A common genetic variation in paraoxonase 1 and risk of breast cancer: a literature review, meta-analysis, and in silico analysis

Abstract

Paraoxonase 1 (PON1), an enzyme with multifactorial antioxidant activity, has a protective role against oxidative stress, which is supposed to contribute to the development of cancers including breast cancer. The aim of this study was to examine the correlation of PON1-L55M common genetic polymorphism with the risk of breast cancer in a meta-analysis approach which was followed by an in silico analysis. The eligible studies were collected from valid electronic databases such as Google Scholar, PubMed, Embase, and Web of Science. Quantitative synthesis was performed to report the strength of PON1-L55M polymorphism with breast cancer. Some bioinformatics tools were used to analyze the effects of L55M variation on PON1 gene function. The meta-analysis revealed that there are significant associations between the mentioned polymorphism and breast cancer in M vs. L, MM vs. LL, LM vs. LL, MM + LM vs. LL, and MM vs. LL + LM genetic models. Besides, similar results were observed in the stratified analyses based on ethnicity, genotyping method, Hardy-Weinberg equilibrium in control groups, and sample size. Bioinformatics analysis revealed that the PON1 could be damaging to the protein function. Our findings propose that the PON1-L55M genetic polymorphism might be a genetic risk factor for the risk of breast cancer.