Bergman-Jungeström M, Gentile M, Lundin A C, Wingren S
Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Int J Cancer. 1999 Aug 20;84(4):350-3. doi: 10.1002/(sici)1097-0215(19990820)84:4<350::aid-ijc3>3.0.co;2-l.
Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T-->C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1-3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1. 9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41-1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women. Int. J. Cancer (Pred. Oncol.) 84:350-353, 1999.
长期暴露于雌激素是乳腺癌一个公认的风险因素，而对于雌激素生物合成和代谢相关基因多态性的影响却知之甚少。一个含有单碱基多态性（T→C，命名为A2等位基因）的候选基因可能是CYP17基因，该基因编码一种参与雌激素合成的酶。这种多态性产生了一个额外的Sp1型启动子位点（CCACC框），已证明其与血清雌激素水平升高有关。我们进行了一项病例对照研究，以评估CYP17基因多态性与年轻女性（小于37岁）患乳腺癌风险的关联。我们发现，至少携带1个A2等位基因的携带者患癌风险有统计学意义的增加[优势比（OR）为2.0；95%置信区间（CI）为1.1 - 3.5，p = 0.027]，并且存在基因剂量效应趋势，表现为A2纯合子受试者（OR为2.8）的风险略高于杂合子女性（OR为1.9）。此外，当我们研究CYP17基因型与肿瘤特征的关系时，携带1个或2个A2等位基因的乳腺癌患者雌激素受体水平往往较低（风险比为0.70；CI为0.41 - 1.2，p = 0.44）。我们的研究结果表明，CYP17基因多态性影响年轻女性的乳腺癌发生。《国际癌症杂志（肿瘤预测）》84:350 - 353，1999年
