Supplementary Figure 1 from High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma
Mei‐Kim AngMihir R. PatelXiaoying YinSneha SundaramKaren FritchieNi ZhaoYufeng LiuAlex J. FreemermanMatthew D. WilkersonVonn WalterMark C. WeisslerW. ShockleyMarion E. CouchAdam M. ZanationTrevor HackmanBhishamjit S. CheraStephen L. HarrisC. Ryan MillerLeigh B. ThorneMichele C. HaywardWilliam K. FunkhouserAndrew F. OlshanCarol G. ShoresLiza MakowskiD. Neil Hayes
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Abstract Background The X‐ray repair cross complementing group 1 ( XRCC1 ) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta‐analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. Recent findings Thirty three studies consisting of 14282 subjects (6012 cases and 8270 controls) were included in this meta‐analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015–1.377, P = 0.032; homozygous model: OR = 1.274, 95%CI = 0.940–1.727, P = 0.119; dominant model: OR = 1.194, 95%CI = 1.027–1.388, P = 0.021; recessive model: OR = 1.181, 95%CI = 0.885–1.576, P = 0.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR‐RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. Objective The X‐ray repair cross complementing group 1 ( XRCC1 ) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta‐analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. Methods A systematic search of the literatures published till April 2022 was conducted using Google Scholar, Scopus, PubMed, Web of Science, Cochrane Library and Embase databases. The heterogeneity was assessed with the I‐Square statistic. A random effects model or fixed effects model was used to analyze the data. Data were reported by odds ratio (OR) and 95% confidence interval (CI). The p value was considered significant if p < .05. Results Thirty three studies consisting of 14 282 subjects (6012 cases and 8270 controls) were included in this meta‐analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015–1.377, p = .032; homozygous model: OR = 1.274, 95%CI = 0.940–1.727, p = .119; dominant model: OR = 1.194, 95%CI = 1.027–1.388, p = .021; recessive model: OR = 1.181, 95%CI = 0.885–1.576, p = .119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR‐RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. Conclusion Variants of XRCC1 Arg194Trp polymorphism were significantly associated with increased risk of HNSCC development based on heterozygous and dominant genetic models.
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XRCC1,a gene directly involved in repair of DNA damage,contains at least three common polymorphisms.It is possible that these polymorphisms may affect DNA repair capacity and efficiency,thus modulate cancer susceptibility.This paper reviews the structure,function of XRCC1 and advances of the relationship between XRCC1 polymorphisms and lung cancer susceptibility.
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Abstract X‐ray repair crosscomplementing group 1 ( XRCC1 ) has a central role in base excision repair (BER) and single‐strand break repair (SSBR). XRCC1 gene polymorphisms (codons 194, 280, and 399) have been identified, and in some cases have been reported to contribute to variations in DNA repair capacity and susceptibility to cancer. To further characterize the effects of XRCC1 gene polymorphisms and their possible interactions with environmental factors on individual levels of DNA damage, we investigated the XRCC1 genotypes of 222 healthy Japanese workers and analyzed data with respect to smoking, drinking habits, age, and health practice index (HPI). Our results showed that poor HPI would associate with a higher level of tail moment (TM). Individuals with one or two XRCC1 R280H variant alleles exhibited significantly higher TM values, and these differences were enhanced by alcohol consumption and aging, whereas smoking and poor HPI may cover up the differences. On the other hand, using a stratified analysis, we found that the XRCC1 R194W variant was associated with a higher TM value in the 40–50 year‐old age group, and the XRCC1 R399Q variant was associated with a lower TM value in the ≤20 pack‐years group or in the 40–50 year‐old age group. These data suggest that XRCC1 polymorphisms could influence individual DNA repair capacity by interacting with lifestyle factors, and specifically, the data indicated that the XRCC1 R280H allele may be more important than codon 194 or 399 alleles. Environ. Mol. Mutagen., 2008. © 2008 Wiley‐Liss, Inc.
