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Haplotype Analyses of CYP19A1 Gene Variants and Breast Cancer Risk: Results from the Shanghai Breast Cancer Study

¹ Department of Medicine, Vanderbilt University School of Medicine, ² Vanderbilt Epidemiology Center, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, ³ Department of Biostatistics, Vanderbilt University, Nashville, Tennessee; and ⁴ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

Requests for reprints: Qiuyin Cai, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, B-2104 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232-2400. Phone: 615-936-1351; Fax: 615-322-1754. E-mail: qiuyin.cai{at}vanderbilt.edu

Estrogens play a central role in the etiology of breast cancer. The CYP19A1 gene encodes aromatase, a key enzyme in the biosynthesis of estrogens. Several single nucleotide polymorphisms (SNP) or haplotypes in the CYP19A1 gene have been evaluated in relation to breast cancer risk. However, the results have been inconsistent. In this study, we constructed haplotypes of the CYP19A1 gene using 19 haplotype-tagging SNPs in Chinese women and evaluated the variation of this gene in relation to breast cancer risk in a population-based case-control study involving 1,140 cases and 1,244 community controls of the Shanghai Breast Cancer Study. Five common haplotypes in block 1, three common haplotypes in block 2, five common haplotypes in block 3, and four common haplotypes in block 4 were identified. No apparent association was observed between common haplotypes and breast cancer risk in analyses including all subjects nor in analyses stratified by menopausal status. Similarly, no statistically significant differences were found between cases and controls in the genotype distributions of the 19 individual SNPs and the (TTTA)_n repeat polymorphism evaluated in the study. No overall association of breast cancer risk with common CYP19A1 gene variants among Chinese women was observed in this large-scale, comprehensive study. Further studies are needed to explore CYP19A1 gene-environment interactions in relation to breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(1):27–32)