A Comprehensive Study of the Effect on Colorectal Cancer Survival of Common Germline Genetic Variation Previously Linked with Cancer Prognosis

Background: Germline genetic variants may influence pathways of tumor progression common to multiple cancer types. Here, we investigated the association between survival after colorectal cancer diagnosis and 128 common genetic variants previously associated with prognosis in genome-wide association studies in different cancer types. Methods: We studied survival outcomes in a large well-documented, prospective, population-based cohort (5,675 patients with colorectal cancer) with up to 20 years' follow-up. Results: None of the 128 variants were significantly associated with overall or colorectal cancer–specific survival (P < 5 × 10^-4, Bonferroni-corrected threshold). We observed suggestive evidence (P < 0.05) for eight variants (rs17026425, rs17057166, rs6854845, rs1728400, rs17693104, rs202280, rs6797464, and rs823920) in all colorectal cancer and two variants (rs17026425 and rs6854845) in rectal cancer that were concordant with previous reports. Conclusions: Given good statistical power (>0.80 for 75% of variants), this study indicates that most previously reported variants associated with cancer survival have limited influence on colorectal cancer prognosis. Impact: Although small effects cannot be excluded, clinically meaningful germline influences on patients with colorectal cancer as a group are unlikely.