Genetic Variation in Circadian Genes and Survival in Patients with CRC

Abstract

Disruption of circadian rhythm, characterized by sleep/activity pattern disturbances, is associated with an elevated risk of developing CRC as well as poor prognosis in patients with various cancers. To examine the relationship of single nucleotide polymorphisms (SNPs) in circadian genes and chronotype-associated SNPs with CRC specific survival and overall survival in patients with CRC, we used data from 16 studies participating in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) (N=17,550 participants). The results identified 8 variants with modest increased hazard ratios (HRs) in analyses of CRC survival overall and one SNP located on RORA (rs1869486 HR = 1.8, CI 1.2–2.7, p = 0.004) that was statistically significantly associated with disease-specific survival in patients with stage 0/1 tumors. None of these associations remained significant after adjusting for multiple comparisons. Overall, our study finds that the underlying germline variation in the circadian clock pathway, captured by the selected SNPs within circadian genes and chronotype variants, is not statistically significantly associated with survival outcomes after CRC diagnosis.