Association of paraoxonase (PON1) polymorphisms and activity with colorectal cancer predisposition

Abstract

Paraoxonase 1 (PON1) is a well recognised member of human endogeneous free radical scavenging systems and its polymorphism and enzyme activity are attributed to various different cancer formations. We aimed to study the Paraoxonase 1 (PON1) polymorphism and enzyme activity in colorectal cancer patients. Peripheral blood samples for DNA extraction were collected from 54 colorectal cancer patients and 85 healthy individuals. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques were used for determination of the PON1192 polymorphism. The frequency of AA genotype was greater than BB and AB genotypes in all groups (n:65 with 46.8%; n:15 with 10.8% and n:59 with 42.4%, respectively). In both tumor groups, PON activities were significantly lower than the control group (p < 0.05). The AA genotype was significantly more frequent than the AB and BB genotypes in colorectal cancer patients. Although the rectum cancer patients’ number is low in our study, we hypothesise that decreased enzyme activity of PON 1 related to 192 gene polymorphisms might have a role in the formation of an oxidative microenvironment for cancerous DNA damage which may tend to increase distally in the colon. Further studies considering the location and the stage of the colorectal tumors with more patients may put a broadly wider view on this polymorphism and enzyme activity with respect to cancer formation.

Keywords

• paraoxonase 1
• antioxidant
• polymorphism
• colorectal cancer
• predisposition