Genome-wide association study identifies tumor anatomical site-specific risk variants for colorectal cancer survival.

Abstract

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.

• Authors: Julia D Labadie, Sevtap Savas, Tabitha A Harrison, Barb Banbury, Yuhan Huang, Daniel D Buchanan, Peter T Campbell, Steven J Gallinger, Graham G Giles, Marc J Gunter, Michael Hoffmeister, Li Hsu, Mark A Jenkins, Yi Lin, Shuji Ogino, Amanda I Phipps, Martha L Slattery, Robert S Steinfelder, Wei Sun, Bethany Van Guelpen, Xinwei Hua, Jane C Figuieredo, Rish K Pai, Rami Nassir, Lihong Qi, Andrew T Chan, Ulrike Peters, Polly A Newcomb
• Journal: Scientific reports (Sci Rep) Vol. 12 Issue 1 Pg. 127 (01 07 2022) ISSN: 2045-2322 [Electronic] England
• PMID: 34996992 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Colorectal Neoplasms (genetics, mortality, pathology, therapy)
• Databases, Genetic
• Female
• Genetic Loci
• Genome-Wide Association Study
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Polymorphism, Single Nucleotide
• Risk Assessment
• Risk Factors
• Young Adult