- Labadie, Julia D;
- Savas, Sevtap;
- Harrison, Tabitha A;
- Banbury, Barb;
- Huang, Yuhan;
- Buchanan, Daniel D;
- Campbell, Peter T;
- Gallinger, Steven J;
- Giles, Graham G;
- Gunter, Marc J;
- Hoffmeister, Michael;
- Hsu, Li;
- Jenkins, Mark A;
- Lin, Yi;
- Ogino, Shuji;
- Phipps, Amanda I;
- Slattery, Martha L;
- Steinfelder, Robert S;
- Sun, Wei;
- Van Guelpen, Bethany;
- Hua, Xinwei;
- Figuieredo, Jane C;
- Pai, Rish K;
- Nassir, Rami;
- Qi, Lihong;
- Chan, Andrew T;
- Peters, Ulrike;
- Newcomb, Polly A
Identification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies. Approximately 7.5 million SNPs were examined under the log-additive model using Cox proportional hazards models, adjusting for clinical factors and principal components. Additionally, we ran secondary analyses stratifying by tumor site and disease stage. We used a genome-wide p-value threshold of 5 × 10-8 to assess statistical significance. No variants were statistically significantly associated with disease-specific survival in the full case analysis or in the stage-stratified analyses. Three SNPs were statistically significantly associated with disease-specific survival for cases with tumors located in the distal colon (rs698022, HR = 1.48, CI 1.30-1.69, p = 8.47 × 10-9) and the proximal colon (rs189655236, HR = 2.14, 95% CI 1.65-2.77, p = 9.19 × 10-9 and rs144717887, HR = 2.01, 95% CI 1.57-2.58, p = 3.14 × 10-8), whereas no associations were detected for rectal tumors. Findings from this large genome-wide association study highlight the potential for anatomical-site-stratified genome-wide studies to identify germline genetic risk variants associated with colorectal cancer-specific survival. Larger sample sizes and further replication efforts are needed to more fully interpret these findings.