Genetic Variant Arg399Gln G>A of XRCC1 DNA Repair Gene Enhanced Cancer Risk Among Indian Population: Evidence from Meta-analysis and Trial Sequence Analyses

Abstract

The X-ray repair cross-complementation group 1 () gene plays an important role in base excision repair pathway. Several studies have reported contradictory results for exon 10 (Arg399Gln, G23990A, rs25487) gene polymorphism and cancer risk in Indian population, making it difficult to interpret them. Therefore, we have conducted a meta-analysis to evaluate the more precise association between exon 10 G>A gene polymorphism and risk of cancer by published studies. We searched PubMed (Medline) and Google scholar web databases to cover all studies published on association between exon 10 G>A gene polymorphism and cancer risk until August 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. Heterogeneity, publication bias and sensitivity analysis were also assessed. Twenty-five published studies had fulfilled the inclusion criteria comprising 4131 confirmed cancer cases and 5013 controls. When all studies were polled together, overall significant association was found between exon 10 G>A polymorphism and cancer risk in variant allele carrier (A vs. G: OR 1.217, 95% CI 1.056-1.402, = 0.007), homozygous (AA vs. GG: OR 1.359, 95% CI 1.036-1.783, = 0.027), dominant (AA+AG vs. GG OR 1.208, 95% CI 1.006-1.450, = 0.043) and recessive (AA vs. AG+GG: OR 1.315, 95% CI 1.029-1.680, = 0.029) genetic models. Further sensitivity analysis supported the stability of our result by showing similar ORs before and after removal of a single study. The present meta-analysis suggested that the exon 10 G>A polymorphism contribute cancer risk in Indian population, and supports that individuals with risk allele A and AA genotype are at higher risk of developing cancer.

The Association between C194T and G399A Polymorphism of XRCC1 Gene and Susceptibility to Gastric Cancer in Population from Western Iran

“…The main purpose of this study was to investigate the association of 194 and 399 polymorphisms in XRCC1 with susceptibility to gastric cancer in an Iranian population. Gene polymorphisms of XRCC1 may influence DNA repair capacity and thereby contribute to the susceptibility to cancer in humans [23].…”

Glutathione S-Transferase P1 313 (A > G) Ile105Val Polymorphism Contributes to Cancer Susceptibility in Indian Population: A Meta-analysis of 39 Case–Control Studies

“…Individual published studies contained small number of subjects and may have been underpowered to detect the modest effects of the GSTP1 313 (A [ G) polymorphism on cancer susceptibility. To overcome this situation, nowadays meta-analysis statistical tool is used to explore the host risk factors associated with the complex diseases, because it employs a quantitative method to combine the data drawn from individual studies where sample sizes are small to provide reliable conclusions [51]. Given these inconclusive results and the limits of a single study with a small sample size, we performed the present meta-analysis on all eligible published studies in Indian populations to estimate the cumulative association of GSTP1 313 (A [ G) gene polymorphism and overall cancer susceptibility.…”