XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer: a meta-analysis in 17 studies

Abstract

Abstract:Objective: XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted. Methods: Databases including PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q-test was used to test the heterogeneity hypothesis. Egger's test was used to check publication bias. Results: Seventeen published case-control studies that focus on the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC in 2 256 subjects were included in this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall response rate (ORR) was 45.2% (110/243) for AA genotype patients, 29.9% for AG genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test did not show any heterogeneity and the Egger's test did not reveal an obvious publication bias among the included studies. The meta-analysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs. AA model: OR=0.489, P=0.021; AG vs. AA model: OR=0.608, P=0.026; GA+AA vs. GG model: OR=1.259, P=0.135; GG+GA vs. AA model: OR=0.455, P=0.0001). However, no evidence validates XRCC1 associates with the survival following platinum drug therapy. Conclusions: Our meta-analysis suggested that XRCC1 Arg399Gln is related with the sensitivity of NSCLC patients to platinum-based treatment. AA genotype patients present more desirable curative effectiveness compared with other patients.

Analyzing the association between XRCC1 c.1804C>A genetic variant and lung cancer susceptibility in the Chinese population

“…Our data suggested that the allele C contributes to reduced lung cancer susceptibility, and the genotype CC is associated with a protection factor from lung cancer (Table 4). Previously published studies, which reported the influence of several genetic variants in XRCC1 (such as Arg194Trp, Arg280His and Arg399Gln) on the risk of lung cancer, are consistent with our findings that genetic variants in XRCC1 genetically impact lung cancer (Giachino et al, 2007;López-Cima et al, 2007;Sreeja et al, 2008;Chang et al, 2009;Kalikaki et al, 2009;Yin et al, 2009a,b;Butkiewicz et al, 2011;Qian et al, 2011;Chen et al, 2012;Guo et al, 2013). These genetic variants likely affect the function of XRCC1 in base excision DNA repair pathway, which is significantly associated with lung cancer risk (Hao et al, 2006;Giachino et al, 2007;López-Cima et al, 2007;Sreeja et al, 2008;Kalikaki et al, 2009;Yin et al, 2009a,b;Butkiewicz et al, 2011;Qian et al, 2011).…”

“…The genetic factors include candidate genes that might play roles functions in the susceptibility to lung cancer. The XRCC1 gene is an important candidate gene for influencing lung cancer susceptibility (Hao et al, 2006;Giachino et al, 2007;López-Cima et al, 2007;Sreeja et al, 2008;Chang et al, 2009;Kalikaki et al, 2009;Wang et al, 2009;Yin et al, 2009a,b;Butkiewicz et al, 2011;Li et al, 2011;Qian et al, 2011;Chen et al, 2012;Cui et al, 2012;Guo et al, 2013). In the present study, the influence of the XRCC1 c.1804C>A genetic variant on the susceptibility to lung cancer in Chinese Han population was evaluated by association analysis in 348 lung cancer patients and 355 cancer-free control patients.…”

“…It is generally accepted that genetic factors play key roles in the pathogenesis of lung cancer. Previous studies reported that the human X-ray repair complementing group 1 (XRCC1) gene is one of the most important candidate genes for influencing susceptibility to lung cancer (Hao et al, 2006;Giachino et al, 2007;López-Cima et al, 2007;Sreeja et al, 2008;Chang et al, 2009;Kalikaki et al, 2009;Wang et al, 2009;Yin et al, 2009a,b;Butkiewicz et al, 2011;Li et al, 2011;Qian et al, 2011;Chen et al, 2012;Cui et al, 2012;Guo et al, 2013). The potential associations between lung cancer and multiple genetic variants of XRCC1 in different populations have been reported (Hao et al, 2006;Giachino et al, 2007;López-Cima et al, 2007;Improta et al, 2008;Sreeja et al, 2008;Chang et al, 2009;Kalikaki et al, 2009;Yin et al, 2009a,b;Butkiewicz et al, 2011;Qian et al, 2011;Cui et al, 2012;Guo et al, 2013).…”

Association of the XRCC1 c.1178G>A Genetic Polymorphism with Lung Cancer Risk in Chinese

“…Therefore, the allele G and genotype GG may be contribute to play a protection from lung cancer in Chinese, and could be a useful molecular biomarker for assessing the risk of lung cancer. The XRCC1 c.1178G>A genetic polymorphism might be linked to other non-synonymous polymorphisms, such as Arg194Trp, Arg280His, Arg399Gln in XRCC1 gene, which have been approved to associate with the risk of lung cancer (Giachino et al, 2007;Lopez-Cima et al, 2007;Sreeja et al, 2008;Chang et al, 2009;Kalikaki et al, 2009;Butkiewicz et al, 2011;Qian et al, 2011;Chen et al, 2012;. These genetic variants might influence the expression and function of XRCC1 proteins in BER pathway, which has been approved to be associated with lung cancer risk (Hao et al, 2006;Giachino et al, 2007;Lopez-Cima et al, 2007;Sreeja et al, 2008;Kalikaki et al, 2009; .…”

“…However, the exact mechanism of lung cancer remains poorly understood. Recently, many studies have investigated the association of lung cancer with genetic polymorphisms of human X-ray repair cross-complementing group 1 (XRCC1) gene in different populations (Hao et al, 2006;Giachino et al, 2007;Lopez-Cima et al, 2007;Sreeja et al, 2008;Chang et al, 2009;Kalikaki et al, 2009;Wang et al, 2009;Butkiewicz et al, 2011;Huang et al, 2011;Li et al, 2011;PerezMorales et al, 2011;Qian et al, 2011;Rybarova et al, 2011;Chen et al, 2012;Cui et al, 2012;Dai et al, 2012;Karkucak et al, 2012;Ke et al, 2012;Li et al, 2012;Huang et al, 2013;Letkova et al, 2013;Natukula et al, 2013;Ouyang et al, 2013;Sun et al, 2013;Wu et al, 2013;. The XRCC1 proteins play important roles in DNA base excision repair (BER) pathway which may be influence the development of lung cancer.…”