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The CYP19 Gene Codon 39 Trp/Arg Polymorphism Increases Breast Cancer Risk in Subsets of Premenopausal Japanese

¹ Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan; ² Department of Breast Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; and ³ Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya, Japan

Requests for reprints: Kaoru Hirose, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden Chikusa-ku, Nagoya 464-8681, Japan. Phone: 81-52-762-6111; Fax: 81-52-763-5233. E-mail: khirose{at}aichi-cc.jp

The production of estrogen from androgen via the estrogen biosynthesis pathway is catalyzed by aromatase P450 (CYP19). To assess the association between breast cancer risk and a polymorphism at codon 39 Trp/Arg of the encoding gene, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 248 histologically confirmed breast cancer patients and 603 hospital controls without cancer. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by logistic regression analysis. The allele frequency among controls was 3.8% for the C allele, and the OR (95% CI) of the polymorphism relative to TT genotype was 1.21 (0.69-2.14) for TC/CC genotypes combined. There was no association between CYP19 gene polymorphism and breast cancer risk in the study group as a whole, but homozygous and heterozygous carriers of the variant Arg allele showed a significantly increased risk of breast cancer among premenopausal women with a late age at first full-term pregnancy (OR 7.31, 95% CI 1.88-28.5) or a high body mass index (OR 2.77, 95% CI 1.12-6.87). Additional larger studies should be done to confirm that the rare CYP19 variant increases the risk of breast cancer among premenopausal Japanese women.

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