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Genetic Variation in CYP19A1 and Risk of Breast Cancer and Fibrocystic Breast Conditions among Women in Shanghai, China

Programs in ¹ Epidemiology, ² Cancer Biology, and ³ Biostatistics, Division of Public Health Sciences, and ⁴ Division of Human Biology, Fred Hutchinson Cancer Research Center; Departments of ⁵ Epidemiology and ⁶ Biostatistics, School of Public Health and Community Medicine, and ⁷ Department of Otolaryngology: Head and Neck Surgery, School of Medicine, University of Washington, Seattle, Washington; ⁸ Department of Epidemiology, Zhongshan Hospital Cancer Center, Fudan University, Shanghai, People's Republic of China; and ⁹ Institute of Medical Biology, University of Tromsø, Tromsø, Norway

Requests for reprints: Chu Chen, Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Mailstop M5-C800, P.O. Box 19024, Seattle, WA 98109-1024. Phone: 206-667-6644; Fax: 206-667-2537. E-mail: cchen{at}fhcrc.org

CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3457–66)