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Genome-wide association study identifies tumor anatomical site-specific risk variants for colorectal cancer survival.
Pubmed ID
34996992 (View this publication on the PubMed website)
Digital Object Identifier
Sci Rep. 2022 Jan 7; Volume 12 (Issue 1): Pages 127
Labadie JD , Savas S , Harrison TA , Banbury B , Huang Y , Buchanan DD , Campbell PT , Gallinger SJ , Giles GG , Gunter MJ , Hoffmeister M , Hsu L , Jenkins MA , Lin Y , Ogino S , Phipps AI , Slattery ML , Steinfelder RS , Sun W , Van Guelpen B , more Hua X , Figuieredo JC , Pai RK , Nassir R , Qi L , Chan AT , Peters U , Newcomb PA
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Discipline of Genetics, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
  • Department of Population Science, American Cancer Society, Atlanta, GA, USA.
  • Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
  • Nutrition and Metabolism Section, International Agency for Research On Cancer, World Health Organization, Lyon, France.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA.
  • Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. more
  • Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Department of Pathology, School of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
  • Department of Public Health Sciences, University of California Davis, Davis, CA, USA.
  • Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

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.

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