Genetic Polymorphisms of Paraoxonase 1 (PON1) Gene: Association Between L55M or Q192R with Breast Cancer Risk and Clinico-Pathological Parameters

The aim of the present study was to evaluate the association between the paraoxonase 1 (PON1) L55M and Q192R polymorphisms and breast cancer risk as well as clinico-pathological characteristics of the patients. Genotyping of these polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The genotype (P=0.023) and allele (P=0.008) frequencies of L55M polymorphism were significantly different between the breast cancer cases and normal individuals. However, the distribution of genotype (P=0.333) and allele (P= 0.163) frequencies of Q192R polymorphism showed lack of statistical significance. Women who were MM homozygotes (OR=2.229; 95% CI, 1.219-4.075) and carriers of M allele genotype (OR=1.429; 95% CI, 1.035-1.974) or M allele (OR=1.397; 95% CI, 1.093-1.785) were associated with increased risk of breast cancer. However, women who were heterozygous (OR=0.793; 95% CI, 0.567-1.110) or homozygous (OR=0.746; 95% CI, 0.407-1.370) for R allele or carriers of R allele (OR=0.838; 95%, 0.654-1.074) were not associated with breast cancer risk. The M allele genotype was significantly associated with estrogen receptor negativity (P=0.046) and nodal involvement (P=0.004) but R allele genotype was not associated with any of the clinico-pathological characteristics. In conclusion, our findings suggest that the polymorphic variant of L55M polymorphism could be a useful genetic marker for tumor prognosis and to identify women who might be at greater risk of developing breast cancer in a hospital-based Malaysian population.