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Genome-wide association study identifies a common variant associated with risk of endometrial cancer


Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10−10) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.

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Figure 1: Forest plot showing the association between rs4430796 and endometrial cancer for each component of the study.


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This work was supported by the National Health and Medical Research Council (NHMRC; ID 552402), the Wellcome Trust and by Cancer Research UK grants C1287/A10118, C490/A1021, C8197/A10865 and C8197/A10123. A.B.S. and P.M.W. are NHMRC Senior Research Fellows, and G.M. is an NHMRC Senior Principle Research Fellow. T.O. is supported by an Australian Postgraduate Award, an Institute of Health and Biomedical Innovation PhD Top-Up and a Smart State PhD Award. L.C.W. is a John Gavin Postdoctoral Fellow (Genesis Oncology Trust, New Zealand). D.F.E. is a Principal Research Fellow of Cancer Research UK. A.M.D. is supported by the Joseph Mitchell Trust. I.T. is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. P.A.F. was partly funded by the Dr. Mildred Scheel Stiftung of the Deutsche Krebshilfe (German Cancer Aid).

This study makes use of data generated by the Wellcome Trust Case Control Consortium (WTCCC) 2. A full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. Funding for this project was provided by the Wellcome Trust under award 085475.

We thank the study participants and collaborators and the research teams involved in the design and implementation of the individual studies included (see Supplementary Note for full list of collaborators and specific acknowledgments). Australian National Endometrial Cancer Study (ANECS) recruitment was supported by project grants from the National Health and Medical Research Council of Australia (ID#339435), The Cancer Council Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and ID#457636). The Bavarian Endometrial Cancer Study (BECS) was partly funded by the Erlanger Leistungsbezogene Anschubfinanzierung und Nachwuchsförderung Fond (ELAN fund) of the University of Erlangen. The Leuven Endometrium Study (LES) was supported by the Verelst Foundation for endometrial cancer. Molecular Markers in Treatment of Endometrial Cancer (MoMaTEC) received financial support from a Helse Vest Grant, the University of Bergen, Melzer Foundation, the Norwegian Cancer Society (Harald Andersens legat), the Research Council of Norway and Haukeland University Hospital. The Newcastle Endometrial Cancer Study (NECS) acknowledges contributions from the University of Newcastle, the National Broadcasting Network (NBN) Children's Cancer Research Group, Jennie Thomas and the Hunter Medical Research Institute. The National Study of Endometrial Cancer Genetics (NSECG) Group was supported principally by Cancer Research UK and by funds from the Oxford Comprehensive Biomedical Research Centre, with core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford provided by grant 075491/Z/04. The Polish Endometrial Cancer Study (PECS) was funded by the intramural research program at the US National Cancer Institute, Division of Cancer Epidemiology and Genetics in the Hormonal and Reproductive Epidemiology Branch. The Singapore and Swedish Breast/Endometrial Cancer Study (SASBAC) was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institutes of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The Shanghai Endometrial Cancer Genetic Study (SECGS) was supported by grants from the National Cancer Institute of the United States Public Health Service (RO1 CA 092585 and R01 CA90899, R01 CA64277). SEARCH is funded by a program grant from Cancer Research UK (C490/A10124).

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Authors and Affiliations




A.B.S., D.F.E., G.M. and P.M.W. obtained funding for the study. A.B.S. and D.F.E. designed the study. A.B.S. and D.J.T. drafted the manuscript. P.F. and K.M. conducted preliminary analysis, and D.F.E. and D.J.T. conducted the final statistical analyses. A.B.S. and P.M.W. coordinated the ANECS. P.D.P. and D.F.E. coordinated Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH). A.B.S., K.F. and T.O. coordinated the ANECS stage 1 genotyping. A.M.D., S.A. and C.S.H. coordinated the SEARCH stage 1 genotyping. L.C.W., S.B.M. and E.T.D. conducted analyses to assess correlations between genotype and gene expression. J.M. provided data management and bioinformatics support. T.O. and K.F. coordinated the ANECS and other Brisbane-based stage 2 genotyping and assisted with data management. S.A., C.S.H. and A.M.D. coordinated the stage 2 genotyping of the SEARCH samples. M.S. coordinated overall management of data for SEARCH samples. D.L., P.H., K.C., J. Liu, J. Li, I.T., K.H., M.G.-C., N.W., H.Y., S.C., X.-O.S. and J. Long coordinated the stage 2 genotyping, or extraction of existing genotype data, for the LES, SASBAC, NSECG, PECS and SECGS samples. The following authors coordinated the baseline studies and/or extraction of questionnaire and clinical information for studies included in stage 2 analysis: BECS (P.A.F., M.W.B., A.H. and A.B.E.); LES (D.L., L.C., I.V. and F.A.); MoMaTEC (H.B.S., J.T., H.H. and T.S.N.); NECS (R.J.S., K.A., T.P. and G.O.); NSECG (I.T., K.H., M.G. and S.H.); PECS (M.G.-C., H.Y. and N.W.); SASBAC (P.H., K.C., and J. Li); SECGS (X.-O.S. and W.Z. (principal investigators), J. Long (principal study geneticist) and Y.-B.X. (site principal investigator at the Shanghai Cancer Institute)). All authors provided critical review of the manuscript.

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Correspondence to Amanda B Spurdle.

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A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

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Supplementary Note, Supplementary Figures 1 and 2 and Supplementary Tables 1–7. (PDF 232 kb)

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Spurdle, A., Thompson, D., Ahmed, S. et al. Genome-wide association study identifies a common variant associated with risk of endometrial cancer. Nat Genet 43, 451–454 (2011).

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