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American Journal of Epidemiology 2005 161(5):442-451; doi:10.1093/aje/kwi064
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Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health

ORIGINAL CONTRIBUTIONS

Genetic Variation in the Progesterone Receptor Gene and Ovarian Cancer Risk

Kathryn L. Terry1,2 , Immaculata De Vivo2,3, Linda Titus-Ernstoff4, Patrick M. Sluss5 and Daniel W. Cramer1

1 Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
2 Department of Epidemiology, Harvard School of Public Health, Boston, MA.
3 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA.
4 Norris Cotton Cancer Center and the Departments of Community and Family Medicine and of Medicine, Dartmouth Medical School, Lebanon, NH.
5 Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.

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.

haplotypes; ovarian neoplasms; polymorphism, single nucleotide; receptors, progesterone

Abbreviations: CI, confidence interval; OR, odds ratio; rs, reference single nucleotide polymorphism; SNP, single nucleotide polymorphism.

Correspondence to Kathryn L. Terry, Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115 (e-mail: kterry{at}hsph.harvard.edu).


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