Journal Article

Estrogen Sulfation Genes, Hormone Replacement Therapy, and Endometrial Cancer Risk

Timothy R. Rebbeck, Andrea B. Troxel, Yiting Wang, Amy H. Walker, Saarene Panossian, Stephen Gallagher, Ekaterina G. Shatalova, Rebecca Blanchard, Greta Bunin, Angela DeMichele, Stephen C. Rubin, Mona Baumgarten, Michelle Berlin, Rita Schinnar, Jesse A. Berlin and Brian L. Strom

in JNCI: Journal of the National Cancer Institute

Volume 98, issue 18, pages 1311-1320
Published in print September 2006 | ISSN: 0027-8874
Published online September 2006 | e-ISSN: 1460-2105 | DOI: http://dx.doi.org/10.1093/jnci/djj360

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Background: Unopposed estrogen replacement therapy is associated with increased risk of endometrial cancer. To investigate the mechanism of this association, we evaluated whether risk of endometrial cancer was associated with the genotypes involved in steroid hormone metabolism and the duration of exogenous hormone use. Methods: A population-based case–control study in nine counties of the Philadelphia metropolitan area was undertaken with 502 case patients with endometrial cancer and 1326 age- and race-matched control subjects. Data regarding exogenous hormone use were obtained by interview, and genotypes of the genes COMT, CYP1A1, CYP1A2, CYP1B1, CYP3A4, PGR, SULT1A1, SULT1E1, and UGT1A1 were obtained by polymerase chain reaction techniques. Conditional logistic regression was used to examine the relationship among genotype, hormone use, and endometrial cancer risk. Results: Associations were observed between the risk of endometrial cancer and genotypes of the following steroid hormone metabolism genes: CYP1A1*2C (adjusted odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.08 to 2.61); SULT1A1*3 (adjusted OR = 0.51, 95% CI = 0.29 to 0.92); and the G → A variant in the promoter of SULT1E1 at position −64 (adjusted OR = 1.45, 95% CI = 1.06 to 1.99). We observed a statistically significant interaction between estrogen replacement therapy use and SULT1A1*2 genotype: the SULT1A1*2 allele and long-term use of estrogen replacement therapy were associated with statistically significantly higher risk of endometrial cancer (adjusted OR = 3.85, 95% CI = 1.48 to 10.00) than that of the SULT1A1*2 allele and no estrogen replacement therapy use. Conclusions: Among women with long-term use of estrogen replacement therapy or combined hormone replacement therapy, the risk of endometrial cancer may be associated with functionally relevant genotypes that regulate steroid hormone sulfation.

Journal Article.  8856 words.  Illustrated.

Subjects: Medical Oncology

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