(2010) Evaluation of association of HNF1B variants with diverse cancers : collaborative analysis of data from 19 genome-wide association studies. PLoS One, Vol.5 (No.5). e10858. doi:10.1371/journal.pone.0010858

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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<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.

Conclusions/Significance
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.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Prostate -- Cancer, Non-insulin-dependent diabetes, Cancer -- Susceptibility
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	28 May 2010
Dates:	Date Event 28 May 2010 Published
Volume:	Vol.5
Number:	No.5
Number of Pages:	8
Page Range:	e10858
DOI:	10.1371/journal.pone.0010858
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	National Institutes of Health (U.S.) (NIH), Wellcome Trust (London, England), National Health and Medical Research Council (Australia) (NHMRC), Cancerfonden, Sweden. Vetenskapsrådet [Research Council], Cancer Research UK (CRUK), National Cancer Research Institute (NCRI), Medical Research Council (Great Britain) (MRC)
Grant number:	UL1 RR025752 (NIH), R01-CA88363 (NIH), WT075491/Z/04 (WT), WT088885/Z/09/Z (WT), C5047/A8385 (CRUK), C5047/A7357 (CRUK)

Data sourced from Thomson Reuters' Web of Knowledge

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