Association of Paraoxonase-1(Q192R and L55M) Gene Polymorphisms and Activity with Colorectal Cancer and Effect of Surgical Intervention


Background: Colorectal cancer (CRC) is a leading cause of cancer-related death. Oxidative DNA damage maycontribute to cancer risk and the antioxidant paraoxonase is one endogenous free radical scavenger in the humanbody which could therefore exert an influeence. Purpose: Aim of this study was to determine the role of serumarylesterase (ARE) and paraoxonase 1(PON1) activities in CRC patients and to find any association between(PON1) Q192R and L55M gene polymorphisms in CRC patients. Also the serum ARE and PON1 activities inCRC patients will be investigated before and after surgery Materials and
Methods: This study involved a total of50 patients with newly diagnosed CRC and 80 healthy controls. PON1 and ARE activities were determined usingan enzymatic spectrophotometric method. PON1 Q192R and L55M gene polymorphisms were determined usingpolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based restriction fragmentanalysis. The restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55Mpolymorphism.
Results: Significant differences in the PON1 Q192R polymorphism were found between patientsand controls. The Q allele was more frequent in the patient group than in controls, while the R allele was morefrequent in the controls. Significant differences were found in the L55M polymorphism. Additionally, there weresignificant differences in L and M allele frequencies (p=0.001). The serum activities of PON1 and ARE werelow in QQ and MM genotype.
Conclusions: serum PON1 and ARE activities were significantly lower in CRCpatients compared to healthy subjects. The R allele may protect against colorectal cancer.