Effects of common genetic variants associated with colorectal cancer risk on survival outcomes after diagnosis: A large population-based cohort study.

Genome-wide association studies have thus far identified 130 genetic variants linked to colorectal cancer (CRC) risk (r  < 0.2). Given their implication in disease causation, and thus plausible biologically effects on cancer-relevant biological pathways, we investigated whether these variants are associated with CRC prognosis and also whether they might provide predictive value for survival outcome. We conducted the analysis in a well-characterized population-based study of 5,675 patients after CRC diagnosis in Scotland. None of the genetic risk variants were associated with either overall survival (OS) or CRC-specific survival. Next, we combined the variants in a polygenic risk score, but again we observed no association between survival outcome and overall genetic susceptibility to CRC risk-as defined by common genetic variants (OS: hazard ratio = 1.00, 95% confidence interval = 0.96-1.05). Furthermore, we found no incremental increase in the discriminative performance when adding these genetic variants to the baseline CRC-survival predictive model of age, sex and stage at diagnosis. Given that our study is well-powered (>0.88) to detect effects on survival for 74% of the variants, we conclude that effects of common variants associated with CRC risk which have been identified to date are unlikely to have clinically relevant effect on survival outcomes for patients diagnosed with CRC.