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1 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center; 2 Department of Epidemiology, School of Public Health and Community Medicine, and 3 Department of Otolaryngology: Head and Neck Surgery, School of Medicine, University of Washington, Seattle, Washington
Requests for reprints: Chu Chen, Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024 (M4-C308), Seattle, WA 98109-1024. Phone: 206-667-6644 Fax: 206-667-5948. E-mail: cchen{at}fhcrc.org
2-Hydroxylated metabolites of estrogen have been shown to have antiangiogenic effects and inhibit tumor cell proliferation, whereas 4-hydroxylated metabolites have been implicated in carcinogenesis. We examined whether polymorphisms in certain genes involved in estrogen metabolism are associated with endometrial cancer risk in a population-based case-control study with 371 cases and 420 controls. Based on previously published genotype-phenotype correlation studies, we defined variant alleles thought to increase estrogen 2-hydroxylation as presumptively low-risk (CYP1A1 m1 T6235C and m2 Ile462Val) and those thought to increase estrogen 4-hydroxylation as high-risk (CYP1A1 m4 Thr461Asn, CYP1A2 A734C, and CYP1B1 Leu432Val). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression. Carrying at least one CYP1A1 m1 or m2 variant allele was associated with a decreased risk of endometrial cancer [ORs (95% CIs), 0.64 (0.44-0.93) and 0.54 (0.30-0.99), respectively]. No strong alteration in risk was observed among women with any of the putative high-risk alleles. When CYP1A1, CYP1A2, and CYP1B1 genotypes were combined and ranked by the number of putative low-risk genotypes carried, women with four or five low-risk genotypes had a reduced risk of endometrial cancer (OR, 0.29; 95% CI, 0.15-0.56) compared with women with one or none. No appreciable alteration in risk was observed among women carrying two or three low-risk genotypes. Some of our findings are consistent with the hypothesis that increased estrogen 2-hydroxylation is associated with decreased endometrial cancer risk, but replication of these results is required before any firm conclusions can be reached.
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