rs4939827

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.

Genome-wide investigation of gene-environment interactions in colorectal cancer using a two-tiered case-only/case-control design. In 314 sporadic CRC cases (stage I) and 259 familial CRC cases plus 1,002 controls (stage II), rs1944511 showed a significant interaction with overweight (OR=2.00, p=0.042 after multiple testing correction). Several other SNPs showed nominally significant G×E interactions with overweight, smoking, and alcohol consumption. Among candidate CRC-associated SNPs, rs9929218 showed the strongest interaction with alcohol consumption (nominal p=0.008).

Meta-analysis of genome-wide association studies examining colorectal cancer susceptibility in 2,906 cases and 3,416 controls (GWAS) with replication in 8,161 cases and 9,101 controls. Eight of ten previously identified SNPs showed associations (p-values 0.02 to 1.8×10⁻⁸), and the study identified marginal evidence for a second independent signal in BMP2 (rs4813802, combined p=7.3×10⁻⁵) and a novel association with TERT-CLPTM1L (rs2853668, combined p=1.9×10⁻⁴).

This population-based study examined 727 post-menopausal women with colorectal cancer and found that SMAD7 variants rs4939827 and rs4464148 were associated with cancer-specific survival, but only among pre-diagnostic NSAID users. Among NSAID users with non-metastatic disease, the minor allele of rs4939827 was associated with worse survival (HR=2.67, 95% CI: 1.33-5.37), while the minor allele of rs4464148 was associated with better survival (HR=0.41, 95% CI: 0.18-0.94).