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Estrogen Plus Progestin Use, Microsatellite Instability, and the Risk of Colorectal Cancer in Women

¹ Fred Hutchinson Cancer Research Center and ² Department of Epidemiology, University of Washington, Seattle, Washington; ³ University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin; and ⁴ Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota

Requests for reprints: Polly A. Newcomb, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., P.O. Box 19024, M4-B402, Seattle, WA 98109-1024. Phone: 206-667-3476; Fax: 206-667-7850; E-mail: pnewcomb{at}fhcrc.org.

Current users of postmenopausal hormones (PMH) have 30% to 40% lower risk of colorectal cancer (CRC), although associations with specific types of hormones have been inconsistent. Further, it is not clear whether some tumor types have a different risk. We conducted a case-control study to examine the relationship between PMH and CRC. Cases (n = 1,004), ages 50 to 74 years, were identified from the Surveillance Epidemiology and End Results registry in Washington from 1998 to 2002; controls (n = 1,062) were randomly selected from population lists. Case tissue samples were obtained for microsatellite instability (MSI) analyses. Interviews collected risk-factor data for CRC, including detailed information on PMH. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (95% CI). Current use of any PMH was associated with a 20% reduction in CRC risk (95% CI 0.6–0.9). This reduction in risk was limited to women who had taken estrogen plus progestin (EP) preparations only (OR = 0.6, 95% CI 0.5–0.9); there was no association with estrogen-only (E alone) use (OR = 0.9, 95% CI 0.7–1.1). For women with MSI-low or MSI-stable tumors, there was a statistically significant 40% reduction in CRC risk associated with EP use (95% CI 0.4–0.9); there was no clear association with MSI-high tumors. EP use was associated with a decreased risk of CRC; however, there seemed to be no association with E alone data that are consistent with the recent Women's Health Initiative findings. Progestin may enhance the estrogenic effect of conjugated estrogen so the combination may be more biologically active in the colon than E alone. [Cancer Res 2007;67(15):7534–9]