steroids 73 ( 2 0 0 8 ) 676–680 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/steroids Progesterone receptor (PROGINS) polymorphism and the risk of ovarian cancer Daniela B. Leite * , Michele G. Junqueira, Cristina V. de Carvalho, Ana M. Massad-Costa, Wagner J. Gonc ¸alves, Sergio M. Nicolau, Luiz A.F. Lopes, Edmundo C. Baracat, Ismael D.C.G. da Silva Molecular Gynecology Laboratory, Department of Gynecology, Federal University of S˜ ao Paulo (UNIFESP-EPM), Brazil article info Article history: Received 8 October 2007 Received in revised form 12 February 2008 Accepted 15 February 2008 Published on line 23 February 2008 Keywords: Ovarian cancer Polymorphism PROGINS abstract The present case–control study evaluates the role of the progesterone receptor (PR) polymor- phism known as PROGINS as a risk factor for ovarian cancer development and investigates the association between these genetic variants and clinical/pathologic variables of ovarian cancer. PROGINS polymorphism was examined, by polymerase chain reaction, in a total of 80 patients with ovarian cancer and 282 control subjects. The frequencies of PROGINS polymor- phism T1/T1, T1/T2, and T2/T2 were 71.3, 15.0 and 13.8% in ovarian cancer patients and 78.37, 21.63 and 0% in controls, respectively. The  2 -test showed a higher incidence of the T2/T2 genotype (P =0.001) in the ovarian cancer group. In addition, women carrying a mutated allele (T2) showed approximately 2.2 times higher risk of ovarian cancer development as compared to women who have a variant allele (odds ratio (OR) = 2.2; 95% CI = 1.80–3.54). Regarding the clinical and pathologic findings observed within the cancer group, there was a significant correlation between PROGINS polymorphism and patients with a familial history ( 2 = 6.776; P = 0.009; Fischer exact test, P = 0.01). In this regard, patients with famil- ial antecedents have a 4.7 times higher likelihood to have at least one risk allele (T2) as compared with patients without familial antecedents (OR = 4.69; 95% CI = 1.38–15.87). No cor- relations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of ovarian cancer. © 2008 Elsevier Inc. All rights reserved. 1. Introduction Ovarian cancer is the sixth most common cancer worldwide and the seventh leading cause of death from cancer in women. Recent annual worldwide figures reflect 204,000 new cases of ovarian cancer and 125,000 deaths [1]. Moreover, the lifetime risk in ovarian cancer for women in industrialized countries is ∼2% [2]. Epithelial tumors account for 80–90% of ovarian malignancies in the United States and Western Europe [3]. ∗ Corresponding author at: Molecular Gynecology Laboratory, Rua Pedro de Toledo, 4th Floor, 04039-032 S˜ ao Paulo, SP, Brazil. Tel.: +55 11 55791534. E-mail address: dani.gineco@epm.br (D.B. Leite). Genetic and hormonal factors are known to influence the development and clinical course of ovarian cancer. Germline mutations in so-called high-penetrance cancer susceptible genes, such as BRCA1 and BRCA2, have been shown to account for only up to 5% of all ovarian and breast cancer cases. Therefore, relatively more common genes acting together with endogenous/lifestyle risk factors (low-penetrance genes) are likely to account for a much higher proportion of cancer cases together with yet unidentified high-penetrance genes [4]. 0039-128X/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.steroids.2008.02.005