Human Genetics

, Volume 131, Issue 2, pp 217–234

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

  • Ulrike Peters
  • Carolyn M. Hutter
  • Li Hsu
  • Fredrick R. Schumacher
  • David V. Conti
  • Christopher S. Carlson
  • Christopher K. Edlund
  • Robert W. Haile
  • Steven Gallinger
  • Brent W. Zanke
  • Mathieu Lemire
  • Jagadish Rangrej
  • Raakhee Vijayaraghavan
  • Andrew T. Chan
  • Aditi Hazra
  • David J. Hunter
  • Jing Ma
  • Charles S. Fuchs
  • Edward L. Giovannucci
  • Peter Kraft
  • Yan Liu
  • Lin Chen
  • Shuo Jiao
  • Karen W. Makar
  • Darin Taverna
  • Stephen B. Gruber
  • Gad Rennert
  • Victor Moreno
  • Cornelia M. Ulrich
  • Michael O. Woods
  • Roger C. Green
  • Patrick S. Parfrey
  • Ross L. Prentice
  • Charles Kooperberg
  • Rebecca D. Jackson
  • Andrea Z. LaCroix
  • Bette J. Caan
  • Richard B. Hayes
  • Sonja I. Berndt
  • Stephen J. Chanock
  • Robert E. Schoen
  • Jenny Chang-Claude
  • Michael Hoffmeister
  • Hermann Brenner
  • Bernd Frank
  • Stéphane Bézieau
  • Sébastien Küry
  • Martha L. Slattery
  • John L. Hopper
  • Mark A. Jenkins
  • Loic Le Marchand
  • Noralane M. Lindor
  • Polly A. Newcomb
  • Daniela Seminara
  • Thomas J. Hudson
  • David J. Duggan
  • John D. Potter
  • Graham Casey
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

Authors and Affiliations

  • Ulrike Peters
    • 1
    • 2
  • Carolyn M. Hutter
    • 1
  • Li Hsu
    • 3
  • Fredrick R. Schumacher
    • 4
  • David V. Conti
    • 4
  • Christopher S. Carlson
    • 1
  • Christopher K. Edlund
    • 5
  • Robert W. Haile
    • 4
  • Steven Gallinger
    • 6
  • Brent W. Zanke
    • 7
  • Mathieu Lemire
    • 8
  • Jagadish Rangrej
    • 8
  • Raakhee Vijayaraghavan
    • 9
  • Andrew T. Chan
    • 10
    • 11
  • Aditi Hazra
    • 11
    • 12
  • David J. Hunter
    • 12
  • Jing Ma
    • 11
  • Charles S. Fuchs
    • 11
    • 13
  • Edward L. Giovannucci
    • 11
    • 14
  • Peter Kraft
    • 12
  • Yan Liu
    • 15
  • Lin Chen
    • 16
  • Shuo Jiao
    • 1
  • Karen W. Makar
    • 1
  • Darin Taverna
    • 9
  • Stephen B. Gruber
    • 17
  • Gad Rennert
    • 18
  • Victor Moreno
    • 19
  • Cornelia M. Ulrich
    • 1
    • 2
    • 20
  • Michael O. Woods
    • 21
  • Roger C. Green
    • 21
  • Patrick S. Parfrey
    • 22
  • Ross L. Prentice
    • 23
  • Charles Kooperberg
    • 23
  • Rebecca D. Jackson
    • 24
  • Andrea Z. LaCroix
    • 1
  • Bette J. Caan
    • 25
  • Richard B. Hayes
    • 26
  • Sonja I. Berndt
    • 27
  • Stephen J. Chanock
    • 27
  • Robert E. Schoen
    • 28
  • Jenny Chang-Claude
    • 29
  • Michael Hoffmeister
    • 30
  • Hermann Brenner
    • 30
  • Bernd Frank
    • 30
  • Stéphane Bézieau
    • 31
  • Sébastien Küry
    • 31
  • Martha L. Slattery
    • 32
  • John L. Hopper
    • 33
  • Mark A. Jenkins
    • 33
  • Loic Le Marchand
    • 34
  • Noralane M. Lindor
    • 35
  • Polly A. Newcomb
    • 1
  • Daniela Seminara
    • 36
  • Thomas J. Hudson
    • 8
    • 37
  • David J. Duggan
    • 9
  • John D. Potter
    • 2
    • 23
  • Graham Casey
    • 4
  1. 1.Cancer Prevention ProgramFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of Epidemiology, School of Public HealthUniversity of WashingtonSeattleUSA
  3. 3.Biostatistics and Biomathematics ProgramFred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  6. 6.Department of Surgery, Toronto General HospitalUniversity Health NetworkTorontoCanada
  7. 7.Clinical Epidemiology ProgramOttawa Hospital Research InstituteOttawaCanada
  8. 8.Ontario Institute for Cancer ResearchTorontoCanada
  9. 9.Translational Genomics Research InstitutePhoenixUSA
  10. 10.Division of Gastroenterology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  11. 11.Channing LaboratoryBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  12. 12.Program in Molecular and Genetic Epidemiology, Department of EpidemiologyHarvard School of Public HealthBostonUSA
  13. 13.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  14. 14.Departments of Epidemiology and NutritionHarvard School of Public HealthBostonUSA
  15. 15.Dallas Research CenterStephens & AssociatesDallasUSA
  16. 16.Department of Health StudiesUniversity of ChicagoChicagoUSA
  17. 17.Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  18. 18.Department of Community Medicine and EpidemiologyCarmel Medical Center and Technion Faculty of MedicineHaifaIsrael
  19. 19.Biostatistics and Bioinformatics UnitCatalan Institute of Oncology-IDIBELLBarcelonaSpain
  20. 20.Division of Preventive OncologyGerman Cancer Research CenterHeidelbergGermany
  21. 21.Discipline of Genetics, Faculty of MedicineMemorial University of NewfoundlandSt. John’sCanada
  22. 22.Discipline of Medicine, Faculty of MedicineMemorial University of NewfoundlandSt. John’sCanada
  23. 23.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  24. 24.Division of Endocrinology, Diabetes and MetabolismOhio State UniversityColumbusUSA
  25. 25.Division of ResearchKaiser Permanente Medical Care ProgramOaklandUSA
  26. 26.Division of Epidemiology, Department of Environmental MedicineNew York University School of MedicineNew YorkUSA
  27. 27.Division of Cancer Epidemiology and Genetics, Department of Health and Human ServicesNational Cancer Institute, National Institutes of HealthBethesdaUSA
  28. 28.Department of EpidemiologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  29. 29.Division of Cancer EpidemiologyGerman Cancer Research CenterHeidelbergGermany
  30. 30.Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research CenterHeidelbergGermany
  31. 31.Service de Génétique Médicale, Pôle de BiologieCentre Hospitalier Universitaire (CHU) de NantesNantesFrance
  32. 32.Department of Internal MedicineUniversity of Utah Health Sciences CenterSalt Lake CityUSA
  33. 33.Centre for Molecular, Environmental, Genetic, and Analytical EpidemiologyUniversity of MelbourneMelbourneAustralia
  34. 34.Epidemiology Program, Cancer Research Center of Hawai’iUniversity of Hawai’i at ManoaHonoluluUSA
  35. 35.Department of Medical GeneticsMayo ClinicRochesterUSA
  36. 36.Division of Cancer Control and Population SciencesNational Cancer InstituteBethesdaUSA
  37. 37.Departments of Medical Biophysics and Molecular GeneticsUniversity of TorontoTorontoCanada