Polymorphisms in DNA Damage Response Genes and Head and Neck Cancer Risk

Department of Epidemiology, State University of New York Downstate Medical Center, NY, USA.
Biomarkers (Impact Factor: 2.26). 08/2010; 15(5):379-99. DOI: 10.3109/13547501003797664
Source: PubMed


Polymorphisms in DNA repair genes have been reported contributing factors in head and neck cancer risk but studies have shown conflicting results.
To clarify the impact of DNA repair gene polymorphisms in head and neck cancer risk.
A meta-analysis including 30 case-control studies was performed.
Marginally statistically significant association was found for XRCC1 codon 399 (for Caucasians only), XPD Asp312Asn and XRCC1 codon 194 variants and head and neck cancer.
Assessments of the effects of smoking, alcohol, human papillomavirus and race/ethnicity on the association between DNA repair gene polymorphisms and head and neck cancer are needed.

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Available from: Camille C Ragin
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    • "The XPD Lys751Gln polymorphism (A35931C, rs13181 or rs1052559) is caused by A to C transition at codon 751 in exon 23 of XPD gene resulting in the Gln substitution for Lys. The XPD Lys751Gln polymorphism may lead to reduction in helicase activity and DNA repair capacity and may be important in the carcinogenesis and development of HNC [15,16]. "
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    ABSTRACT: Background: Whether the single nucleotide polymorphism (SNP) Lys751Gln of xeroderma pigmentosum group D (XPD) gene increases susceptibility to head and neck cancer (HNC) is controversial and undetermined. Therefore, we conducted this meta-analysis to systematically assess the possible association between them. Methods: The OVID, Medline, Embase, Pubmed, Web of Science databases were searched to identify the eligible studies. The odds ratio (OR) with 95% confidence interval (95% CI) were used to assess the strength of association. Results: A total of 11,443 subjects from eighteen studies were subjected to meta-analysis. Overall, XPD Lys751Gln polymorphism had no association with increased HNC risk under all five genetic models (P > 0.05). In the subgroup analysis by ethnicity and source of controls, still no significant association was found under five genetic models (P > 0.05). In the subgroup analysis by cancer type, XPD Lys751Gln polymorphism had statistically significant association with elevated laryngeal cancer (LC) and nasopharyngeal cancer (NPC) risk under heterozygous comparison and dominant model (P < 0.05) and borderline significantly increased risk was found under allele contrast for LC and NPC. Carriers of Lys allele and Lys/Lys genotype may be associated with elevated LC and NPC risk. Conclusions: There is overall lack of association between XPD Lys751Gln polymorphism and HNC risk under all five genetic models and still no significant association was found in the subgroup analysis by ethnicity and source of controls. However, XPD Lys751Gln polymorphism was significantly associated with susceptibility to LC and NPC and the Lys allele and Lys/Lys genotype of XPD Lys751Gln polymorphism may be a risk factor for LC and NPC. However, relatively modest sample sizes were included in this meta-analysis and studies with large sample sizes and representative population are warranted to further clarify this finding.
    Full-text · Article · Jan 2014 · Diagnostic Pathology
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    • "Olshan et al. [14] performed a stratified analysis to estimate the interaction between XRCC1 polymorphisms and smoking, suggesting that the Arg194Trp and Arg399Gln variants of XRCC1 were associated with the risk of HNC in those cases, but no association was found in Kumar’s research [15]. Although Flores-Obando et al. [16] performed a meta-analysis in 2010 on the relationship between XRCC1 polymorphisms and the risk of HNC, subgroup analyses of smoking and genotyping method were not performed. Considering these conflicting results, we conducted an updated meta-analysis to deduce a reasonable conclusion about the relationship between XRCC1 polymorphisms and HNC risk. "
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    ABSTRACT: DNA 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. A 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. Twenty-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. 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.
    Preview · Article · Sep 2013 · PLoS ONE
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    • "Recently, a metaanalysis of 15 eligible studies with 3,191 cases and 5,090 controls found some evidence for an association between the Thr241Met SNP and HNC risk [124] . However , another meta-analysis by Flores-Obando et al. revealed that the SNP did not contribute to the risk of HNC [125] . These two different results may be due to the number of studies included in the analyses (15 vs. 10) with various study powers. "
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    ABSTRACT: Although tobacco and alcohol consumption are two common risk factors of head and neck cancer (HNC), other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Human DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic variants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms (SNPs) in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly increased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus interactions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway-based analyses of DNA repair genes derived from genome-wide association studies (GWASs) in HNC are needed.
    Full-text · Article · May 2013
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