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CYP1A1 多态性与有机氯农药水平在前列腺癌发病机制中的作用。

CYP 1A1 polymorphism and organochlorine pesticides levels in the etiology of prostate cancer.

机构信息

Environmental Biochemistry & Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & GTB Hospital, University of Delhi, Dilshad Garden, Delhi 110 095, India.

出版信息

Chemosphere. 2010 Sep;81(4):464-8. doi: 10.1016/j.chemosphere.2010.07.067.

Abstract

Organochlorine pesticides (OCPs) and polymorphisms of xenobiotic metabolizing enzymes are reported to be associated with the possible risk of prostate cancer. OCPs are endocrine disruptors (EDs) which may act by disrupting the physiologic function of endogenous hormones and therefore possibly increase prostate cancer risk. CYP1A1 metabolizes several carcinogens and estrogens, etc. and hence polymorphism of this gene has been reported to be associated with prostate cancer risk. We studied 70 newly diagnosed prostate cancer patients and 61 age-matched healthy male controls. OCP levels in blood were determined by using gas chromatography-mass spectrometry (GC-MS) and CYP1A1 polymorphisms were analyzed by allele-specific PCR and RFLP-PCR methods. Significantly higher levels of β-HCH, γ-HCH and p,p'-DDE were found in cases as compared to controls (p-values=0.04, 0.008, and 0.01, respectively). Higher levels of γ-HCH were observed in advanced stages of prostate cancer cases (<or=T(2) vs. >or=T(3)), (p-value=0.04). Dieldrin was found significantly higher in cases with initial stages (p-value=0.03). We did not observe any correlation between prostate cancer and CYP1A1 polymorphisms. Hence, higher level of OCPs, especially β-HCH, γ-HCH and p,p'-DDE might be associated with prostate cancer risk.

摘要

有机氯农药 (OCPs) 和外源物质代谢酶的多态性被报道与前列腺癌的可能风险相关。OCPs 是内分泌干扰物 (EDs),可能通过破坏内源性激素的生理功能,从而增加前列腺癌的风险。CYP1A1 代谢多种致癌物质和雌激素等,因此该基因的多态性与前列腺癌风险相关。我们研究了 70 名新诊断的前列腺癌患者和 61 名年龄匹配的健康男性对照。通过气相色谱-质谱联用 (GC-MS) 测定血液中的 OCP 水平,并通过等位基因特异性 PCR 和 RFLP-PCR 方法分析 CYP1A1 多态性。与对照组相比,病例组的β-HCH、γ-HCH 和 p,p'-DDE 水平显著升高 (p 值分别为 0.04、0.008 和 0.01)。在前列腺癌晚期病例中观察到γ-HCH 水平更高 (<或=T(2) 与 >或=T(3)) (p 值=0.04)。初诊病例中狄氏剂水平显著升高 (p 值=0.03)。我们没有观察到前列腺癌与 CYP1A1 多态性之间存在任何相关性。因此,较高水平的 OCPs,特别是β-HCH、γ-HCH 和 p,p'-DDE,可能与前列腺癌的风险相关。

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