Journal article

Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

Kate Lawrenson, Edwin S Iversen, Jonathan Tyrer, Rachel Palmieri Weber, Patrick Concannon, Dennis J Hazelett, Qiyuan Li, Jeffrey R Marks, Andrew Berchuck, Janet M Lee, Katja KH Aben, Hoda Anton-Culver, Natalia Antonenkova, Elisa V Bandera, Yukie Bean, Matthias W Beckmann, Maria Bisogna, Line Bjorge, Natalia Bogdanova, Louise A Brinton Show all

Carcinogenesis | OXFORD UNIV PRESS | Published : 2015

Abstract

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of g..

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Grants

Awarded by Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative


Awarded by COGS project through a European Commission's Seventh Framework Programme grant


Awarded by Ovarian Cancer Research Fund


Awarded by Department of Defense Award


Awarded by National Institutes of Health


Awarded by Department of Defense


Awarded by California Cancer Research Program


Awarded by Lon V Smith Foundation


Awarded by National Center for Research Resources/General Clinical Research Center


Awarded by US Public Health Service


Awarded by National Cancer Institute


Awarded by National Center for Advancing Translational Sciences (NCATS)


Awarded by National Center for Research Resources / General Clinical Research Center


Awarded by DIVISION OF CANCER CONTROL &POPULATION SCIENCE


Awarded by DIVISION OF CANCER PREVENTION AND CONTROL


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES


Awarded by Cancer Research UK


Awarded by The Francis Crick Institute


Awarded by National Breast Cancer Foundation


Funding Acknowledgements

The scientific development and funding for this project were supported by the following: the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112); the COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175-HEALTH-F2-2009-223175); the Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07); and Department of Defense Award (W81XWH-12-1-0561, W81XWH-07-0449). F.M. was supported by National Institutes of Health K07-CA080668; S.S.T. and E.M.P. were supported in part by Department of Defense Award W81XWH-12-1-0561. Funding of the constituent studies was provided by: California Cancer Research Program (00-01389V-20170, 2II0200); Cancer Prevention Institute of California; Department of Defense (DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-10-1-02802); Fred C. and Katherine B. Andersen Foundation; Lon V Smith Foundation grant LVS-39420; Mayo Foundation; Minnesota Ovarian Cancer Alliance; National Institutes of Health (K07-CA095666, K07-CA143047, K22-CA138563); National Center for Research Resources/General Clinical Research Center grant M01-RR000056, N01-CN025403, N01-CN55424, N01-PC67001, N01-PC67010, P01-CA17054, P30-CA14089, P30-CA15083, P30-CA072720, P50-CA105009, P50-CA136393, P50-CA159981, R01-CA058860, R01-CA074850, R01-CA080742, R01-CA092044, R01-CA112523, R01-CA122443, R01-CA126841, R01-CA16056, R01-CA54419, R01-CA58598, R01-CA61132, R01-CA76016, R01-CA83918, R01-CA87538, R01-CA95023, R01-CA063678, R01 CA114343, R03-CA113148, R03-CA115195, U01-CA69417, U01-CA71966), UM1-CA182910; Rutgers Cancer Institute of New Jersey; and the US Public Health Service (PSA-042205). Personal support: K.L is supported by a K99/R00 grant from the National Cancer Institute (Grant number 1K99CA184415-01). D.F.E. is a Principal Research Fellow of Cancer Research UK. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. B.K. holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.