Evaluation of Association of HNF1B Variants with Diverse Cancers: Collaborative Analysis of Data from 19 Genome-Wide Association Studies

被引：28

作者：

Elliott, Katherine S. ^{[1
]}

Zeggini, Eleftheria ^{[1
,2
]}

McCarthy, Mark I. ^{[1
,3
]}

Gudmundsson, Julius ^{[4
]}

Sulem, Patrick ^{[4
]}

Stacey, Simon N. ^{[4
]}

Thorlacius, Steinunn ^{[4
]}

Amundadottir, Laufey ^{[5
]}

Groenberg, Henrik ^{[6
]}

Xu, Jianfeng ^{[7
,8
]}

Gaborieau, Valerie ^{[9
]}

Eeles, Rosalind A. ^{[10
]}

Neal, David E. ^{[11
]}

Donovan, Jenny L. ^{[12
]}

Hamdy, Freddie C. ^{[13
]}

Muir, Kenneth ^{[14
]}

Hwang, Shih-Jen ^{[15
]}

Spitz, Margaret R. ^{[16
]}

Zanke, Brent ^{[17
,18
]}

Carvajal-Carmona, Luis ^{[1
]}

Brown, Kevin M. ^{[19
]}

Hayward, Nicholas K. ^{[20
]}

Macgregor, Stuart ^{[20
]}

Tomlinson, Ian P. M. ^{[1
]}

Lemire, Mathieu ^{[17
]}

Amos, Christopher I. ^{[16
]}

Murabito, Joanne M. ^{[21
]}

Isaacs, William B. ^{[22
]}

Easton, Douglas F. ^{[23
]}

Brennan, Paul

Barkardottir, Rosa B. ^{[24
,25
]}

Gudbjartsson, Daniel F. ^{[4
]}

Rafnar, Thorunn ^{[4
]}

Hunter, David J. ^{[26
]}

Chanock, Stephen J. ^{[5
]}

Stefansson, Kari ^{[4
]}

Ioannidis, John P. A. ^{[27
,28
,29
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[2] Univ Cambridge, Wellcome Trust Sanger Inst, Cambridge, England

[3] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[4] deCODE Genet, Reykjavik, Iceland

[5] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[6] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[7] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA

[8] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA

[9] IARC, Genet Epidemiol Grp, Lyon, France

[10] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England

[11] Univ Cambridge, Dept Oncol, Cambridge, England

[12] Univ Bristol, Dept Social Med, Bristol, Avon, England

[13] Univ Oxford, Nuffield Dept Surg, Oxford, England

[14] Univ Warwick, Hlth Sci Res Inst, Coventry CV4 7AL, W Midlands, England

[15] NHLBI, Framingham Study, Bethesda, MD 20892 USA

[16] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[17] Ontario Inst Canc Res, MaRS Ctr, Toronto, ON, Canada

[18] Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON, Canada

[19] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ USA

[20] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia

[21] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA

[22] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA

[23] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Cambridge, England

[24] Landspitali Univ Hosp Iceland, Dept Pathol, Reykjavik, Iceland

[25] Univ Iceland, Fac Med, Reykjavik, Iceland

[26] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[27] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece

[28] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece

[29] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modelling, Boston, MA 02111 USA

来源：

PLOS ONE | 2010年 / 5卷 / 05期

基金：

美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 瑞典研究理事会; 英国惠康基金;

关键词：

PROSTATE-CANCER; DIABETES-MELLITUS; SUSCEPTIBILITY LOCUS; LUNG-CANCER; RISK LOCI; SEQUENCE VARIANTS; GENE; METAANALYSIS; REPLICATION; SCAN;

D O I：

10.1371/journal.pone.0010858

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

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