Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk
Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk
复制标题
DOI：
10.1097/01.fpc.0000189803.34339.ed
复制
发表时间：
2006-04-01
影响因子：
2.6
通讯作者：
Zheng, Wei
中科院分区：
文献类型：
--
作者：
Long, Ji-Rong;Egan, Kathleen M.;Zheng, Wei
芳基碳氢化合物受体 (AhR) 是细胞色素 P450 1 (CYP1) 基因转录表达的关键调节因子。 CYP1A2 是催化雌激素 2-羟基化的主要 CYP1 酶之一，雌激素是一种在乳腺癌病因学中发挥关键作用的激素。在这项研究中，我们在 1090 例病例和 1183 例对照中调查了这两个基因中的两个常见多态性 CYP1A2* 1F 和 AhR Lys554Arg 是否与乳腺癌风险相关，这是基于人群的病例对照研究（上海乳腺癌研究）的一个子集。对 236 名研究对象进行了体内咖啡因测试，以研究这两种多态性与 CYP1 A2 活性的关系。对于 AhR 基因，A (Lys) 等位基因与乳腺癌风险降低相关。以 GG 基因型为参考，AG 基因型的比值比为 0.82 [95% 置信区间 (CI) = 0.69-0.99]，AA 基因型的比值比为 0.76 (95% CI = 0.58-1.01)（趋势 P = 0.018）。然而，尽管发现 CYP1A2* 1F 多态性与 CYP1A2 活性相关，但未观察到 CYP1A2 基因型与乳腺癌风险之间存在关联。 CC、AC 和 AA 基因型的咖啡因代谢物比率的几何平均值分别为 2.90、2.30 和 1.95（趋势 P = 0.024）。总之，我们的研究结果表明，AhR Lys554Arg 多态性可能是乳腺癌的遗传易感因素，而 CYP1A2* 1F 是一种潜在的功能性单核苷酸多态性，可能与乳腺癌风险无关。
The aryl hydrocarbon receptor (AhR) is a key regulator of the transcriptional expression for the cytochrome P450 1 (CYP1) genes. CYP1A2 is one of the major CYP1 enzymes that catalyse 2-hydroxylation of estrogen, a hormone that plays a critical role in the etiology of breast cancer. In this study, we investigated whether two common polymorphisms in these two genes, CYP1A2* 1F and AhR Lys554Arg, were associated with breast cancer risk in 1090 cases and 1183 controls, a subset of the population-based case-control study, the Shanghai Breast Cancer Study. Caffeine tests were performed in vivo in a subset of 236 study subjects to investigate the relationship of these two polymorphisms with CYP1 A2 activity. For the AhR gene, the A (Lys) allele was associated with a decreased risk of breast cancer. Using the genotype GG as reference, odds ratios of 0.82 [95% confidence interval (CI) = 0.69-0.99] for the AG genotype and 0.76 (95% CI = 0.58-1.01) for the AA genotype (P for trend = 0.018) were obtained. However, no association was observed between CYP1A2 genotypes and breast cancer risk, although the CYP1A2* 1F polymorphism was found to be related to CYP1A2 activity. The geometric mean values for the caffeine metabolites ratio were 2.90, 2.30, and 1.95 for CC, AC, and AA genotypes, respectively (P for trend = 0.024). In conclusion, the results from our study suggest that the AhR Lys554Arg polymorphism may be a genetic susceptibility factor for breast cancer, whereas CYP1A2* 1F, which is a potentially functional single nucleotide polymorphism, may not be related to breast cancer risk.