CYP19(aromatase) haplotypes and breast cancer risk among Japanese women

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The CYP19 gene encodes for aromatase(P450arom) , a key steroidogenic enzyme that catalyzes the final step of estrogen biosynthesis. Apart from rare mutations in CYP19 which result in severe phenotypes associated with estrogen insufficiency, little is known about whether common variation in CYP19 is associated with risk of hormone-related diseases. In this study, we employed a haplotype-based approach to survey common genetic variation across CYP19 gene in relation to circulating postmenopausal steroid levels. Twenty-five haplotype-tagging SNPs were selected from the HapMap database and genotyped using Taqman[○!R] in a study set of Japanese women without any cancers. We determined 7 haplotype blocks(block 1 - block 7) and further investigated the association between haplotype and serum level of estsrone(E1) , estradiol(E2) , testosterone(T) , sex hormone binding globlin(SHBG) , respectively. Block 1 is related to circulating levels of E1 and block 7 is associated with a difference in circulating level of T. These finding suggested that genetic variation in CYP19 gene produces measurable differences in estrogen levels among postmenopausal Japanese women and may contribute to breast cancer risk.