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X-ray repair cross complementing I(XRCC1) plays a critical role in repair of single-strand breaks and base damage. So it is considered important in maintaining stability of genome and in the prevention of tumor occurrence. The article reviews the structure and function of XRCC1 gene, the relationship between genetic polymorphisms of XRCC1 and susceptibility to lung cancer, the association between genetic polymorphisms of XRCC1 and response to chemotherapy and radiotherapy,and prognosis in lung cancer. The studies of XRCC1 could offer theoretical reference in prevention and therapy of lung cancer.
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XRCC1; Genetic polymorphism; Lung cancer; Chemotherapy; Radiotherapy
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XRCC1 is an essential protein required for the maintenance of genomic stability through its implication in DNA repair. The main function of XRCC1 is associated with its role in the single-strand break (SSB) and base excision repair (BER) pathways that share several enzymatic steps. We show here that the polymorphic XRCC1 variant R194W presents a defect in its interaction with the DNA glycosylase OGG1 after oxidative stress. While proficient for single-strand break repair (SSBR), this variant does not colocalize with OGG1, reflecting a defect in its involvement in BER. Consistent with a role of XRCC1 in the coordination of the BER pathway, induction of oxidative base damage in XRCC1-deficient cells complemented with the R194W variant results in increased genetic instability as revealed by the accumulation of micronuclei. These data identify a specific molecular role for the XRCC1-OGG1 interaction in BER and provide a model for the effects of the R194W variant identified in molecular cancer epidemiology studies.
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We evaluated the frequency distribution of polymorphic variants in DNA repair genes XRCC1 280, XRCC1 194, XRCC1 399 and XPD 751 gastric cancer patients and healthy controls, leading to new fundamental knowledge and molecular genetic markers of gastric cancer. Statistically significant differences were identified in the two groups for the three excision repair gene XRCC1 280, XRCC1 399 and XPD 751, relative risks were calculated of gastric cancer in carriers of the minor variants of these genes.
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Although the pathogenesis of Hodgkin disease (HD) remains unknown, the results of epidemiologic studies suggest that heritable factors are important in terms of susceptibility. Polymorphisms in DNA repair genes may contribute to individual susceptibility for development of different cancers. However, to the authors' knowledge, few studies to date have investigated the role of such polymorphisms as risk factors for development of HD.The authors evaluated the relation between polymorphisms in 3 nucleotide excision repair pathway genes (XPD [Lys751Gln], XPC [Lys939Gln], and XPG [Asp1104His]), the base excision repair XRCC1 (Arg399Gln), and double-strand break repair XRCC3 (Thr241Met) in a population of 200 HD cases and 220 matched controls. Variants were investigated independently and in combination; odd ratios (OR) were calculated.A positive association was found for XRCC1 gene polymorphism Arg399Gln (OR, 1.77; 95% confidence interval [95% CI], 1.16-2.71) and risk of HD. The combined analysis demonstrated that XRCC1/XRCC3 and XRCC1/XPC polymorphisms were associated with a significant increase in HD risk. XRCC1 Arg/Arg and XRCC3 Thr/Met genotypes combined were associated with an OR of 2.38 (95% CI, 1.24-4.55). The XRCC1 Arg/Gln and XRCC3 Thr/Thr, Thr/Met, and Met/Met genotypes had ORs of 1.88 (95% CI, 1.02-4.10), 1.97 (95% CI, 1.05-3.73), and 4.13 (95% CI, 1.50-11.33), respectively. XRCC1 Gln/Gln and XRCC3 Thr/Thr variant led to a significant increase in risk, with ORs of 3.00 (95% CI, 1.15-7.80). Similarly, XRCC1 Arg/Gln together with XPC Lys/Lys was found to significantly increase the risk of HD (OR, 2.14; 95% CI, 1.09-4.23).These data suggest that genetic polymorphisms in DNA repair genes may modify the risk of HD, especially when interactions between the pathways are considered.
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