Genetic susceptibility of CYP1A1 gene and risk of pesticide exposure in prostate cancer

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.