1. ¹Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Room 4415A, Los Angeles, CA 90089, USA
2. ²Translational Research Laboratories, Windeyer Institute, University College London, 46 Cleveland Street, London W1T 4JF, UK
3. ³Department of Genetics, Yale University School of Medicine, 333 Cedar Street, SHM I-321, New Haven, CT 06510, USA
4. ⁴The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Herston, Brisbane QLD 4029, Australia
5. ⁵Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 4605, 8717 Grovemont Circle, Gaithersburg, MD 20892-4605, USA
6. ⁶Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, 221 Longwood, Boston, MA 02115, USA
7. ⁷Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
8. ⁸Magee-Womens Research Institute, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA 15213, USA
9. ⁹Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
10. ¹⁰Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard, Room 5014, Rockville, MD 20852-7234, USA
11. ¹¹Department of Virus, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Rigshospitalet Strandboulevarden 49, Copenhagen DK-2100, Denmark
12. ¹²Department of Cancer Epidemiology and Prevention, Cancer Center and M Sklodowska-Curie Institute of Oncology, Roentgena 5, Warszawa 02-781, Poland
13. ¹³Division of Epidemiology and Biostatistics, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA
14. ¹⁴Department of Epidemiology and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
15. ¹⁵Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, PO Box 208034, New Haven, CT 06520-8034, USA
16. ¹⁶Division of Cancer Prevention & Control, H Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
17. ¹⁷CR-UK Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK
18. ¹⁸Department of Pathology, University of Arizona Medical College, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
19. ¹⁹Division of Preventive Medicine, The Duke Comprehensive Cancer Center, Durham, NC 27710, USA

Correspondence: Dr CL Pearce, E-mail: cpearce@usc.edu

Received 24 September 2007; Revised 20 November 2007; Accepted 27 November 2007; Published online 22 January 2008.

Abstract

There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case–control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3' variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case–control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01–1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62–1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.