Multi-drug resistance 1 genetic polymorphism and prediction of chemotherapy response in Hodgkin's Lymphoma

Nizar M Mhaidat,Ahmad N Aldaher,Osama Y Alshogran,Ismail I Matalka,Omar F Khabour,Karem H Alzoubi,William J Haddadin,Ibraheem O Mahasneh

doi:10.1186/1756-9966-30-68

Abstract

BackgroundThe human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient's response to ABVD chemotherapy regimen.Methodsa total of 130 paraffin embedded tissue samples collected from HL patients were analyzed to identify the C3435T polymorphism. As a control group, 120 healthy subjects were enrolled in the study. The C3435T Polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism.Resultsthese studies revealed that the frequency of T allele was significantly higher in HL patients compared to the controls (P < 0.05). In addition, the frequency of CT and TT genotypes were also significantly higher in HL patients compared to the controls (P < 0.05). No association between C3435T polymorphism and response to ABVD was detected among HL patients (P > 0.05).Conclusionsthese results suggest that MDR1 C3435T polymorphism might play a role in HL occurrence; however this polymorphism is not correlated with the clinical response to ABVD.

Highlights

The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy
We investigated the association between the MDR1 C3435T polymorphism and the risk to develop Hodgkin lymphoma (HL), as well as the clinical response to ABVD chemotherapy regimen
To verify whether different baseline characteristics of the patients might contribute to chemotherapy response, complete remission and disease relapse were studied according to the following criteria: age, gender, specimen histology, disease stage and presence or absence of Bsymptoms (Table 5)

Summary

Introduction

The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. We studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient’s response to ABVD chemotherapy regimen. While more than 70% of HL patients are cured after treatment [3], about 30% of them might experience relapse after achieving initial complete remission (CR) [4]. This was attributed to the development of drug resistance, which might result from change in drug target sites or increased drug efflux by overexpression of drug transporters [5,6,7]

Methods

Results

Conclusion