DNA Repair Gene XRCC1 and XPD Polymorphisms and Gastric Cancer Risk: A Case-Control Study Outcome from Kashmir, India.

Bushra Nissar,Showkat A Kadla,Falaque Ul Afshan,Bashir Ahmad Ganai,Misbah Majid,Idrees A Shah,Nuzhat Shaheen Khan

doi:10.1155/2018/3806514

Abstract

Coding polymorphisms in several DNA repair genes have been reported to affect the DNA repair capacity and are associated with genetic susceptibility to many human cancers, including gastric cancer. An understanding of these DNA repair gene polymorphisms might assess not only the risk of humans exposed to environmental carcinogens but also their responses to different therapeutical approaches, which target the DNA repair pathway. In the present study, polymorphic variants of two DNA repair genes, XRCC1 Arg399Gln and XPD Lys751Gln, were chosen to be studied in association with gastric cancer susceptibility in the Kashmiri population. A total of 180 confirmed cases of gastric cancer (GC) and 200 hospital-based controls from Government Shri Maharaja Hari Singh Hospital, Srinagar, were included in the study. The genotyping for XRCC1 and XPD genes was carried out by polymerase chain reaction-restriction fragment length polymorphism. We found that tobacco smoking is strongly associated with GC risk (OR = 25.65; 95% CI: 5.49–119.7). However, we did not find any association of polymorphism of XRCC1 Arg399Gln (OR = 1.56; 95% CI: 0.32–7.82) and XPD Lys751Gln (OR = 0.46; CI: 0.10–2.19) with GC risk in the study population. The combination of genotypes and gender stratification of XRCC1 and XPD genotypic frequency did not change the results. Consumption of large volumes of salt tea was also not associated with gastric cancer risk. Polymorphic variants of XRCC1 Arg399Gln and XPD Lys751Gln are not associated with the risk of gastric cancer in the Kashmiri population. However, replicative studies with larger sample size are needed to substantiate the findings.

Highlights

Gastric cancer is the fifth most common cancer as regards the prevalence but has the third highest incidence of deaths worldwide [1]
We did not find any significant difference in the minor allele frequencies of X-ray repair cross-complementary 1 (XRCC1) Arg399Gln and xeroderma pigmentosum D (XPD) Lys751Gln between cases and controls (Table 1)
We did not find any significant association of studied polymorphisms of XRCC1 (OR = 1.56; 95% confidence intervals (CIs): 0.32–7.82) and XPD (OR = 0.46; CI: 0.10–2.19) with gastric cancer in the study population

Summary

Introduction

Gastric cancer is the fifth most common cancer as regards the prevalence but has the third highest incidence of deaths worldwide [1]. The XRCC1 protein provides a physical link between the incision and sealing steps of the BER pathway It is a multidomain protein which interacts with the nicked as well as the gapped DNA associated with the DNA pol β, suggesting that this protein might be independently involved in the DNA damage recognition [13]. More than 300 single-nucleotide polymorphisms (SNPs) in the XRCC1 gene have been reported, three SNPs are common, which lead to the amino acid substitution in XRCC1 codon 194 (rs1799782), 280 (rs25489), and 399 (rs25487) These nonconservative amino acid changes may alter the XRCC1 function and increase the chances of DNA damage. The present case-control study was carried out to investigate whether the polymorphisms in the DNA repair genes XRCC1 (Arg399Gln) and XPD (Lys751Gln) modulate the risk of developing GC in Kashmir, which has a relatively high incidence of GC

Subjects and Methods

Results

Discussion