rs6691170

This study analyzes 243 rectal cancer patients to determine if colorectal cancer (CRC) susceptibility SNPs are associated with rectal cancer prognosis. SNPs on 8q24 (rs6983267 near MYC), 18q21 (rs12953717, rs4464148 in SMAD7), and 20q13 (rs4925386 in LAMA5) are found to be associated with disease-free survival and overall survival in rectal cancer patients, with some alleles associated with better or worse prognosis despite their effects on CRC risk.

This case-control study in Japanese population evaluated CRC risk prediction models using SNPs identified in European and East Asian GWAS. An 11-SNP model combining 6 European-identified SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) with 5 East Asian-identified SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) showed significantly improved discrimination capacity compared to a 6-SNP model alone (derivation AUC 0.6392 vs 0.6125, P=0.0039; replication AUC 0.5695 vs 0.5310, P=0.0018), with cumulative risk at age 80 estimated at 13% in high-risk versus 6% in low-risk genetic groups.

A two-stage genome-wide association study (GWAS) in 19,179 East Asian individuals identified rs7229639 in the SMAD7 gene as a new colorectal cancer (CRC) risk variant with odds ratio (OR) = 1.22 (95% CI: 1.15-1.29, P = 2.93×10^-11). This novel variant is independent of previously reported CRC risk variants (rs4939827, rs58920878, rs12953717, rs4464148) in this region and explains approximately 0.75% of familial CRC risk in East Asians.