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

CYP19基因编码芳香酶(P450arom)，这是一种关键的类固醇合成酶，催化雌激素生物合成的最后一步。除了罕见的CYP19突变会导致雌激素不足的严重表型外，关于CYP19的常见变异是否与激素相关疾病的风险有关还知之甚少。在这项研究中，我们采用了一种基于单倍型的方法来调查CYP19基因上常见的遗传变异与循环中的绝经后类固醇水平的关系。从HapMap数据库中选择了25个单倍型标记SNPs，并使用Taqman[0！R]在一组没有任何癌症的日本妇女中进行了基因分型。我们测定了7个单倍型块(块1-块7)，并进一步研究了单倍型与血清雌二醇(E_1)、雌二醇(E_2)、睾酮(T)、性激素结合球蛋白(SHBG)水平的关系。阻断1与循环中的E1水平有关，阻断7与循环中的T水平的差异有关。这些发现表明，CYP19基因的遗传变异导致绝经后日本妇女雌激素水平的显著差异，并可能导致乳腺癌的风险。

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.