Genetic Variation in the Progesterone Receptor Gene and Ovarian Cancer Risk

Abstract

Evidence suggests a role for progesterone in ovarian cancer development. Progesterone exerts its effect on target cells by interacting with its receptor. Thus, genetic variations that may cause alterations in the biologic functions of the progesterone receptor can potentially contribute to individual susceptibility to ovarian cancer. Using a population-based, case-control study, the authors genotyped four polymorphisms in the progesterone receptor gene (+44C/T, +331G/A, G393G, V660L) and inferred haplotypes in 987 ovarian cancer cases and 1,034 controls living in New Hampshire and eastern Massachusetts (May 1992-November 2002). Odds ratios and 95% confidence intervals were calculated to evaluate associations with ovarian cancer. No associations were observed between the +44C/T, +331G/A, and G393G polymorphisms and ovarian cancer. However, an inverse association was observed between the V660L variant and ovarian cancer (odds ratio = 0.70, 95% confidence interval: 0.57, 0.85). Associations remained after adjustment for potential confounders. Five haplotypes occurred with greater than 5% frequency, and the haplotype carrying the V660L variant had a significant association with ovarian cancer (odds ratio = 0.76, 95% confidence interval: 0.62, 0.92). Associations were similar after stratifying by ovarian cancer histologies and risk factors.

Trinucleotide Repeat Polymorphisms in the Androgen Receptor Gene and Risk of Ovarian Cancer

“…The mean and median AR CAG lengths for both the CAG_S and CAG_L alleles in Caucasian subjects in the North Carolina Ovarian Cancer study population are similar to lengths reported in previous studies (20,21,27). No relationship was found between CAG repeat length and ovarian cancer among the Caucasians in this study.…”

“…Although we did not detect evidence for a threshold in CAG repeat length in Caucasians, we calculated the age-adjusted OR for a CAG_S repeat length <16 of 0.8 (95% CI, 0.4-1.5) and for the CAG_L repeat length <19 of 0.6 (95% CI, 0.3-1.2). We also conducted unconditional logistic regression analyses in Caucasian subjects using a cutoff point of z22 CAG repeats to compare our data to those of previously published reports (20,21,27). The age-adjusted ORs for the association between those who carry either one or two alleles with z22 CAG repeats versus those with two alleles with <22 repeats were 1.2 (95% CI, 0.9-1.6) and 1.2 (95% CI 0.8-1.7), respectively (see Table 6).…”

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

“…Included in this report are data from 16 OCAC studies. Ten of these are from the USA: the Diseases of the Ovary and their Evaluation (DOVE), the Genetic Epidemiology of Ovarian Cancer Study (GEOCS; previously FROCS) (Auranen et al, 2005;Song et al, 2006), the Hawaii Ovarian Cancer Study (HAWAII) (Goodman et al, 2001b), the Hormones and Ovarian Cancer Prediction Study (HOPE) (Pearce et al, 2008a), the Mayo Clinic Ovarian Cancer Case -Control Study (MAYO) (Sellers et al, 2005), the North Carolina Ovarian Cancer Study (NCOCS) (Berchuck et al, 2004), the New England-based Case -Control Study (Terry et al, 2005), the Ovarian Contraceptive and Reproductive Experiences study (Holt et al, 2007), the Orange and San Diego Counties, California (UCI) study and the USC/Los Angeles County Case -Control Studies of Ovarian Cancer (USC) (Pearce et al, 2008b). There are data from three European studies: the Danish Malignant Ovarian Cancer Study (MALOVA) (Auranen et al, 2005;Song et al, 2006), the UK SEARCH Ovarian Cancer Study (SEARCH) (Auranen et al, 2005;Song et al, 2006), and the UK Ovarian Population Study (UKOPS) (Ramus et al, 2008).…”

Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the ovarian cancer association consortium pooled analysis

“…The participating groups for this PGR study are the Australian Cancer Study, (Merritt et al, 2008) the Australian Ovarian Cancer Study (Merritt et al, 2008), the Connecticut Ovary Study (CONN) (Risch et al, 2006), the Family Registry for Ovarian Cancer Study (Auranen et al, 2005;Song et al, 2006), the Hormones and Ovarian Cancer Prediction Study, the Danish Malignant Ovarian Cancer Study (MALOVA) (Auranen et al, 2005;Song et al, 2006), the Mayo Clinic Ovarian Cancer Case -Control Study (Sellers et al, 2005), the North Carolina Ovarian Cancer Study (Berchuck et al, 2004), the New England-based Case -Control Study (NECC) (Terry et al, 2005), the Polish Ovarian Cancer Study (POCS) (García-Closas et al, 2007), the UK SEARCH Ovarian Cancer Study (SEARCH) (Auranen et al, 2005;Song et al, 2006) and the USC/Los Angeles County Case -Control Studies of Ovarian Cancer (USC) (Pearce et al, 2005). Details of these studies have been published previously (Gayther et al, 2007); Table 1 shows the basic information for each study.…”

“…The PROGINS (or variants in which it is in perfect linkage disequilibrium) has been studied by many groups in relation to ovarian cancer risk. The results are, however, equivocal Manolitsas et al, 1997;Lancaster et al, 1998Lancaster et al, , 2003Spurdle et al, 2001;Tong et al, 2001;Agoulnik et al, 2004;Pearce et al, 2005;Terry et al, 2005;Romano et al, 2006). Pearce et al (2005), suggested that a variant 3 0 of the PGR (rs608995), in partial linkage disequilibrium with the PROGINS, might be a better marker of ovarian cancer risk, but this has not been confirmed by other investigators.…”