XPC Lys939Gln polymorphism contributes to colorectal cancer susceptibility: evidence from a meta-analysis.

Qiliu Peng,Xianjun Lao,Zhiping Chen,Xue Qin,Ruolin Li,Weizhong Tang,Shan Li

doi:10.1186/1746-1596-9-120

Abstract

BackgroundPublished studies investigating the association between XPC Lys939Gln polymorphism and colorectal cancer (CRC) risk reported inconclusive results. We performed a meta-analysis to derive a precise estimation of the relationship.MethodsA comprehensive literature search was done in databases PubMed, EMBASE, and Cochrane library up to December 2013. The association between XPC Lys939Gln polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsEight studies with 3,301 cases and 4,177 controls were included in the meta-analysis. We observed that the XPC Lys939Gln polymorphism was correlated with an increased CRC risk when all studies were pooled into the meta-analysis (Gln/lys vs. Lys/Lys: OR = 1.293, 95% CI 1.169–1.430, P = 0.000; Gln/Gln + Gln/lys vs. Lys/Lys: OR = 1.260, 95% CI 1.145–1.388, P = 0.000). In stratified analyses by ethnicity, smoking, and study quality, significant increased CRC risk was found in Asians (Gln/lys vs. Lys/Lys: OR = 1.345, 95% CI 1.187–1.523, P = 0.000; Gln/Gln + Gln/lys vs. Lys/Lys: OR = 1.317, 95% CI 1.170–1.484, P = 0.000), nonsmokers (Gln/Gln + Gln/lys vs. Lys/Lys: OR = 1.286, 95% CI 1.020–1.622, P = 0.033), and high quality studies. In subgroup analysis by source of control, significant increased CRC risk was found in both hospital-based studies and population-based studies. However, in subgroup analysis according to cancer location, no any significant association was detected.ConclusionsThis meta-analysis suggests that the XPC is a candidate gene for CRC susceptibility. The XPC Lys939Gln polymorphism may play an important role in CRC development among Asians and nonsmokers. Further large and well-designed studies are needed to confirm this association.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1665902729125948

Highlights

Published studies investigating the association between xeroderma pigmentosum complementation group C (XPC) Lys939Gln polymorphism and colorectal cancer (CRC) risk reported inconclusive results
Characteristics of studies Based on the search criteria, ten studies investigating the XPC Lys939Gln polymorphism and CRC susceptibility were identified
Meta-analysis As shown in Table 3, we found that the XPC Lys939Gln polymorphism was significantly correlated with increased CRC risk when all studies were pooled into the metaanalysis (Gln/lys vs. Lys/Lys: Odds ratio (OR) = 1.293, 95% Confidence interval (CI) 1.169– 1.430, P = 0.000; Gln/Gln + Gln/lys vs. Lys/Lys: OR = 1.260, 95% confidence intervals (95% CIs) 1.145–1.388, P = 0.000)

Summary

Introduction

Published studies investigating the association between XPC Lys939Gln polymorphism and colorectal cancer (CRC) risk reported inconclusive results. The incidence of CRC is increasing in China, The xeroderma pigmentosum complementation group C (XPC) is one of the key members in the nucleotide excision repair (NER) pathway [9]. Among all the identified SNPs, Lys939Gln polymorphism has received much attention in recent years. It is a substitution of lysine for glutamine in exon 15 of the XPC gene [13], and the variant 939Gln allele have been reported to correlated with reduced DNA repair activity and increased cancer risk [14,15,16]

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Discussion

Conclusion