Genetic Variation in the Progesterone Receptor Gene and Ovarian Cancer Risk

Overview

Journal Am J Epidemiol

Publisher Oxford University Press

Specialty Public Health

Date 2005 Feb 19

PMID 15718480

Citations 34

Authors

Kathryn L Terry

Immaculata De Vivo

Linda Titus-Ernstoff

Patrick M Sluss

Daniel W Cramer

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Rocereto T, Saul H, Aikins Jr J, Paulson J . Phase II study of mifepristone (RU486) in refractory ovarian cancer. Gynecol Oncol. 2000; 77(3):429-32. DOI: 10.1006/gyno.2000.5789. View

Berchuck A, Schildkraut J, Wenham R, Calingaert B, Ali S, Henriott A . Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers. Cancer Epidemiol Biomarkers Prev. 2004; 13(12):2141-7. View

Purdie D, Siskind V, Bain C, Webb P, Green A . Reproduction-related risk factors for mucinous and nonmucinous epithelial ovarian cancer. Am J Epidemiol. 2001; 153(9):860-4. DOI: 10.1093/aje/153.9.860. View

Spurdle A, Webb P, Purdie D, Chen X, Green A, Chenevix-Trench G . No significant association between progesterone receptor exon 4 Val660Leu G/T polymorphism and risk of ovarian cancer. Carcinogenesis. 2001; 22(5):717-21. DOI: 10.1093/carcin/22.5.717. View

Ivarsson K, Sundfeldt K, Brannstrom M, Janson P . Production of steroids by human ovarian surface epithelial cells in culture: possible role of progesterone as growth inhibitor. Gynecol Oncol. 2001; 82(1):116-21. DOI: 10.1006/gyno.2001.6219. View

Keith Bechtel M, Bonavida B . Inhibitory effects of 17beta-estradiol and progesterone on ovarian carcinoma cell proliferation: a potential role for inducible nitric oxide synthase. Gynecol Oncol. 2001; 82(1):127-38. DOI: 10.1006/gyno.2001.6221. View

Tong D, Fabjani G, Heinze G, Obermair A, Leodolter S, Zeillinger R . Analysis of the human progesterone receptor gene polymorphism progins in Austrian ovarian carcinoma patients. Int J Cancer. 2001; 95(6):394-7. DOI: 10.1002/1097-0215(20011120)95:6<394::aid-ijc1070>3.0.co;2-x. View

Runnebaum I, Wang-Gohrke S, Vesprini D, Kreienberg R, Lynch H, Moslehi R . Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. Pharmacogenetics. 2001; 11(7):635-8. DOI: 10.1097/00008571-200110000-00010. View

Schildkraut J, Calingaert B, Marchbanks P, Moorman P, Rodriguez G . Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk. J Natl Cancer Inst. 2002; 94(1):32-8. DOI: 10.1093/jnci/94.1.32. View

10.

Rodriguez G, Nagarsheth N, Lee K, Bentley R, Walmer D, Cline M . Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta. J Natl Cancer Inst. 2002; 94(1):50-60. DOI: 10.1093/jnci/94.1.50. View

11.

Zaykin D, Westfall P, Young S, Karnoub M, Wagner M, Ehm M . Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals. Hum Hered. 2002; 53(2):79-91. DOI: 10.1159/000057986. View

12.

De Vivo I, Huggins G, Hankinson S, Lescault P, Boezen M, Colditz G . A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk. Proc Natl Acad Sci U S A. 2002; 99(19):12263-8. PMC: 129433. DOI: 10.1073/pnas.192172299. View

13.

Hapangama D, Critchley H, Henderson T, Baird D . Mifepristone-induced vaginal bleeding is associated with increased immunostaining for cyclooxygenase-2 and decrease in prostaglandin dehydrogenase in luteal phase endometrium. J Clin Endocrinol Metab. 2002; 87(11):5229-34. DOI: 10.1210/jc.2002-020429. View

14.

Zhang K, Calabrese P, Nordborg M, Sun F . Haplotype block structure and its applications to association studies: power and study designs. Am J Hum Genet. 2002; 71(6):1386-94. PMC: 378580. DOI: 10.1086/344780. View

15.

Lancaster J, Wenham R, Halabi S, Calingaert B, Marks J, Moorman P . No relationship between ovarian cancer risk and progesterone receptor gene polymorphism in a population-based, case-control study in North Carolina. Cancer Epidemiol Biomarkers Prev. 2003; 12(3):226-7. View

16.

Li Q, Li J, Zhao X, Ji M . [Study of effect of mifepristone on apoptosis of human ovarian cancer cell line 3AO]. Zhonghua Fu Chan Ke Za Zhi. 2004; 38(10):625-8. View

17.

Cloven N, Kyshtoobayeva A, Burger R, Yu I, Fruehauf J . In vitro chemoresistance and biomarker profiles are unique for histologic subtypes of epithelial ovarian cancer. Gynecol Oncol. 2004; 92(1):160-6. DOI: 10.1016/j.ygyno.2003.09.030. View

18.

Dobson A, Conneely O, Beattie W, Maxwell B, Mak P, Tsai M . Mutational analysis of the chicken progesterone receptor. J Biol Chem. 1989; 264(7):4207-11. View

19.

Vegeto E, Allan G, Schrader W, Tsai M, McDonnell D, OMalley B . The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Cell. 1992; 69(4):703-13. DOI: 10.1016/0092-8674(92)90234-4. View

20.

Whittemore A, Harris R, Itnyre J . Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol. 1992; 136(10):1184-203. DOI: 10.1093/oxfordjournals.aje.a116427. View