Paraoxonase 1 Genetic Polymorphisms and Susceptibility to Breast Cancer: a Meta-analysis

Aim: The paraoxonase 1 gene (PON1, MIN: 168820) is a member of the multifactorial antioxidant enzyme paraoxonase family (EC 3.1.1.2). Two common functional single-nucleotide polymorphisms L55M (dbSNP: rs854560) and Q192R (dbSNP: rs662) have been identified in the coding region of PON1. Several studies have investigated the associations between polymorphisms of PON1 and susceptibility to breast cancer, but have yielded apparently conflicting results. We therefore carried out a meta-analysis of published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between PON1 gene variants and breast cancer risk.

Method: Overall six eligible studies were identified. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using fixed and random-effect models.

Results: In our meta-analysis, the presence of the R allele was associated with decreased risk of breast cancer (QR+RR compared to QQ genotype, summary OR=0.57, 95% CI: 0.49-0.67, P<0.001). Both heterozygosity (OR=1.32, 95% CI: 1.10-1.58, P=0.002) and homozygosity (OR=2.16, 95% CI: 1.75-2.68, P<0.001) for the 55M allele were associated with increased risk of breast cancer. Also there was a significant linear trend in risk associated with zero, one, and two 55M alleles (χ(2)=54.2, P<0.001).

Conclusion: The present study showed that PON1 M and Q alleles are associated with a higher risk of breast cancer. Individuals having MM and QQ genotypes have a lower level and lower detoxification activity of the PON1 enzyme, which may increase the vulnerability of the breast to genetic damage by reducing the ability to detoxify inflammatory oxidants, as well as dietary carcinogens.