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Abstract
The aim of this study was to compare and externally test the performance of risk scores developed to predict new cases of colorectal cancer that include common genetic variants (SNPs), with or without established lifestyle/environmental (questionnaire-based/classical/phenotypic) risk factors. Adding phenotypic risk factors without age improved the ability of models to predict colorectal cancer risk in men but not in women. Adding phenotypic risk factors and age improved risk score performance in all cases, with the best performing models including SNPs, phenotypic risk factors, and age. Among middle-aged people in the UK, existing risk scores including SNPs discriminate moderately well between those who do and do not develop colorectal cancer over 6 years. Consideration should be given to exploring the feasibility of incorporating genetic and lifestyle/environmental information in any future stratified colorectal cancer screening program.