Department of Microbiology, Medical Microbiology Laboratory, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620 024, Tamil Nadu, India.
Arch Gynecol Obstet. 2013 Dec;288(6):1385-90. doi: 10.1007/s00404-013-2892-y. Epub 2013 May 31.
Alteration and overexpression of HER2 proto-oncogene have been implicated in the carcinogenesis and prognosis of ovarian cancer. We evaluated this hypothesis among women with ovarian carcinoma patients from Tiruchirapalli, Tamil Nadu, India.
Genomic DNA was extracted from 72 case patients and 288 control subjects and was examined for I655V polymorphism by PCR-RFLP based assay. Immunohistochemistry analysis was carried out in order to study the overexpression of HER2 protein. The observed number of each genotype was compared with that expected for a population in the Hardy-Weinberg equilibrium. In analysing the relation between genotype and overexpression of HER2 protein, Cochran-Mantel-Haenszel statistics was used.
We found that 20.8% of the case patients and 16.3% of the control subjects were heterozygous for the Val allele and 10 case patients (13.8%) and 3 control subjects (1.1%) were homozygous for this allele (P < 0.001). Compared with women with Ile/Ile genotype, women with Val/Val genotype had an elevated risk of ovarian cancer. The genotype distributions were consistent with the Hardy-Weinberg equilibrium. The risk increased with the number of Val allele and women homozygous for the Val allele had 15-fold (OR = 15.3; 95%CI = 4.09-57.31) increased risk of cancer. The patients homozygous for the Valine allele showed strong HER2 protein expression.
The results showed that the valine allele may be an indicator of genetic susceptibility to ovarian carcinoma in the study population.
HER2 原癌基因的改变和过表达与卵巢癌的发生和预后有关。我们在来自印度泰米尔纳德邦蒂鲁吉拉伯利的卵巢癌患者中评估了这一假说。
从 72 例病例患者和 288 例对照中提取基因组 DNA，并用基于 PCR-RFLP 的检测方法检测 I655V 多态性。进行免疫组织化学分析以研究 HER2 蛋白的过表达。观察到的每种基因型的数量与人群在 Hardy-Weinberg 平衡中的预期数量进行比较。在分析基因型与 HER2 蛋白过表达之间的关系时，使用 Cochran-Mantel-Haenszel 统计。
我们发现 20.8%的病例患者和 16.3%的对照者为 Val 等位基因的杂合子，10 例病例患者（13.8%）和 3 例对照者（1.1%）为纯合子（P <0.001）。与 Ile/Ile 基因型的女性相比，Val/Val 基因型的女性患卵巢癌的风险增加。基因型分布与 Hardy-Weinberg 平衡一致。风险随 Val 等位基因数量的增加而增加，纯合 Val 等位基因的女性患癌症的风险增加 15 倍（OR=15.3；95%CI=4.09-57.31）。纯合 Valine 等位基因的患者表现出强烈的 HER2 蛋白表达。
结果表明，在研究人群中，Val 等位基因可能是卵巢癌遗传易感性的指标。
