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

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-CarmonaKevin M. Brown, 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, Rosa B. Barkardottir, Daniel F. Gudbjartsson, Thorunn Rafnar, David J. Hunter, Stephen J. Chanock, Kari Stefansson, John P A Ioannidis

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere10858
JournalPLoS One
Volume5
Issue number5
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Genome-Wide Association Study
prostatic neoplasms
data analysis
Genes
Prostatic Neoplasms
neoplasms
Neoplasms
alleles
Alleles
odds ratio
confidence interval
Medical problems
Odds Ratio
pancreatic neoplasms
Confidence Intervals
HapMap Project
genome-wide association study
lung neoplasms
melanoma
linkage disequilibrium

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Elliott, K. S., Zeggini, E., Mccarthy, M. I., Gudmundsson, J., Sulem, P., Stacey, S. N., ... Ioannidis, J. P. A. (2010). Evaluation of association of HNF1B variants with diverse cancers: Collaborative analysis of data from 19 genome-wide association studies. PLoS One, 5(5), [e10858]. https://doi.org/10.1371/journal.pone.0010858

Evaluation of association of HNF1B variants with diverse cancers : Collaborative analysis of data from 19 genome-wide association studies. / 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.; Hayward, Nicholas K.; Macgregor, Stuart; Tomlinson, Ian P M; Lemire, Mathieu; Amos, Christopher I.; Murabito, Joanne M.; Isaacs, William B.; Easton, Douglas F.; Brennan, Paul; Barkardottir, Rosa B.; Gudbjartsson, Daniel F.; Rafnar, Thorunn; Hunter, David J.; Chanock, Stephen J.; Stefansson, Kari; Ioannidis, John P A.

In: PLoS One, Vol. 5, No. 5, e10858, 2010.

Research output: Contribution to journalArticle

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, Hayward, NK, Macgregor, S, Tomlinson, IPM, Lemire, M, Amos, CI, Murabito, JM, Isaacs, WB, Easton, DF, Brennan, P, Barkardottir, RB, Gudbjartsson, DF, Rafnar, T, Hunter, DJ, Chanock, SJ, Stefansson, K & Ioannidis, JPA 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. https://doi.org/10.1371/journal.pone.0010858
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. ; Hayward, Nicholas K. ; Macgregor, Stuart ; Tomlinson, Ian P M ; Lemire, Mathieu ; Amos, Christopher I. ; Murabito, Joanne M. ; Isaacs, William B. ; Easton, Douglas F. ; Brennan, Paul ; Barkardottir, Rosa B. ; Gudbjartsson, Daniel F. ; Rafnar, Thorunn ; Hunter, David J. ; Chanock, Stephen J. ; Stefansson, Kari ; Ioannidis, John P A. / Evaluation of association of HNF1B variants with diverse cancers : Collaborative analysis of data from 19 genome-wide association studies. In: PLoS One. 2010 ; Vol. 5, No. 5.
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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.",
author = "Elliott, {Katherine S.} and Eleftheria Zeggini and Mccarthy, {Mark I.} and Julius Gudmundsson and Patrick Sulem and Stacey, {Simon N.} and Steinunn Thorlacius and Laufey Amundadottir and Henrik Gr{\"o}nberg and Jianfeng Xu and Valerie Gaborieau and Eeles, {Rosalind A.} and Neal, {David E.} and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Kenneth Muir and Hwang, {Shih Jen} and Spitz, {Margaret R.} and Brent Zanke and Luis Carvajal-Carmona and Brown, {Kevin M.} and Hayward, {Nicholas K.} and Stuart Macgregor and Tomlinson, {Ian P M} and Mathieu Lemire and Amos, {Christopher I.} and Murabito, {Joanne M.} and Isaacs, {William B.} and Easton, {Douglas F.} and Paul Brennan and Barkardottir, {Rosa B.} and Gudbjartsson, {Daniel F.} and Thorunn Rafnar and Hunter, {David J.} and Chanock, {Stephen J.} and Kari Stefansson and Ioannidis, {John P A}",
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T1 - Evaluation of association of HNF1B variants with diverse cancers

T2 - Collaborative analysis of data from 19 genome-wide association studies

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

PY - 2010

Y1 - 2010

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.

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