Abstract
BackgroundPrevious studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk.MethodsThe PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals.ResultsNo significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models.ConclusionThe meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.
Highlights
Head and neck cancer (HNC), including cancers in the oral cavity, pharynx, and larynx, is the sixth most common cancer in the world [1]
To analyze the association of the three X-ray repair cross-complementing group 1 (XRCC1) polymorphisms with the risk of head and neck cancer (HNC), 19 studies were selected for Arg194Trp, 24 studies were selected for Arg399Gln, and nine studies were selected for Arg280His
In the subgroup analyses based on ethnicity, cancer site, and whether adjusted or unadjusted for smoking and alcohol, no significant association was found between the XRCC1 Arg399Gln, and Arg280His polymorphisms and HNC risk under the four genetic models
Summary
Head and neck cancer (HNC), including cancers in the oral cavity, pharynx (other than nasopharynx), and larynx, is the sixth most common cancer in the world [1]. Many recent studies have provided evidence that genetic factors including family history [4] and polymorphisms in genes [5,6,7,8] play important roles in the development of HNC. More than 200 single nucleotide polymorphisms (SNPs) have been identified in XRCC1, only three common SNPs have been widely investigated in cancer risk. They are Arg194Trp (rs1799782), Arg280His (rs25489), and Arg399Gln (rs25487), located in exons 6, 9, and 10, respectively, of the XRCC1 gene [3]. Previous studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk
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