Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.
Analytical Chemistry Section, CSIR-Indian Institute of Toxicology Research, M.G. Marg, Lucknow, Uttar Pradesh, India.
Cancer Biomark. 2020;29(4):429-440. doi: 10.3233/CBM-190636.
The etiology of prostate cancer (PCa) is multi-factorial including environmental and genetic factors. Present study evaluates the association between level of pesticides, stress level and CYP1A1 gene polymorphism with PCa patients.
A case control study was conducted with 102 PCa patients and age match symptomatic (n= 107) and asymptomatic benign prostatic hyperplasia (BPH, n= 70) patients. Pesticide level was characterized by Gas Chromatography. The oxidative stress and scavenging mechanisms were determined by biochemical method. Two polymorphisms of CYP1A1 gene, rs4646903 and rs1048943, were analyzed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism and allele specific PCR method.
Higher level of pesticide namely beta-hexachlorocyclohexane (β-HCH), Malathion, Chlorpyrifos and Fenvalerate were found in PCa group (all p value: < 0.05). Kruskal Wallis H test depicted that level of β-HCH and Malathion significantly correlated with higher grade of PCa (all p< 0.05). The PCa Patients with simultaneously low antioxidant activity and high stress level tended to suffer worst clinical outcomes. Dominant model of rs4646903 and rs1048943 suggested that substitution is associated with a higher risk of PCa (OR: 2.2, CI: 1.6-3.8, p: 0.009 and OR: 1.95, CI: 1.1-3.4, p: 0.026; respectively) and this risk was also influenced by smoking and pesticide exposure.
Environmental and genetic factors are reported to raise risk; person with high level of these pesticides especially in high risk genotype might be more susceptible to PCa.
前列腺癌（PCa）的病因是多因素的，包括环境和遗传因素。本研究评估了农药水平、应激水平和 CYP1A1 基因多态性与 PCa 患者之间的关系。
进行了一项病例对照研究，纳入了 102 名 PCa 患者和年龄匹配的有症状（n=107）和无症状良性前列腺增生（BPH，n=70）患者。通过气相色谱法测定农药水平。通过生化方法测定氧化应激和清除机制。采用聚合酶链反应（PCR）结合限制性片段长度多态性和等位基因特异性 PCR 方法分析 CYP1A1 基因的两个多态性，rs4646903 和 rs1048943。
在 PCa 组中发现了更高水平的农药，即β-六氯环己烷（β-HCH）、马拉硫磷、毒死蜱和氰戊菊酯（所有 p 值均<0.05）。Kruskal Wallis H 检验表明，β-HCH 和马拉硫磷的水平与 PCa 的更高分级显著相关（均 p<0.05）。同时抗氧化活性低和应激水平高的 PCa 患者倾向于遭受更差的临床结局。rs4646903 和 rs1048943 的显性模型表明，取代与更高的 PCa 风险相关（OR：2.2，CI：1.6-3.8，p=0.009 和 OR：1.95，CI：1.1-3.4，p=0.026；分别），并且这种风险也受到吸烟和农药暴露的影响。
环境和遗传因素被报道会增加风险；高水平接触这些农药的人，特别是在高危基因型的人群，可能更容易患 PCa。
