Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA.
British Journal of Cancer (Impact Factor: 4.82). 02/2008; 98(2):282-8. DOI: 10.1038/sj.bjc.6604170
Source: PubMed

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.

  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
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    ABSTRACT: Results conflict on the association between progesterone receptor gene (PRG) polymorphism PROGINS and ovarian cancer risk, despite wide-ranging investigations. We therefore performed a meta-analysis of 4,285 ovarian cancer cases and 6,257 controls from 11 published case-control studies. The strength of association between PROGINS polymorphism and ovarian cancer susceptibility was assessed using pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs). The results suggest no significant associations exist between PROGINS polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (T2T2 vs. T1T1: OR = 1.37, 95 % CI = 0.89-2.12, P = 0.15; T1T2 vs. T1T1:OR = 1.09, 95 % CI = 0.88-1.35, P = 0.41; T1T2 + T2T2 vs. T1T1:OR = 1.15, 95 % CI = 0.94-1.40, P = 0.17; T2T2 vs. T1 T1 + T1T2:OR = 1.34, 95 % CI = 0.87-2.07, P = 0.18). In conclusion, the results of this meta-analysis indicate that the PRG polymorphism PROGINS is not associated with ovarian cancer risk when multiple ethnic groups or regions were considered overall.
    Molecular Biology Reports 09/2013; 40(10). · 1.96 Impact Factor
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    ABSTRACT: Abstract Ovarian cancer is a highly lethal disease. Many researchers have, therefore, attempted to identify high risk populations. In this perspective, numerous genetic association studies have been performed to discover common ovarian cancer susceptibility variants. Accordingly, there is an increasing need to synthesize the evidence in order to identify true associations. A comprehensive and systematic assessment of all available data on genetic susceptibility to sporadic ovarian cancer was carried out. The evidence of statistically significant findings was evaluated based on the number of positive replications, the ratio of positive and negative studies, and the false-positive report probability (FPRP). The authors reviewed three genome-wide association studies (GWAS) and 147 candidate gene studies, published from 1990 to October 2010, including around 1100 genetic variants in more than 200 candidate genes and 20 intergenic regions. Genetic variants with the strongest evidence for an association with ovarian cancer include the rs2854344 in the RB1 gene and SNPs on chromosomes 9p22.2, 8q24, 2q31, and 19p13. Promising genetic pathways for ovarian cancer include the cell cycle, DNA repair, sex steroid hormone and oncogenic pathway. Concluding, this review shows that many genetic association studies have been performed, but only a few genetic variants show strong evidence for an association with ovarian cancer. More research is needed to elucidate causal genetic variants, taking into consideration gene–gene and gene–environment interactions, combined effects of common and rare variants, and differences between histological subtypes of this cancer.
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 12/2011; 1816(2):132. · 7.58 Impact Factor

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