Skip to main content
Open Access Publications from the University of California

UC Davis

UC Davis Previously Published Works bannerUC Davis

Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies.

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


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 (r(2) = 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<10(-15) for both); and 1.03 (0.99, 1.07) for all other cancers. Similarly for rs7501939 the per-T2D-risk-allele odds ratios (95% confidence intervals) were 0.80 (0.77, 0.83) per T allele for prostate cancer (p<10(-15) for both); and 1.00 (0.97, 1.04) for all other cancers. No malignancy other than prostate cancer had a nominally statistically significant association.


The examined HNF1B variants have a highly specific effect on prostate cancer risk with no apparent association with any of the other studied cancer types.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View