P-0022 Association Between C3435T Single Nucleotide Polymorphism of Multi-Drug Resistance 1 Gene and Risk of Gastric Cancer

Abstract

ABSTRACT Introduction Gastric cancer (GC) is the fourth most common cancer in the world and the second leading cause of death due to cancer. The Multi-Drug Resistance 1 (MDR1) gene encodes P-glycoprotein, which confers resistance to antineoplastic drugs, but also affects the kinetic disposition of some drugs and carcinogens. The C3435T polymorphism of the MDR1 gene may influence the transport and excretion of carcinogens, increasing the risk of cancer. The aim of this study was to evaluate the association between this polymorphism and the risk of gastric cancer and tumor aggressiveness. Methods A case-control study was conducted. The case group consisted of patients with non-cardia adenocarcinoma. The control group consisted of healthy subjects. Serology was performed by ELISA for the investigation of infection with Helicobacter pylori. DNA was extracted from peripheral venous blood leukocytes collected with EDTA. The MDR1 polymorphism was analyzed by PCR-RFLP. After amplification, the products were digested with 5 units of the restriction enzyme MboI (New England Biolabs). Genome sequencing was used to confirm the PCR and RFLP techniques using random samples of the two groups. The PCR product of the MDR1 gene was purified using the Big Dye XTerminator Kit and sequenced in an ABI Prism 3100 sequencer. The reverse primer was used for sequencing. The electropherogram was analyzed with the Sequence Scanner v1.0 program. Results Ninety eight patients with non-cardia GC and 203 healthy subjects participated in the study. There was no difference in gender (p=0.12) or age (p=0.125) between the two groups. The genotypes in the control group were in Hardy-Weinberg equilibrium and the frequency of TT, CC and CT genotypes was 19.2%, 33.0% and 47.8%, respectively. In the GC, the frequency of TT, CC and CT genotypes was 15.3%, 32.7% and 52.0%, respectively. No significant difference in the genotypes (p=0.668) or alleles (p=0.745) was observed between the groups. There was no association between the genotypes and the risk of GC in patients infected with H. pylori (p=0.662). Patient survival was not correlated with the genotypes studied (p=0.454). Conclusion The present results provide evidence that the C3435T polymorphism of the MDR1 gene is not associated with GC risk or prognosis in the population studied. No correlation was observed between this polymorphism and infection with H. pylori.