X-ray repair cross-complementing group 1 Arg399Gln gene polymorphism and susceptibility to colorectal cancer:a meta-analysis

Abstract

X-ray repair cross-complementing group 1 (XRCC1), a DNA repair enzyme, plays a crucial role in the base excision repair by generating a single nucleotide repair patch. It has been demonstrated that the XRCC1 Arg399Gln gene polymorphism was associated with variations in XRCC1 enzyme activity. The aim of this study was to quantitatively summarize the association between the XRCC1 Arg399Gln polymorphism and susceptibility to colorectal cancer (CRC). A comprehensive search of the PubMed, Embase, and China National Knowledge Infrastructure databases was conducted for studies on the association between the XRCC1 Arg399Gln polymorphism and CRC risk. Summary odds ratio (OR) with its corresponding 95 % confidence interval (95 %CI) was estimated, in a fixed-effects model or a random-effects model when appropriate, to assess the association. Totally, 26 case-control studies with 6,979 cases and 11,470 controls were included into this meta-analysis. The pooled results of total studies showed that the XRCC1 Arg399Gln polymorphism was significantly associated with increased risk of CRC in all genetic contrast models (OR(A vs. G) = 1.13, 95 %CI 1.03-1.23, P (OR) = 0.008; OR(Gln/Gln vs. Arg/Arg) = 1.24, 95 %CI 1.04-1.46, P (OR) = 0.015; OR(Gln/Gln vs. Arg/Gln + Arg/Arg) = 1.19, 95 %CI 1.03-1.38, P (OR) = 0.021; OR(Gln/Gln + Arg/Gln vs. Arg/Arg) = 1.14, 95 %CI 1.02-1.28, P (OR) = 0.022), except for the additive contrast model (OR(Arg/Gln vs. Arg/Arg) = 1.11, 95 %CI 0.99-1.25, P (OR) = 0.064). The statistically significant association between the XRCC1 Arg399Gln polymorphism and CRC risk was observed among studies with high quality and in Asians, but not in Caucasians. Sensitivity analyses by sequential omission of any individual studies further identified the significant association. Publication bias was inexistent in this meta-analysis. The meta-analysis suggests that the XRCC1 Arg399Gln polymorphism is associated with increased risk of CRC.

Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

“…Five meta-analyses previously have estimated the association between XRCC1 Arg399Gln polymorphism and CRC susceptibility (Liu et al, 2010;Wu et al, 2013;Zeng et al, 2013;Qin et al, 2015). However, the association remains not fully understood DOI:http://dx.doi.org/10.7314/APJCP.2015.16.8…”

“…Our results are inconsistent with the meta-analysis performed by Zeng et al, which 26 case-control studies with 6,979 cases and 11,470 controls were pooled in the meta-analysis. They have suggested that the XRCC1 Arg399Gln polymorphism was significantly associated with increased risk of CRC in among high quality studies and in Asians, but not in Caucasians (Zeng et al 2013). Lu et al, in a meta-analysis suggests that there is an obvious association between the XRCC1 Arg399Gln polymorphism and increased risk of CRC in East Asians .…”

Association Between the XRCC1 Arg399Gln Polymorphism and Head and Neck Cancer Susceptibility: A Meta-Analysis Based on Case–Control Studies

“…Previous meta-analyses indicated that the XRCC1 Arg399Gln polymorphism is associated with the risk of bladder cancer (Mao et al, 2013), colorectal cancer (Zeng et al, 2013), and lung cancer (Dai et al, 2012). However, this polymorphism is not significantly associated with the risk of esophageal cancer (Li et al, 2013) and gastric cancer (Liu et al, 2012).…”

Low penetrance genetic polymorphisms as potential biomarkers for colorectal cancer predisposition

“…Furthermore, for the c.839G>A (p.Arg280His) polymorphism, a lack of colorectal cancer risk association was reported in a meta‐analysis involving seven studies with 3505 cases and 4636 controls . On the other hand, for the c.1196A>G (p.Gln399Arg) polymorphism, although one meta‐analysis involving 22 studies with 6291 cases and 10 289 controls found a lack of significant risk association, another meta‐analysis involving 26 studies with 6979 cases and 11 470 controls found that the variant allele was associated with an increased colorectal cancer risk . In the latter study, when low quality studies (i.e.…”