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

Journal article


Publication Details

Author(s): Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, Li Q, Marks JR, Berchuck A, Lee JM, Aben KKH, Anton-Culver H, Antonenkova N, Bandera EV, Bean Y, Beckmann M, Bisogna M, Bjorge L, Bogdanova N, Brinton LA, Brooks-Wilson A, Bruinsma F, Butzow R, Campbell IG, Carty K, Chang-Claude J, Chenevix-Trench G, Chen A, Chen Z, Cook LS, Cramer DW, Cunningham JM, Cybulski C, Plisiecka-Halasa J, Dennis J, Dicks E, Doherty JA, Doerk T, Du Bois A, Eccles D, Easton DT, Edwards RP, Eilber U, Ekici AB, Fasching P, Fridley BL, Gao YT, Gentry-Maharaj A, Giles GG, Glasspool R, Goode EL, Goodman MT, Gronwald J, Harter P, Hasmad HN, Hein A, Heitz F, Hildebrandt MAT, Hillemanns P, Hogdall E, Hogdall C, Hosono S, Jakubowska A, Paul J, Jensen A, Karlan BY, Kjaer SK, Kelemen LE, Kellar M, Kelley JL, Kiemeney LA, Krakstad C, Lambrechts D, Lambrechts S, Le ND, Lee AW, Cannioto R, Leminen A, Lester J, Levine DA, Liang D, Lissowska J, Lu K, Lubinski J, Lundvall L, Massuger LFAG, Matsuo K, Mcguire V, Mclaughlin JR, Nevanlinna H, Mcneish I, Menon U, Modugno F, Moysich KB, Narod SA, Nedergaard L, Ness RB, Azmi MAN, Odunsi K, Olson SH, Orlow I, Orsulic S, Pearce CL, Pejovic T, Pelttari LM, Permuth-Wey J, Phelan CM, Pike MC, Poole EM, Ramus SJ, Risch HA, Rosen B, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Rzepecka IK, Salvesen HB, Budzilowska A, Sellers TA, Shu XO, Shvetsov YB, Siddiqui N, Sieh W, Song H, Southey MC, Sucheston L, Tangen IL, Teo SH, Terry KL, Thompson PJ, Timorek A, Tworoger SS, Van Nieuwenhuysen E, Vergote I, Vierkant RA, Wang-Gohrke S, Walsh C, Wentzensen N, Whittemore AS, Wicklund KG, Wilkens LR, Woo YL, Wu X, Wu AH, Yang H, Zheng W, Ziogas A, Coetzee GA, Freedman ML, Monteiro ANA, Moes-Sosnowska J, Kupryjanczyk J, Pharoah PD, Gayther SA, Schildkraut JM
Journal: Carcinogenesis
Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B
Publication year: 2015
Volume: 36
Journal issue: 11
Pages range: 1341-53
ISSN: 0143-3334


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 genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.



FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hein, Alexander PD Dr.
Frauenklinik


External institutions with authors

Aichi Cancer Center Research Institute
Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cancer Council Victoria
Cancer Research Initiatives Foundation (CARIF)
Cedars-Sinai Medical Center
Danish Cancer Society
Danish Cancer Society Research Center
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fred Hutchinson Cancer Research Center
Friedrich-Schiller-Universität Jena
Glasgow Royal Infirmary (GRI)
Harvard University
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
H. Lee Moffitt Cancer Center & Research Institute
Kliniken Essen-Mitte
Kyushu University / 九州大学
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medical University of South Carolina (MUSC)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Memorial Sloan Kettering Cancer Center
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Princess Anne Hospital
Princess Margaret Cancer Centre / Princess Margaret Hospital
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Shanghai Cancer Institute / 上海市肿瘤研究所
Stanford University
Texas Southern University (TSU)
The University of Melbourne
Universität Ulm
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Copenhagen
University of Florida
University of Glasgow
University of Hawaii (U.H.)
University of Kansas (KU)
University of Malaya (UM) / Universiti Malaya
University of Michigan
University of New Mexico
University of Pittsburgh
University of Southern California (USC)
University of Texas MD Anderson Cancer Center
University of Washington
Vanderbilt University
Women's College Hospital
Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu
Xiamen University


How to cite

APA:
Lawrenson, K., Iversen, E.S., Tyrer, J., Weber, R.P., Concannon, P., Hazelett, D.J.,... Schildkraut, J.M. (2015). Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer. Carcinogenesis, 36(11), 1341-53. https://dx.doi.org/10.1093/carcin/bgv138

MLA:
Lawrenson, Kate, et al. "Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer." Carcinogenesis 36.11 (2015): 1341-53.

BibTeX: 

Last updated on 2019-21-07 at 08:03