title: Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis.
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.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA. cpearce@usc.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Pearce
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authors.lastname: Wu
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authors.lastname: Gayther
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authors.lastname: Garcia-Closas
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authors.initials: EL
authors.lastname: Goode
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authors.lastname: Lissowska
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authors.lastname: McGuire
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authors.forename: R B
authors.initials: RB
authors.lastname: Ness
authors.forename: S J
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authors.lastname: Ramus
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authors.forename: T A
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authors.forename: H
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authors.lastname: Song
authors.forename: D O
authors.initials: DO
authors.lastname: Stram
authors.forename: K L
authors.initials: KL
authors.lastname: Terry
authors.forename: P M
authors.initials: PM
authors.lastname: Webb
authors.forename: D C
authors.initials: DC
authors.lastname: Whiteman
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authors.initials: AS
authors.lastname: Whittemore
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: P D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: M C
authors.initials: MC
authors.lastname: Pike
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authors.initials: J
authors.lastname: Schildkraut
authors.forename: A
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authors.lastname: Berchuck
mesh_terms: D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors
chemical_list: D011980:Receptors, Progesterone