Abstract
BackgroundDNA repair gene X-ray repair cross complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity and protection of cells from DNA damage. Sequence variation in XRCC1 gene may alter head and neck cancer (HNC) susceptibility. However, these results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 polymorphism and HNC risk, we undertook a meta-analysis involving 16,344 subjects.MethodsA search of the literature by PubMed, Embase, Web of Science and China National Knowledge Infrastructure was performed to identify studies based on the predetermined inclusion criteria. The odds ratio (OR) with 95% confidence interval (CI) was combined using a random-effects model or a fixed-effects model.ResultsTwenty-nine studies consisting of 6,719 cases and 9,627 controls were identified and analyzed. Overall, no evidence of significant association was observed between XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln genotypes and the risk of HNC in any genetic models. Subgroup analyses according to ethnicity, tumor site, publication year, genotyping method also detected no significant association in any subgroup, except that oral cancer was associated with Arg194Trp variant in recessive model. Furthermore, no significant effect of these polymorphisms interacted with smoking on HNC risk was detected but Arg194Trp homozygous variant.ConclusionIn conclusion, this meta-analysis suggests that the XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism may not involve in HNC susceptibility. Further studies about gene-gene and gene-environment interactions in different populations are required.
Highlights
Head and neck cancer (HNC) is the fifth most common type of cancer in the world [1], with approximately 434,000 new patients diagnosed annually worldwide [2]
Two papers were excluded due to the fact that they did not evaluate the association between head and neck cancer (HNC) risk and X-ray repair cross complementing group 1 (XRCC1) polymorphisms [23,24]
The protein encoded by the XRCC1 gene is a scaffolding protein that associates with DNA ligase I, DNA ligase III, polynucleotide kinase (PNK), DNA polymerase β, and poly polymerase, which are parts of the DNA repair system
Summary
Head and neck cancer (HNC) is the fifth most common type of cancer in the world [1], with approximately 434,000 new patients diagnosed annually worldwide [2]. Accumulative evidence indicates that tobacco smoking, drinking alcohol, and chewing betel quid are three major risk factors for HNC [5,6]. These environmental carcinogens may induce a defective DNA damage response, which may lead to apoptosis or may result in genomic instability and un-regulated (proliferative) cell growth [7,8,9]. Sequence variation in XRCC1 gene may alter head and neck cancer (HNC) susceptibility. Conclusion: In conclusion, this meta-analysis suggests that the XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism may not involve in HNC susceptibility. Further studies about gene-gene and gene-environment interactions in different populations are required
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