Cai Hui, Shu Xiao Ou, Egan Kathleen M, Cai Qiuyin, Long Ji-Rong, Gao Yu-Tang, Zheng Wei
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN 37203-1738, USA.
Pharmacogenet Genomics. 2008 Aug;18(8):657-64. doi: 10.1097/FPC.0b013e3282fe3326.
Circulating estrogen levels have been related to the risk of several female cancers. Blood levels of estrogen are controlled by estrogen synthesis enzymes. Genetic variation of estrogen genes thus may influence circulating estrogen levels. We investigated the associations of genetic polymorphisms in CYP19A1, a critical gene involved in estrogen synthesis, with plasma levels of sex hormones among postmenopausal Chinese women.
Included in this study were 345 postmenopausal community controls from a population-based case-control study conducted in Shanghai. Fasting blood samples from those women were measured for blood estradiol, estrone, estrone sulfate, and testosterone. A total of 19 genetic polymorphisms in CYP19A1 were genotyped using ABI7900 or PCR-restriction fragment length polymorphism methods. Differences in plasma levels of hormones by genotype were examined using variance analysis.
The geometric means of plasma levels of estradiol, estrone, estrone sulfate, and testosterone were 10.1, 16.8, 969.0, and 202.9 pg/ml, respectively, for this study population. We found that plasma levels of estrone were associated with rs28566535 (P=0.0180), rs730154 (P=0.0141), and rs936306 (P=0.0274) in block 2. In the same block, the haplotype CGCTA was related to level of estrone (P=0.0064). Single nucleotide polymorphism rs1902584 in block 1 was associated with estradiol only in overweight postmenopausal women. No clear association with sex hormones was noted for the other genetic polymorphisms evaluated in the study.
Single nucleotide polymorphisms in blocks 1 and 2 of the CYP19A1 gene are related to plasma levels of estrogen among postmenopausal Chinese women and may therefore play an important role in the etiology of hormone-related cancers.
循环雌激素水平与多种女性癌症风险相关。雌激素血液水平受雌激素合成酶控制。因此，雌激素基因的遗传变异可能影响循环雌激素水平。我们研究了参与雌激素合成的关键基因CYP19A1中的基因多态性与绝经后中国女性性激素血浆水平之间的关联。
本研究纳入了来自上海一项基于人群的病例对照研究中的345名绝经后社区对照者。测量了这些女性的空腹血样中的血雌二醇、雌酮、硫酸雌酮和睾酮水平。使用ABI7900或聚合酶链反应-限制性片段长度多态性方法对CYP19A1中的总共19种基因多态性进行基因分型。使用方差分析检查不同基因型的激素血浆水平差异。
本研究人群中，雌二醇、雌酮、硫酸雌酮和睾酮的血浆几何平均水平分别为10.1、16.8、969.0和202.9 pg/ml。我们发现，第2模块中的rs28566535（P = 0.0180）、rs730154（P = 0.0141）和rs936306（P = 0.0274）与雌酮血浆水平相关。在同一模块中，单倍型CGCTA与雌酮水平相关（P = 0.0064）。第1模块中的单核苷酸多态性rs1902584仅在超重绝经后女性中与雌二醇相关。在本研究中评估的其他基因多态性未发现与性激素有明显关联。
CYP19A1基因第1和第2模块中的单核苷酸多态性与绝经后中国女性的雌激素血浆水平相关，因此可能在激素相关癌症的病因学中起重要作用。
