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Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.

Publication ,  Journal Article
Berchuck, A; Schildkraut, JM; Wenham, RM; Calingaert, B; Ali, S; Henriott, A; Halabi, S; Rodriguez, GC; Gertig, D; Purdie, DM; Kelemen, L ...
Published in: Cancer Epidemiol Biomarkers Prev
December 2004

OBJECTIVE: The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of the A and B isoforms and has been associated with an increased risk of endometrial and breast cancer. In this study, we sought to determine whether this polymorphism affects ovarian cancer risk. METHODS: The +331G/A polymorphism was genotyped in a population-based, case-control study from North Carolina that included 942 Caucasian subjects (438 cases, 504 controls) and in a confirmatory group from Australia (535 cases, 298 controls). Logistic regression analysis was used to calculate age-adjusted odds ratios (OR). RESULTS: There was a suggestion of a protective effect of the +331A allele (AA or GA) against ovarian cancer in the North Carolina study [OR, 0.72; 95% confidence interval (95% CI), 0.47-1.10]. Examination of genotype frequencies by histologic type revealed that this was due to a decreased risk of endometrioid and clear cell cancers (OR, 0.30; 95% CI, 0.09-0.97). Similarly, in the Australian study, there was a nonsignificant decrease in the risk of ovarian cancer among those with the +331A allele (OR, 0.83; 95% CI, 0.51-1.35) that was strongest in the endometrioid/clear cell group (OR, 0.60; 95% CI, 0.24-1.44). In the combined U.S.-Australian data that included 174 endometrioid/clear cell cases (166 invasive, 8 borderline), the +331A allele was significantly associated with protection against this subset of ovarian cancers (OR, 0.46; 95% CI, 0.23-0.92). Preliminary evidence of a protective effect of the +331A allele against endometriosis was also noted in control subjects (OR, 0.19; 95% CI, 0.03-1.38). CONCLUSIONS: These findings suggest that the +331G/A progesterone receptor promoter polymorphism may modify the molecular epidemiologic pathway that encompasses both the development of endometriosis and its subsequent transformation into endometrioid/clear cell ovarian cancer.

Duke Scholars

Published In

Cancer Epidemiol Biomarkers Prev

ISSN

1055-9965

Publication Date

December 2004

Volume

13

Issue

12

Start / End Page

2141 / 2147

Location

United States

Related Subject Headings

  • Risk Factors
  • Receptors, Progesterone
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Ovarian Neoplasms
  • Odds Ratio
  • Middle Aged
  • Humans
  • Female
  • Epidemiology
 

Citation

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MLA
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Berchuck, A., Schildkraut, J. M., Wenham, R. M., Calingaert, B., Ali, S., Henriott, A., … Chenevix-Trench, G. (2004). Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers. Cancer Epidemiol Biomarkers Prev, 13(12), 2141–2147.
Berchuck, Andrew, Joellen M. Schildkraut, Robert M. Wenham, Brian Calingaert, Shazia Ali, Amy Henriott, Susan Halabi, et al. “Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.Cancer Epidemiol Biomarkers Prev 13, no. 12 (December 2004): 2141–47.
Berchuck A, Schildkraut JM, Wenham RM, Calingaert B, Ali S, Henriott A, et al. Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers. Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):2141–7.
Berchuck, Andrew, et al. “Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.Cancer Epidemiol Biomarkers Prev, vol. 13, no. 12, Dec. 2004, pp. 2141–47.
Berchuck A, Schildkraut JM, Wenham RM, Calingaert B, Ali S, Henriott A, Halabi S, Rodriguez GC, Gertig D, Purdie DM, Kelemen L, Spurdle AB, Marks J, Chenevix-Trench G. Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers. Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):2141–2147.

Published In

Cancer Epidemiol Biomarkers Prev

ISSN

1055-9965

Publication Date

December 2004

Volume

13

Issue

12

Start / End Page

2141 / 2147

Location

United States

Related Subject Headings

  • Risk Factors
  • Receptors, Progesterone
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Ovarian Neoplasms
  • Odds Ratio
  • Middle Aged
  • Humans
  • Female
  • Epidemiology