PB2066: THE STUDY OF GSTP1 AND MDR1 GENES POLYMORPHISMS IN HODGKIN’S LYMPHOMA AND THEIR LINK WITH CHEMOTHERAPY RESPONSE.

Abstract

Background: Glutathione-S-transferase P1 and ATP-dependent transporter P-glycoprotein are enzymes of the second phase of xenobiotic metabolism that participate in biotransformation of agents of standard protocol of Hodgkin’s Lymphoma chemotherapy. The polymorphism of the GSTP1 and MDR1 genes encoding these proteins causes changes in their activity, which can provide an individual patients’ response to chemotherapy. In this regard, the search for predictive genetic factors for the effectiveness of antitumor therapy is an important task. Aims: to demonstrate the association between polymorphic variants of GSTP1 (A313G, C341T) and MDR1 (C1236T, G2677T, C3435T) genes in patients with Hodgkin’s lymphoma. Methods: Overall, 77 Hodgkin’s lymphoma patients aged 18-74 years who were treated by BEACOPP and ABVD chemotherapy protocols in Oncohematological Departments of City Clinical Hospital №2 and Novosibisk State District clinical Hospital were enrolled in this study. The effectiveness of chemotherapy was evaluated after 4-6 cycles of chemotherapy in accordance with clinical guidelines. Depending on the achieved results of treatment, all patients were divided into two groups: patients with complete/partial remission and patients with progressive/refractory or relapsed lymphoma. Polymorphisms of GSTP1 (A313G, C341T) and MDR1 (C1236T, G2677T, C3435T) genes were defined by PCR method with real-time detection in the samples of peripheral blood in the Centre of Collective Usage «Proteomic analysis» FRC FTM. The odds ratio (OR) used to evaluate the link between genotypes with efficacy of chemotherapy. Results: We found the following frequencies of mutant alleles in Hodgkin’s Lymphoma patients: GSTP1313G – 31.17%, GSTP1 341T – 9.7%, MDR1 1236T – 50.00%, MDR1 2677T – 48.70%, MDR13435 ТОНН – 58.44%. Patient’s genotypes were similar to described genotypes of healthy Europeans. There was no significant difference in distribution of frequency alleles and GSTP1 A313G (χ2=0,89, p=0,34), GSTP1 C341T (χ2=0,11 R=0,74), MDR1 C1236T (χ2=0,01, p=0,93), MDR1 G2677T (χ2=0,37, p=0,54), MDR1 C3435T (χ2=0,01, р=0,97) genotypes between group of Hodgkin’s lymphoma patients with complete/partial remission and group with progressive/refractory or relapsed lymphoma. At the same time we found the significant correlation between GSTP1 A313G heterozygotes and formation of progressive/refractory and prolapsed course of disease (OR = 10.80; CI 95% = 1.23 – 496.52). There was no significant association between efficacy of chemotherapy and other studied genotypes, namely GSTP1 C341T, MDR1 C1236T, MDR1 G2677T, MDR1 C3435T genotypes. Summary/Conclusion: The observed correlation between GSTP1 A313G gene polymorphisms and formation progressive/refractory or prolapsed course of disease needs to be studied to provide safe and effective specific chemotherapy.