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Evaluation of Association of HNF1B Variants with Diverse Cancers: Collaborative Analysis of Data from 19 Genome-Wide Association Studies

Author

Listed:
  • Katherine S Elliott
  • Eleftheria Zeggini
  • Mark I McCarthy
  • Julius Gudmundsson
  • Patrick Sulem
  • Simon N Stacey
  • Steinunn Thorlacius
  • Laufey Amundadottir
  • Henrik Grönberg
  • Jianfeng Xu
  • Valerie Gaborieau
  • Rosalind A Eeles
  • David E Neal
  • Jenny L Donovan
  • Freddie C Hamdy
  • Kenneth Muir
  • Shih-Jen Hwang
  • Margaret R Spitz
  • Brent Zanke
  • Luis Carvajal-Carmona
  • Kevin M Brown
  • Australian Melanoma Family Study Investigators
  • Nicholas K Hayward
  • Stuart Macgregor
  • Ian P M Tomlinson
  • Mathieu Lemire
  • Christopher I Amos
  • Joanne M Murabito
  • William B Isaacs
  • Douglas F Easton
  • Paul Brennan
  • The PanScan Consortium
  • Rosa B Barkardottir
  • Daniel F Gudbjartsson
  • Thorunn Rafnar
  • David J Hunter
  • Stephen J Chanock
  • Kari Stefansson
  • John P A Ioannidis

Abstract

Background: Genome-wide association studies have found type 2 diabetes-associated variants in the HNF1B gene to exhibit reciprocal associations with prostate cancer risk. We aimed to identify whether these variants may have an effect on cancer risk in general versus a specific effect on prostate cancer only. Methodology/Principal Findings: In a collaborative analysis, we collected data from GWAS of cancer phenotypes for the frequently reported variants of HNF1B, rs4430796 and rs7501939, which are in linkage disequilibrium (r2 = 0.76, HapMap CEU). Overall, the analysis included 16 datasets on rs4430796 with 19,640 cancer cases and 21,929 controls; and 21 datasets on rs7501939 with 26,923 cases and 49,085 controls. Malignancies other than prostate cancer included colorectal, breast, lung and pancreatic cancers, and melanoma. Meta-analysis showed large between-dataset heterogeneity that was driven by different effects in prostate cancer and other cancers. The per-T2D-risk-allele odds ratios (95% confidence intervals) for rs4430796 were 0.79 (0.76, 0.83)] per G allele for prostate cancer (p

Suggested Citation

  • Katherine S Elliott & Eleftheria Zeggini & Mark I McCarthy & Julius Gudmundsson & Patrick Sulem & Simon N Stacey & Steinunn Thorlacius & Laufey Amundadottir & Henrik Grönberg & Jianfeng Xu & Valerie G, 2010. "Evaluation of Association of HNF1B Variants with Diverse Cancers: Collaborative Analysis of Data from 19 Genome-Wide Association Studies," PLOS ONE, Public Library of Science, vol. 5(5), pages 1-8, May.
    • Handle: RePEc:plo:pone00:0010858
    DOI: 10.1371/journal.pone.0010858
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