TY - JOUR
T1 - Evaluation of association of HNF1B variants with diverse cancers
T2 - Collaborative analysis of data from 19 genome-wide association studies
AU - Australian Melanoma Family Study Investigators
AU - The PanScan Consortium
AU - Elliott, Katherine S.
AU - Zeggini, Eleftheria
AU - McCarthy, Mark I.
AU - Gudmundsson, Julius
AU - Sulem, Patrick
AU - Stacey, Simon N.
AU - Thorlacius, Steinunn
AU - Amundadottir, Laufey
AU - Grönberg, Henrik
AU - Xu, Jianfeng
AU - Gaborieau, Valerie
AU - Eeles, Rosalind A.
AU - Neal, David E.
AU - Donovan, Jenny L.
AU - Hamdy, Freddie C.
AU - Muir, Kenneth
AU - Hwang, Shih Jen
AU - Spitz, Margaret R.
AU - Zanke, Brent
AU - Carvajal-Carmona, Luis
AU - Brown, Kevin M.
AU - Hayward, Nicholas K.
AU - Macgregor, Stuart
AU - Tomlinson, Ian P.M.
AU - Lemire, Mathieu
AU - Amos, Christopher I.
AU - Murabito, Joanne M.
AU - Isaacs, William B.
AU - Easton, Douglas F.
AU - Brennan, Paul
AU - Barkardottir, Rosa B.
AU - Gudbjartsson, Daniel F.
AU - Rafnar, Thorunn
AU - Hunter, David J.
AU - Chanock, Stephen J.
AU - Stefansson, Kari
AU - Ioannidis, John P.A.
AU - Mann, Graham J.
AU - Hopper, John L.
AU - Aitken, Joanne F.
AU - Kefford, Richard F.
AU - Giles, Graham G.
AU - Armstrong, Bruce K.
AU - Petersen, Gloria M.
AU - Fuchs, Charles S.
AU - Kraft, Peter
AU - Stolzenberg-Solomon, Rachael Z.
AU - Jacobs, Kevin B.
AU - Arslan, Alan A.
AU - Lynch, Shannon M.
PY - 2010/5/28
Y1 - 2010/5/28
N2 - 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.
AB - 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.
KW - Cooperative Behavior
KW - Databases, Genetic
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study/methods
KW - Hepatocyte Nuclear Factor 1-beta/genetics
KW - Humans
KW - Neoplasms/genetics
KW - Polymorphism, Single Nucleotide/genetics
UR - https://www.scopus.com/pages/publications/77956530101
U2 - 10.1371/journal.pone.0010858
DO - 10.1371/journal.pone.0010858
M3 - Article
C2 - 20526366
AN - SCOPUS:77956530101
SN - 1932-6203
VL - 5
SP - e10858
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e10858
ER -
