Identification of polymorphisms of XRCC1 gene in patients with cancer in a city of northern Brazil

Artemis Socorro N Rodrigues,Gabriel O Espíndola,Tainá L Vanzeler

doi:10.5935/1676-2444.20150024

Abstract

Introduction: Cancer is considered a genetic disease. For this reason, identification and characterization of the genes involved in its origin and progression are of fundamental importance in understanding its molecular basis. Objective: Our objective was to determine whether people from Macapa with a diagnosis of cancer have genetic polymorphisms related to the XRCC1 gene. Materials and methods: We analyzed 30 samples of deoxyribonucleic acid (DNA) of cases with cancer and 30 control samples. All samples were amplified and analyzed by the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method, with the use of restriction enzyme MspI. Results: Regarding the 194T polymorphism, we found that all samples of the cases presented the polymorphic allele Trp (Arg/Trp). In control samples, 96.6% also identify the polymorphic allele Trp and, among these, one was homozygous for the same allele (Trp/Trp). Regarding the 399A polymorphism, 83.3% of the cases and 23.3% of the controls had the Arg/ Gln genotype, respectively. We found that 73.3% of controls and 16.6% of cases had the Arg/Arg genotype. Among the controls, we found only a sample that was homozygous for the polymorphic allele Trp/Trp. Conclusion: Our results demonstrated the allele frequency of 194Trp polymorphism in both sample groups analyzed. We also found a significant number of polymorphic allele 399A in people with cancer. Thus, we can highlight 399Gln polymorphism as a genetic marker of cancer risk in this population.

Highlights

We found only a sample that was homozygous for the polymorphic allele Trp/Trp (Table, Figure 1 and Figure 2)
It is suggested that polymorphisms in the XRCC1 gene, which cause amino acid changes, would prevent the XRCC1 protein to perform its function effectively and alter the activity of the base excision repair (BER)[7, 9]
It has been reported that polymorphisms in repair genes may increase or reduce the susceptibility to the development of cancer and to treatment with chemotherapeutic agents[1, 4, 5, 7, 10]

Summary

Introduction

The deoxyribonucleic acid (DNA) repair gene XRCC1 (X-ray repair cross complementing family) has an important function in the repair of DNA single-strand breaks induced by oxidation in human cells[1]. The deficiencies in DNA repair capacity due to mutations or polymorphisms of repair genes, including XRCC1, can lead to genomic instability, which results in chromosomal instability syndromes and increased risk of various tumor types[1,2]. These polymorphisms involving an amino acid change in evolutionarily conserved regions can alter the function of XRCC1 protein. Because cancer is a genetic disease, identification and characterization of the genes involved in its origin and progression are of fundamental importance in understanding its molecular basis[3, 4, 7] This better understanding of the disease contributes to new ways to diagnose it early, facilitating treatment[3, 4, 7].

Material and methods

Methodological procedure

Results

Discussion