries.[1] Despite advances in the clinical management of CRC, 5-year patient survival is typically only approximately 55%.2 This poor prognosis and the increasing incidence rates seen in Western countries[1] have provided strong motivation for establishing population screening programs for early detection of CRC.[3,4] there is increasing interest in developing and implementing strategies to lessen the risk of developing CRC. The effectiveness of screening and prevention programs is likely to be optimized if directed toward those identified to be at highest risk for CRC. To date, methods for predicting the individuals in the population who are at increased risk and in whom targeted prevention can be directed have been relatively limited
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