Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies.
<h4>Background</h4>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 eff...
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oai:doaj.org-article:ed86bff323304eb0bb405d306b6653682021-12-02T20:21:16ZEvaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies.1932-620310.1371/journal.pone.0010858https://doaj.org/article/ed86bff323304eb0bb405d306b6653682010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20526366/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Katherine S ElliottEleftheria ZegginiMark I McCarthyJulius GudmundssonPatrick SulemSimon N StaceySteinunn ThorlaciusLaufey AmundadottirHenrik GrönbergJianfeng XuValerie GaborieauRosalind A EelesDavid E NealJenny L DonovanFreddie C HamdyKenneth MuirShih-Jen HwangMargaret R SpitzBrent ZankeLuis Carvajal-CarmonaKevin M BrownAustralian Melanoma Family Study InvestigatorsNicholas K HaywardStuart MacgregorIan P M TomlinsonMathieu LemireChristopher I AmosJoanne M MurabitoWilliam B IsaacsDouglas F EastonPaul BrennanPanScan ConsortiumRosa B BarkardottirDaniel F GudbjartssonThorunn RafnarDavid J HunterStephen J ChanockKari StefanssonJohn P A IoannidisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 5, p e10858 (2010) |
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DOAJ |
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DOAJ |
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EN |
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Medicine R Science Q |
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Medicine R Science Q 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 PanScan Consortium Rosa B Barkardottir Daniel F Gudbjartsson Thorunn Rafnar David J Hunter Stephen J Chanock Kari Stefansson John P A Ioannidis Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. |
| description |
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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. |
| format |
article |
| author |
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 PanScan Consortium Rosa B Barkardottir Daniel F Gudbjartsson Thorunn Rafnar David J Hunter Stephen J Chanock Kari Stefansson John P A Ioannidis |
| author_facet |
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 PanScan Consortium Rosa B Barkardottir Daniel F Gudbjartsson Thorunn Rafnar David J Hunter Stephen J Chanock Kari Stefansson John P A Ioannidis |
| author_sort |
Katherine S Elliott |
| title |
Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. |
| title_short |
Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. |
| title_full |
Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. |
| title_fullStr |
Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. |
| title_full_unstemmed |
Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. |
| title_sort |
evaluation of association of hnf1b variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/ed86bff323304eb0bb405d306b665368 |
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