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

Abstract

Background: Colorectal cancer (CRC) is a leading cause of cancer-related death. Oxidative DNA damage may contribute to cancer risk and the antioxidant paraoxonase is one endogenous free radical scavenger in the human body which could therefore exert an influeence. Purpose: Aim of this study was to determine the role of serum arylesterase (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 in CRC patients will be investigated before and after surgery Materials and Methods: This study involved a total of 50 patients with newly diagnosed CRC and 80 healthy controls. PON1 and ARE activities were determined using an enzymatic spectrophotometric method. PON1 Q192R and L55M gene polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based restriction fragment analysis. The restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Results: Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the controls. Significant differences were found in the L55M polymorphism. Additionally, there were significant differences in L and M allele frequencies (p=0.001). The serum activities of PON1 and ARE were low in QQ and MM genotype. Conclusions: serum PON1 and ARE activities were significantly lower in CRC patients compared to healthy subjects. The R allele may protect against colorectal cancer.

Evaluation of Association Between Q192R and L55M Genetic Polymorphisms of PON1 and Serum Paraoxonase-1 Activity in Healthy Individuals, a Meta-Analysis

“…The studies were conducted on different ethnic populations: 18 studies included a Caucasian population, 7 studies included an Asian population (Table 1), and 6 studies included an African population. The genotyping frequencies in the participants showed significant differences with the expected frequencies in five studies [24,25,33,36,45]. These studies were excluded from meta-analysis.…”

Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients

“…For example, decreased serum PON1 activity and increased levels of lipid peroxidation have been reported in 45 Pakistani patients with oral squamous cell carcinoma [ 29 ], and 30 Turkish patients with esophageal squamous cell carcinoma [ 30 ], and a further 25 Turkish patients with papillary thyroid cancer [ 31 ]. The activity of PON1 enzyme was shown to be low in 50 Egyptian patients with colorectal cancer but with significant increases one month post-surgery [ 32 ]; similar to 49 French patients with BC recurrence [ 33 ]. This latter study also showed an inverse relationship between serum PON1 activity and serum amyloid A concentrations.…”

Association between L55M polymorphism in Paraoxonase 1 and cancer risk: a meta-analysis based on 21 studies

“…A total of six cancer types were addressed: four studies on breast cancer; three on prostate cancer; two on colorectal cancer, lung cancer, and ovarian cancer; and eight on other cancers (one study each on acute leukemia, brain tumor, embryonal tumor, hepatocellular carcinoma, lymphohematopoietic cancer, osteosarcoma, renal cell carcinoma, and pancreatic cancer). All genotype frequencies were in HWE with the exception of Antognelli et al 16 and Ahmed et al, 21 and these two studies were excluded from the pooled analyses.…”