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Title: Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies.
Authors: Elliott KS,  Zeggini E,  McCarthy MI,  Gudmundsson J,  Sulem P,  Stacey SN,  Thorlacius S,  Amundadottir L,  Grönberg H,  Xu J,  Gaborieau V,  Eeles RA,  Neal DE,  Donovan JL,  Hamdy FC,  Muir K,  Hwang SJ,  Spitz MR,  Zanke B,  Carvajal-Carmona L,  Brown KM,  Australian Melanoma Family Study Investigators,  Hayward NK,  Macgregor S,  Tomlinson IP,  Lemire M,  Amos CI,  Murabito JM,  Isaacs WB,  Easton DF,  Brennan P,  PanScan Consortium,  Barkardottir RB,  Gudbjartsson DF,  Rafnar T,  Hunter DJ,  Chanock SJ,  Stefansson K,  Ioannidis JP,  Mann GJ,  Hopper JL,  Aitken JF,  Kefford RF,  Giles GG,  Armstrong BK,  Petersen GM,  Amundadottir L,  Fuchs CS,  Kraft P,  Stolzenberg-Solomon RZ,  Jacobs KB,  Arslan AA,  Bueno-de-Mesquita HB,  Gallinger S,  Gross M,  Helzlsouer K,  Holly EA,  Jacobs EJ,  Klein AP,  LaCroix A,  Li D,  Mandelson MT,  Olson SH,  Risch HA,  Zheng W,  Albanes D,  Bamlet WR,  Berg CD,  Boutron-Ruault MC,  Buring JE,  Bracci PM,  Canzian F,  Clipp S,  Cotterchio M,  de Andrade M,  Duell EJ,  Gaziano JM,  Giovannucci EL,  Goggins M,  Hallmans G,  Hankinson SE,  Hassan M,  Howard B,  Hunter DJ,  Hutchinson A,  Jenab M,  Kaaks R,  Kooperberg C,  Krogh V,  Kurtz RC,  Lynch SM,  McWilliams RR,  Mendelsohn JB,  Michaud DS,  Parikh H,  Patel AV,  Peeters PH,  Rajkovic A,  Riboli E,  Rodriguez L,  Seminara D,  Shu XO,  Thomas G,  Tjønneland A,  Tobias GS,  Trichopoulos D,  Van Den Eeden SK,  Virtamo J,  Wactawski-Wende J,  Wang Z,  Wolpin BM,  Yu H,  Yu K,  Zeleniuch-Jacquotte A,  Fraumeni JF Jr,  Hoover RN,  Hartge P,  Chanock SJ
Journal: PLoS One
Date: 2010
Branches: LTG, CGR
PubMed ID: 20526366
PMC ID: PMC2878330
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 (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. 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.