Human Molecular Genetics Advance Access originally published online on March 20, 2009
Human Molecular Genetics 2009 18(12):2297-2304; doi:10.1093/hmg/ddp138
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Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study
1 CR-UK Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK 2 Gynaecological Oncology Unit, UCL EGA Institute for Women's Health, University College London, UK 3 Department of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark 4 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA 5 The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Australia 6 Keck School of Medicine, University of Southern California, Los Angeles, CA, USA 7 Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA 8 Gynaecologic Clinic, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 9 Department of Gynaecological and Obstetrics, Skejby University Hospital, Århus, Denmark 10 Program in Epidemiology, Fred Hutchinson Cancer Research Centre, Seattle, WA, USA 11 Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany 12 Department of Obstetrics and Gynaecology, University of Ulm, Ulm, Germany 13 Epidemiology Program, Cancer Research Centre of Hawaii, University of Hawaii, Honolulu, HI, USA 14 School of Public Health, The University of Texas, Houston, TX, USA 15 Roswell Park Cancer Centre, Buffalo, NY, USA 16 Mayo Clinic College of Medicine, Rochester, MN, USA 17 The Comprehensive Cancer Centre, Duke University Medical Centre, Durham, NC, USA 18 Department of Statistical Science, Duke University, Durham, NC, USA 19 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA 20 Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Institute of Oncology and Cancer Centre, Warsaw, Poland 21 Department of Epidemiology, University of California, Irvine, CA, USA 22 Department of OB/GYN, School of Medicine, University of North Carolina, Chapel Hill, CA NC27599-7570, USA 23 CR-UK Genetic Epidemiology Unit, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK
* To whom correspondence should be addressed. Tel: +44 1223740161; Fax: +44 1223740147; Email: honglin{at}srl.cam.ac.uk
Received January 13, 2009; Revised March 11, 2009; Accepted March 18, 2009
Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case–control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01–1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07–1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.