Paraoxonase 1 (PON1) Q192R Gene Polymorphism and Cancer Risk: A Meta-Analysis Based on 30 Publications.

ABSTRACT

Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q OR=0.605, 95% CI=0.378-0.967, Pheterogeneity=0.000; RR vs QQ OR=0.494, 95% CI=0.275-0.888, Pheterogeneity=0.002; RQ vs QQ OR=0.465, 95% CI=0.259-0.835, Pheterogeneity=0.000; and RR+RQ vs QQ OR=0.485, 95% CI=0.274-0.857, Pheterogeneity=0.000), and associated with prostate cancer in homozygote (RR vs QQ OR=0.475, 95% CI=0.251- 0.897, Pheterogeneity=0.001) and recessive models (RR vs RQ+QQ OR=0.379, 95% CI=0.169-0.853, Pheterogeneity=0.000), while an increased risk was identified in lymphoma (R vs Q OR=1.537, 95% CI=1.246-1.896, Pheterogeneity=0.944; RR vs QQ OR=2.987, 95% CI=1.861-4.795, Pheterogeneity=0.350; RR+RQ vs QQ OR=1.354, 95% CI=1.021-1.796, Pheterogeneity=0.824; and RR vs RQ+QQ OR=2.934, 95% CI=1.869-4.605, Pheterogeneity=0.433), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ OR=1.782, 95% CI=1.077-2.950, Pheterogeneity=0.000) and dominant models (RR+RQ vs QQ OR=1.281, 95% CI=1.044-1.573, Pheterogeneity=0.056). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ OR=0.601, 95% CI=0.366-0.987, Pheterogeneity=0.000) and dominant models (RR vs RQ+QQ OR=0.611, 95% CI=0.384-0.973, Pheterogeneity=0.000) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q OR=0.788, 95% CI=0.626-0.993, Pheterogeneity=0.000) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest.