Human Genetics

, Volume 131, Issue 2, pp 217–234

Meta-analysis of new genome-wide association studies of colorectal cancer risk

Authors

    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
    • Department of Epidemiology, School of Public HealthUniversity of Washington
  • Carolyn M. Hutter
    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
  • Li Hsu
    • Biostatistics and Biomathematics ProgramFred Hutchinson Cancer Research Center
  • Fredrick R. Schumacher
    • Department of Preventive Medicine, Keck School of MedicineUniversity of Southern California
  • David V. Conti
    • Department of Preventive Medicine, Keck School of MedicineUniversity of Southern California
  • Christopher S. Carlson
    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
  • Christopher K. Edlund
    • Keck School of MedicineUniversity of Southern California
  • Robert W. Haile
    • Department of Preventive Medicine, Keck School of MedicineUniversity of Southern California
  • Steven Gallinger
    • Department of Surgery, Toronto General HospitalUniversity Health Network
  • Brent W. Zanke
    • Clinical Epidemiology ProgramOttawa Hospital Research Institute
  • Mathieu Lemire
    • Ontario Institute for Cancer Research
  • Jagadish Rangrej
    • Ontario Institute for Cancer Research
  • Raakhee Vijayaraghavan
    • Translational Genomics Research Institute
  • Andrew T. Chan
    • Division of Gastroenterology, Massachusetts General HospitalHarvard Medical School
    • Channing LaboratoryBrigham and Women’s Hospital and Harvard Medical School
  • Aditi Hazra
    • Channing LaboratoryBrigham and Women’s Hospital and Harvard Medical School
    • Program in Molecular and Genetic Epidemiology, Department of EpidemiologyHarvard School of Public Health
  • David J. Hunter
    • Program in Molecular and Genetic Epidemiology, Department of EpidemiologyHarvard School of Public Health
  • Jing Ma
    • Channing LaboratoryBrigham and Women’s Hospital and Harvard Medical School
  • Charles S. Fuchs
    • Channing LaboratoryBrigham and Women’s Hospital and Harvard Medical School
    • Department of Medical OncologyDana-Farber Cancer Institute
  • Edward L. Giovannucci
    • Channing LaboratoryBrigham and Women’s Hospital and Harvard Medical School
    • Departments of Epidemiology and NutritionHarvard School of Public Health
  • Peter Kraft
    • Program in Molecular and Genetic Epidemiology, Department of EpidemiologyHarvard School of Public Health
  • Yan Liu
    • Dallas Research CenterStephens & Associates
  • Lin Chen
    • Department of Health StudiesUniversity of Chicago
  • Shuo Jiao
    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
  • Karen W. Makar
    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
  • Darin Taverna
    • Translational Genomics Research Institute
  • Stephen B. Gruber
    • Department of Internal MedicineUniversity of Michigan
  • Gad Rennert
    • Department of Community Medicine and EpidemiologyCarmel Medical Center and Technion Faculty of Medicine
  • Victor Moreno
    • Biostatistics and Bioinformatics UnitCatalan Institute of Oncology-IDIBELL
  • Cornelia M. Ulrich
    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
    • Department of Epidemiology, School of Public HealthUniversity of Washington
    • Division of Preventive OncologyGerman Cancer Research Center
  • Michael O. Woods
    • Discipline of Genetics, Faculty of MedicineMemorial University of Newfoundland
  • Roger C. Green
    • Discipline of Genetics, Faculty of MedicineMemorial University of Newfoundland
  • Patrick S. Parfrey
    • Discipline of Medicine, Faculty of MedicineMemorial University of Newfoundland
  • Ross L. Prentice
    • Division of Public Health SciencesFred Hutchinson Cancer Research Center
  • Charles Kooperberg
    • Division of Public Health SciencesFred Hutchinson Cancer Research Center
  • Rebecca D. Jackson
    • Division of Endocrinology, Diabetes and MetabolismOhio State University
  • Andrea Z. LaCroix
    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
  • Bette J. Caan
    • Division of ResearchKaiser Permanente Medical Care Program
  • Richard B. Hayes
    • Division of Epidemiology, Department of Environmental MedicineNew York University School of Medicine
  • Sonja I. Berndt
    • Division of Cancer Epidemiology and Genetics, Department of Health and Human ServicesNational Cancer Institute, National Institutes of Health
  • Stephen J. Chanock
    • Division of Cancer Epidemiology and Genetics, Department of Health and Human ServicesNational Cancer Institute, National Institutes of Health
  • Robert E. Schoen
    • Department of EpidemiologyUniversity of Pittsburgh Medical Center
  • Jenny Chang-Claude
    • Division of Cancer EpidemiologyGerman Cancer Research Center
  • Michael Hoffmeister
    • Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research Center
  • Hermann Brenner
    • Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research Center
  • Bernd Frank
    • Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research Center
  • Stéphane Bézieau
    • Service de Génétique Médicale, Pôle de BiologieCentre Hospitalier Universitaire (CHU) de Nantes
  • Sébastien Küry
    • Service de Génétique Médicale, Pôle de BiologieCentre Hospitalier Universitaire (CHU) de Nantes
  • Martha L. Slattery
    • Department of Internal MedicineUniversity of Utah Health Sciences Center
  • John L. Hopper
    • Centre for Molecular, Environmental, Genetic, and Analytical EpidemiologyUniversity of Melbourne
  • Mark A. Jenkins
    • Centre for Molecular, Environmental, Genetic, and Analytical EpidemiologyUniversity of Melbourne
  • Loic Le Marchand
    • Epidemiology Program, Cancer Research Center of Hawai’iUniversity of Hawai’i at Manoa
  • Noralane M. Lindor
    • Department of Medical GeneticsMayo Clinic
  • Polly A. Newcomb
    • Cancer Prevention ProgramFred Hutchinson Cancer Research Center
  • Daniela Seminara
    • Division of Cancer Control and Population SciencesNational Cancer Institute
  • Thomas J. Hudson
    • Ontario Institute for Cancer Research
    • Departments of Medical Biophysics and Molecular GeneticsUniversity of Toronto
  • David J. Duggan
    • Translational Genomics Research Institute
  • John D. Potter
    • Department of Epidemiology, School of Public HealthUniversity of Washington
    • Division of Public Health SciencesFred Hutchinson Cancer Research Center
    • Department of Preventive Medicine, Keck School of MedicineUniversity of Southern California
Original Investigation

DOI: 10.1007/s00439-011-1055-0

Cite this article as:
Peters, U., Hutter, C.M., Hsu, L. et al. Hum Genet (2012) 131: 217. doi:10.1007/s00439-011-1055-0

Abstract

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10−8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10−5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10−4). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.

Supplementary material

439_2011_1055_MOESM1_ESM.doc (2.7 mb)
Supplementary material 1 (DOC 2,798 kb)

Copyright information

© Springer-Verlag 2011