Common genetic variation and survival after colorectal cancer diagnosis: a genome-wide analysis
Year: 2015
Type: article
Study design: Observational Study
Abstract: Genome-wide association studies have identified several germline single nucleotide polymorphisms (SNPs) significantly associated with colorectal cancer (CRC) incidence. Common germline genetic variation may also be related to CRC survival. We used a discovery-based approach to identify SNPs related to survival outcomes after CRC diagnosis. Genome-wide genotyping arrays were conducted for 3494 individuals with invasive CRC enrolled in six prospective cohort studies (median study-specific follow-up = 4.2-8.1 years). In pooled analyses, we used Cox regression to assess SNP-specific associations with CRC-specific and overall survival, with additional analyses stratified by stage at diagnosis. Top findings were followed-up in independent studies. A P value threshold of P < 5×10(-8) in analyses combining discovery and follow-up studies was required for genome-wide significance. Among individuals with distant-metastatic CRC, several SNPs at 6p12.1, nearest the ELOVL5 gene, were statistically significantly associated with poorer survival, with the strongest associations noted for rs209489 [hazard ratio (HR) = 1.8, P = 7.6×10(-10) and HR = 1.8, P = 3.7×10(-9) for CRC-specific and overall survival, respectively). No SNPs were statistically significantly associated with survival among all cases combined or in cases without distant-metastases. SNPs in 6p12.1/ELOVL5 were associated with survival outcomes in individuals with distant-metastatic CRC, and merit further follow-up for functional significance. Findings from this genome-wide association study highlight the potential importance of genetic variation in CRC prognosis and provide clues to genomic regions of potential interest.
Source: Carcinogenesis
Authors: Amanda I. Phipps, Michael N. Passarelli, Andrew T. Chan, Tabitha A. Harrison, Jihyoun Jeon, Carolyn M. Hutter, Sonja I. Berndt, Hermann Brenner, Bette J. Caan, Peter T. Campbell, Jenny Chang-Claude, Stephen J. Chanock, Jeremy P. Cheadle, Keith R. Curtis, David Duggan, David Fisher, Charles S. Fuchs, Manish Gala, Edward L. Giovannucci, Richard B. Hayes, Michael Hoffmeister, Li Hsu, Eric J. Jacobs, Lina Jansen, Richard Kaplan, Elisabeth J. Kap, Timothy S. Maughan, John D. Potter, Robert E. Schoen, Daniela Seminara, Martha L. Slattery, Hannah West, Emily White, Ulrike Peters, Polly A. Newcomb
Institutions: University of Washington, Fred Hutch Cancer Center, Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, German Cancer Research Center, Deutsches Konsortium für Translationale Krebsforschung, Kaiser Permanente, Kaiser Permanente Northern California, American Cancer Society, Cardiff University, Translational Genomics Research Institute, MRC Clinical Trials Unit at UCL, University College London, Dana-Farber Cancer Institute, New York University, University of Oxford, CRUK/MRC Oxford Institute for Radiation Oncology, Massey University, University of Pittsburgh, University of Pittsburgh Medical Center, University of Utah, University of Utah Health Care
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: FHCRC High-Performance Computing Cluster, Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, G1327305488, Transdisciplinary Studies of Genetic Variation in Colorectal Cancer, G1936416099, Diet, Activity, and Lifestyle as a Risk Factor for Colorectal Cancer, G24053502, Training and Research in Colon Cancer Survival, Inflammation and Colorectal Neoplasia, G2883192542, Genome-Wide Association Study of Nonsynonymous SNPs in Colon Cancer, G3061211801, G3177554543, Established Investigator Award Anti-Inflammatory Exposures in Cancer Prevention, Dietary and Hormonal Determinants of Cancer in Women, G46527388, G499732063, G6243209542, Mentored Patient-Oriented Research in Digestive Diseases, Lifestyle Factors and Survival Outcomes for Colorectal Cancer Molecular Subtypes, Prospective Studies of Diet and Cancer in Men and Women, Cancer Epidemiology Cohort in Male Health Professionals, G806099689, G915193561
OpenAlex ID: W2175332478