PARAOXONASE 3 POLYMORPHISMS ARE NOT ASSOCIATED WITH PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL IN DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma. It is a heterogeneous disease. Approximately 40% of the patients respond well to chemotherapy based on rituximab-CHOP (R-CHOP). The prognosis for the other 60% is poor and only half of the patients survive 5 years after the onset of the disease. The paraoxonase (PON) gene family is composed of three members (PON1, PON2, PON3). All the three proteins have been shown to exhibit antioxidant and anti-inflammatory properties. Evidences exist indicating that the PON family plays an important role in a variety of human illnesses such as cardiovascular disease, diabetes mellitus, metabolic syndrome, obesity, non-alcoloholic steatohepatitis and several mental disorders. However, their role inDLBCL is still unknown. Methods: 106 DLBCL patients treated with R-CHOP or CHOP were studied. Control group included 130 healthy blood donors. Blood was drawn and DNA extracted by conventional methods. Polymorphisms of PON3 were performed by real time polymerase chain reaction using TaqMan system. Results: Forty-six (43.4%) patients were in stage III-IV and 42 (39.6%) had more than 2 factors established by the International Prognostic Index (IPI). Seventy-nine (74.5%) achieved complete response (IC95%: 77-93%); 6 (5.6%) had partial response (RD) and 21 (19.9%) patients had refractory disease. Eighteen (16.9%) patients died in a follow up median of 29.6 months (5.5 to 72.7). Polymorphisms frequencies in control group were:76% and 24%, respectively, for the alleles PON3-10340T and PON3-10340G; 8% and 92%, respectively, for the alleles PON3-2115A and PON3-2115T; and 4% and 96%, respectively, for the alleles PON3-45486A and PON3-45486C. The frequencies in the group of patients were: 76% and 24% for the alleles PON3-10340T and PON3-10340G, respectively; 9% and 91% for the alleles PON3-2115A and PON3-2115T, respectively; and 1% and 99% for the alleles PON3-45486A and PON3-45486C, respectively. Fisher exact test showed no significant difference between groups. The overall response and progression-free survival of patients with DLBCL were not related to PON3 polymorphisms. Conclusion: The present data shows that PON3 polymorphisms do not play a role in diffuse large B-cell lymphoma.