Journal Article

Ovarian Cancer and Polymorphisms in the Androgen and Progesterone Receptor Genes: A HuGE Review

Francesmary Modugno

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 159, issue 4, pages 319-335
Published in print February 2004 | ISSN: 0002-9262
Published online February 2004 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwh046
Ovarian Cancer and Polymorphisms in the Androgen and Progesterone Receptor Genes: A HuGE Review

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Ovarian cancer is the second most common gynecologic cancer among women and the second leading cause of death from gynecologic malignancy worldwide. Androgens, acting through androgen receptors (ARs), have been implicated in the disease, while progestins, acting through progesterone receptors (PGRs), may provide protection against the disease. The PGR gene contains several polymorphisms in the hormone-binding domain, three of which are in linkage disequilibrium (a complex referred to as PROGINS). PROGINS has been associated with increased risk of ovarian cancer. This association has not been found consistently, and it may be limited to women who do not use oral contraceptives. The AR gene contains a trinucleotide CAG repeat, the length of which has been inversely associated with the ability of the AR-ligand complex to transactivate androgen-responsive genes. Data on the association between the AR repeat length and ovarian cancer, both in general and among carriers of mutations in the breast cancer 1 and 2 (BRCA1/2) genes, are inconclusive. There is insufficient evidence that polymorphisms in either the PGR gene or the AR gene may be a risk factor for ovarian cancer, alone or in combination with other factors. The sensitivity, specificity, positive and negative predictive values, and clinical validity of the PROGINS and AR CAG repeat assays are unknown. No recommendations for population-based screening can be made.

Keywords: epidemiology; genetics; ovarian neoplasms; polymorphism (genetics); receptors, androgen; receptors, progesterone; trinucleotide repeats; Abbreviations: AR, androgen receptor; BRCA, breast cancer; CI, confidence interval; OR, odds ratio; PCR, polymerase chain reaction; PGR, progesterone receptor.

Journal Article.  13123 words.  Illustrated.

Subjects: Public Health and Epidemiology

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