Institute of Experimental Medical Research, Department of Molecular Medicine, University of Istanbul, Turkey.
In Vivo. 2010 Jan-Feb;24(1):71-4.
Breast cancer is the commonest cancer among women in industrialized countries. Most sporadic breast carcinomas are likely to be caused by low-penetrance genes. Genes encoding enzymes involved in estrogen and carcinogen metabolism are among these low-penetrance genes. In this study, for the first time the T/C (A1/A2) polymorphism at the 5' untranslated region (UTR) of CYP17 and the Arg/Trp (T/C) polymorphism at codon 39 of CYP19 among genes regulating endogenous estrogen levels was studied.
Fifty-five female breast cancer patients and ninety-one controls took part in the study. DNA was extracted from paraffin-embedded tissues for the patients and from blood cells for the controls. The distribution of genotypes was determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques.
The frequency of the TC genotype of CYP19 was significantly higher in the patient group (p<0.001, kappa(2): 12.31, OR: 7.30, 95% CI: 2.29-25.64). CYP17 frequencies were similar to those in Caucasian populations. In combined analysis, when the high risk alleles were evaluated together, the results reached significance (p=0.006, kappa(2)=7.01, OR: 2.53, %95 CI: 1.26-5.07) for the A2 allele of CYP17 and the C allele of CYP19, being more frequent in the patient group compared to the control. The risk possesed by the TC varient of CYP19 was reduced when evaluated with A1, the protective allele of CYP17 (p=0.082). The cumulative protective effects of both A1 allele and the TT genotype were ascertained to occur significantly less frequently in the patient group (p=0.001, kappa(2): 10.53, OR: 8.47, %95 CI: 1.9-37.04).
The results were consistent with the individual studies of CYP17 and CYP19 in the literature, however, in combined analysis of the alleles of the two genes, the frequency of high risk alleles was higher and the frequencies of low risk alleles were lower in the patient group. The CYP17 A1 + CYP19 TT haplotype may be protective for breast cancer.
乳腺癌是工业化国家中女性最常见的癌症。大多数散发性乳腺癌可能是由低外显率基因引起的。参与雌激素和致癌物代谢的酶的基因就是这些低外显率基因之一。在这项研究中，我们首次研究了调节内源性雌激素水平的基因中 CYP17 的 5'非翻译区（UTR）的 T/C（A1/A2）多态性和 CYP19 密码子 39 的 Arg/Trp（T/C）多态性。
55 名女性乳腺癌患者和 91 名对照参加了这项研究。从患者的石蜡包埋组织和对照的血细胞中提取 DNA。使用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）技术确定基因型分布。
CYP19 的 TC 基因型在患者组中的频率明显较高（p<0.001，kappa(2)：12.31，OR：7.30，95%CI：2.29-25.64）。CYP17 的频率与白种人群相似。在联合分析中，当评估高风险等位基因时，结果达到显著性（p=0.006，kappa(2)=7.01，OR：2.53，95%CI：1.26-5.07），CYP17 的 A2 等位基因和 CYP19 的 C 等位基因在患者组中比对照组更常见。当与 CYP17 的保护性等位基因 A1 一起评估时，CYP19 的 TC 变体的风险降低（p=0.082）。还确定了 CYP19 的 TT 基因型和 CYP17 的 A1 等位基因的累积保护作用在患者组中明显较少发生（p=0.001，kappa(2)：10.53，OR：8.47，95%CI：1.9-37.04）。
结果与文献中 CYP17 和 CYP19 的个体研究一致，然而，在这两个基因的等位基因联合分析中，高风险等位基因的频率在患者组中较高，低风险等位基因的频率在患者组中较低。CYP17 A1 + CYP19 TT 单倍型可能对乳腺癌具有保护作用。
