Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Delhi 110095, India.
Department of Obstetrics and Gynaecology, University College of Medical Sciences and GTB Hospital (University of Delhi), Delhi 110095, India.
Exp Biol Med (Maywood). 2019 Nov;244(16):1446-1453. doi: 10.1177/1535370219878652. Epub 2019 Sep 30.
The transformation of ovarian surface epithelial cells, stromal cells, sex cord, or germ cells initiates ovarian malignancy. Epithelial ovarian cancer (EOC) is clinically silent with vague, non-specific symptomatology and is generally diagnosed at an advanced stage, resulting in a high mortality rate. The known main etiological factors are: age at menarche and menopause (early menarche or late menopause), use of oral contraception (estrogen and/or progesterone), family history, genetic factors, inflammation, occupational and environmental exposure. The study is intended to assess the association between blood organochlorine pesticide (OCP) levels and polymorphic status of phase I and phase II metabolizing enzymes (CYP1A1, GSTM1, and GSTT1) in the pathogenesis of epithelial ovarian cancer. The study included 200 subjects in total, of which 100 were epithelial ovarian cancer cases and 100 were controls. Estimation of blood organochlorine pesticide levels was carried out using gas chromatography and significantly high levels of beta-hexachlorocyclohexane (β-HCH), endosulfan-I, endosulfan-II, dichlorodiphenyltrichloroethane (pʹpʹ-DDT), dichlorodiphenyldichloroethylene (pʹpʹ-DDE) were observed in cases as compared to controls (-value = 0.029, 0.042, 0.044, 0.039 and 0.037 respectively). For studying the polymorphism of CYP1A1, GSTM1/T1, PCR-RFLP, AS-PCR and multiplexing were performed and the frequency of null deletion of GSTM1/T1 was significantly higher in epithelial ovarian cancer cases. Regression model testing was also performed to check the interactive effect of organochlorine pesticide levels and polymorphic variant of genes keeping CA-125 as the dependent variable and observed a statistically significant role of genotypic/environmental interaction in epithelial ovarian cancer cases in the North Indian population.
Among pervasive environmental toxins, OCPs are one of the largest and most hazardous classes of contaminants in use around the world. Because these compounds possess the estrogen mimicking properties, the accumulation of these compounds in the human body may be a risk for several hormone-dependent diseases. EOC is hormonally dependent cancer and the mortality rate due to this disease is increasingly prevalent, and it has become imperative to explore the role of OCPs in the disease pathogenesis. The present study highlights the significant association of high OCPs level in the disease pathogenesis. It is also observed that the polymorphism in xenobiotic metabolism enzymes alters the predisposition of OCPs. The synergistic effect of gene polymorphism (CYP1A1, GSTM1, and GSTT1) and non-occupational exposure to OCPs was also assessed considering CA125 level as dependent variable with the risk of EOC and concluded that there exist a potential role of genotypic/environmental interaction in the etiology of EOC.
评估血液有机氯农药 (OCP) 水平与上皮性卵巢癌发病机制中 I 相和 II 相代谢酶 (CYP1A1、GSTM1 和 GSTT1) 的多态性之间的关系。
该研究共纳入 200 名受试者，其中 100 名为上皮性卵巢癌病例，100 名为对照组。采用气相色谱法估算血液有机氯农药水平，病例组β-六氯环己烷 (β-HCH)、硫丹-I、硫丹-II、滴滴涕 (pʹpʹ-DDT)、滴滴涕 (pʹpʹ-DDE) 水平明显高于对照组 (-值分别为 0.029、0.042、0.044、0.039 和 0.037)。为研究 CYP1A1、GSTM1/T1 的多态性，采用 PCR-RFLP、AS-PCR 和多重 PCR 法进行检测，上皮性卵巢癌病例中 GSTM1/T1 缺失的频率明显较高。还进行了回归模型检验，以检查 CA-125 作为因变量的有机氯农药水平和基因多态性变异的交互作用，结果显示，在北印度人群中，上皮性卵巢癌病例中存在基因-环境相互作用的统计学显著作用。
在普遍存在的环境毒素中，有机氯农药是全世界使用的最大和最危险的污染物之一。由于这些化合物具有雌激素模拟特性，这些化合物在人体中的积累可能是几种激素依赖性疾病的风险因素。上皮性卵巢癌是一种激素依赖性癌症，其死亡率日益普遍，因此探索有机氯农药在疾病发病机制中的作用势在必行。本研究强调了高水平有机氯农药在疾病发病机制中的显著相关性。还观察到，外源性代谢酶的多态性改变了有机氯农药的易感性。还评估了基因多态性 (CYP1A1、GSTM1 和 GSTT1) 与非职业性有机氯农药暴露的协同作用，考虑到 CA125 水平作为因变量与上皮性卵巢癌的风险，并得出结论，在上皮性卵巢癌的病因学中存在基因-环境相互作用的潜在作用。
