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Human Genetics

, Volume 134, Issue 4, pp 439–450 | Cite as

Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases

  • Brian T. Helfand
  • Kimberly A. Roehl
  • Phillip R. Cooper
  • Barry B. McGuire
  • Liesel M. Fitzgerald
  • Geraldine Cancel-Tassin
  • Jean-Nicolas Cornu
  • Scott Bauer
  • Erin L. Van Blarigan
  • Xin Chen
  • David Duggan
  • Elaine A. Ostrander
  • Mary Gwo-Shu
  • Zuo-Feng Zhang
  • Shen-Chih Chang
  • Somee Jeong
  • Elizabeth T. H. Fontham
  • Gary Smith
  • James L. Mohler
  • Sonja I. Berndt
  • Shannon K. McDonnell
  • Rick Kittles
  • Benjamin A. Rybicki
  • Matthew Freedman
  • Philip W. Kantoff
  • Mark Pomerantz
  • Joan P. Breyer
  • Jeffrey R. Smith
  • Timothy R. Rebbeck
  • Dan Mercola
  • William B. Isaacs
  • Fredrick Wiklund
  • Olivier Cussenot
  • Stephen N. Thibodeau
  • Daniel J. Schaid
  • Lisa Cannon-Albright
  • Kathleen A. Cooney
  • Stephen J. Chanock
  • Janet L. Stanford
  • June M. Chan
  • John Witte
  • Jianfeng Xu
  • Jeannette T. Bensen
  • Jack A. Taylor
  • William J. CatalonaEmail author
Original Investigation

Abstract

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69–0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68–0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58–0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54–0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness.

Keywords

Prostate Cancer Gleason Score Aggressive Disease Prostate Cancer Risk European Ancestry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

439_2015_1534_MOESM1_ESM.docx (115 kb)
Supplementary material 1 (DOCX 115 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Brian T. Helfand
    • 1
  • Kimberly A. Roehl
    • 2
  • Phillip R. Cooper
    • 2
  • Barry B. McGuire
    • 2
  • Liesel M. Fitzgerald
    • 3
  • Geraldine Cancel-Tassin
    • 4
  • Jean-Nicolas Cornu
    • 4
  • Scott Bauer
    • 5
  • Erin L. Van Blarigan
    • 5
  • Xin Chen
    • 6
  • David Duggan
    • 7
  • Elaine A. Ostrander
    • 8
  • Mary Gwo-Shu
    • 9
  • Zuo-Feng Zhang
    • 10
  • Shen-Chih Chang
    • 10
  • Somee Jeong
    • 10
  • Elizabeth T. H. Fontham
    • 11
  • Gary Smith
    • 12
  • James L. Mohler
    • 12
  • Sonja I. Berndt
    • 13
  • Shannon K. McDonnell
    • 14
  • Rick Kittles
    • 15
  • Benjamin A. Rybicki
    • 16
  • Matthew Freedman
    • 17
  • Philip W. Kantoff
    • 17
  • Mark Pomerantz
    • 18
  • Joan P. Breyer
    • 19
  • Jeffrey R. Smith
    • 19
  • Timothy R. Rebbeck
    • 20
  • Dan Mercola
    • 6
  • William B. Isaacs
    • 21
  • Fredrick Wiklund
    • 22
  • Olivier Cussenot
    • 4
  • Stephen N. Thibodeau
    • 23
  • Daniel J. Schaid
    • 14
  • Lisa Cannon-Albright
    • 24
  • Kathleen A. Cooney
    • 25
  • Stephen J. Chanock
    • 26
  • Janet L. Stanford
    • 27
  • June M. Chan
    • 5
  • John Witte
    • 5
  • Jianfeng Xu
    • 28
  • Jeannette T. Bensen
    • 29
  • Jack A. Taylor
    • 30
  • William J. Catalona
    • 2
    Email author
  1. 1.Department of Surgery, Division of UrologyJohn and Carol Walter Center for Urological Health, NorthShore University Health SystemEvanstonUSA
  2. 2.Department of UrologyNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Cancer Epidemiology CentreCancer Council VictoriaMelbourneAustralia
  4. 4.CeRePP ICPCG Group, Hopital TenonAssistance Publique-Hopitaux de ParisParisFrance
  5. 5.Genome Analysis Core Facility, Helen Diller Family Comprehensive Cancer CenterUniversity of CaliforniaSan FranciscoUSA
  6. 6.Department of Pathology and Laboratory MedicineUniversity of CaliforniaIrvineUSA
  7. 7.Integrated Cancer Genomics DivisionTGenPhoenixUSA
  8. 8.Cancer Genetics BranchNational Human Genome Research InstituteBethesdaUSA
  9. 9.Department of Medical OncologyDana-Farber Cancer Institute and Harvard Medical SchoolBostonUSA
  10. 10.Department of Epidemiology, Fielding School of Public HealthUniversity of CaliforniaLos AngelesUSA
  11. 11.School of Public HealthLouisiana State University Health Sciences CenterNew OrleansUSA
  12. 12.Department of UrologyRoswell Park Cancer InstituteBuffaloUSA
  13. 13.Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology BranchNational Cancer InstituteBethesdaUSA
  14. 14.Department of Health Sciences ResearchMayo ClinicRochesterUSA
  15. 15.Department of Surgery, Division of UrologyUniversity of ArizonaTucsonUSA
  16. 16.Department of Public Health SciencesHenry Ford Health SystemDetroitUSA
  17. 17.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  18. 18.Lank Center for Genitourinary OncologyDana-Farber Cancer Institute and Harvard Medical SchoolBostonUSA
  19. 19.Department of Medicine, Vanderbilt-Ingram Cancer CenterVanderbilt University School of MedicineNashvilleUSA
  20. 20.Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  21. 21.Department of UrologyJohns Hopkins UniversityBaltimoreUSA
  22. 22.University of Umeå ICPCG GroupUmeåSweden
  23. 23.Department of Lab Medicine and PathologyMayo ClinicRochesterUSA
  24. 24.Division of Genetic Epidemiology, Department of MedicineUniversity of Utah School of MedicineSalt Lake CityUSA
  25. 25.Department of Urology, Department of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA
  26. 26.Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleUSA
  27. 27.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  28. 28.Program for Personalized Cancer Care and Department of SurgeryNorthShore University Health SystemEvanstonUSA
  29. 29.Gillings School of Global Public Health Department of Epidemiology and Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  30. 30.Epidemiology Branch and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health SciencesResearch Triangle ParkDurhamUSA

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