Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers

Yu, Lei; Hwang, Shing Jen; Chang, Chuen Chau; Kuo, Hsen Wen; Luo, Jia-Ning; Chang, Ming; Cheng, Tsun‐Jen

doi:10.1016/s1383-5718(02)00127-4

Cited by 93 publications

(50 citation statements)

References 32 publications

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“…We found that Arg/Gln carriers have significantly reduced OS when compared with Arg/Arg carriers. Carriers of the variant Gln allele have been shown to have higher level of DNA adducts (28) and to be a great risk of ionizing radiation sensitivity (29) and tobaccorelated DNA damage (30,31). Moreover, this amino acid substitution (Arg>Gln) produces significant conformational changes at BRTC1 domain (from amino acid 314 to 403) that may be critical for protein-protein interactions (32), thus absence or impairment repair may cause genomic instability and cancer occurrence or outcome.…”

Section: Discussionmentioning

confidence: 99%

Validation of Genetic Sequence Variants as Prognostic Factors in Early-Stage Head and Neck Squamous Cell Cancer Survival

Azad

Bairati

Samson

et al. 2012

Clinical Cancer Research

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Purpose: From the published literature, we identified 23 germ line sequence variants in 17 genes from hypothesis-generating studies that were associated with prognosis of head and neck cancer, including sequence variants of DNA repair (ERCC1, ERCC4, ERCC5, MSH2, XPA, ERCC2, XRCC1, XRCC3), DNA methylation (DNMT3B), cell cycle and proliferation (CCND1, TP53), xenobiotic metabolism (GSTM1, GSTT1, CYP2D6), metastatic -potential (MMP3), immunologic (CTLA4), and growth factor pathways (FGFR4). The purpose of this study was to validate the role of these 23 sequence variants for overall (OS) and disease-free survival (DFS) in a large, comprehensive, well-annotated data set of patients with head and neck cancer.Experimental Design: We genotyped these sequence variants in 531 patients with stage I and II radiation-treated head and neck cancer (originally recruited for an alpha-tocopherol/beta-carotene placebo-controlled secondary prevention study), and analyzed using Cox proportional hazards models, stratified by treatment arm, adjusting for clinical prognostic factors.Results: Two OS associations were statistically significant for each variant allele when compared with the wild-type: CTLA4:A49G [rs231775; adjusted HR (aHR), 1.32 (1.1-1.6); P ¼ 0.01] and XRCC1:Arg339Gln [rs25487; aHR, 1.28 (1.05-1.57); P ¼ 0.02]. Both of these sequence variants had significant results in the opposite direction as prior published literature. Two DFS associations were of borderline significance in the same direction as prior literature: ERCC2:Lys751Gln [rs13181; aHR, 0.80 (0.6-1.0); P ¼ 0.05] and TP53: Arg72Pro [rs1042522; aHR, 1.28 (1.0-1.6); P ¼ 0.03], comparing number of variant alleles with reference of zero variants.Conclusions: None of the prognostic sequence variants previously published was validated for OS in our patients with early-stage radiation-treated head and neck cancer, though rs1381and rs1042522 had borderline significant association with DFS.

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Section: Discussionmentioning

confidence: 99%

Validation of Genetic Sequence Variants as Prognostic Factors in Early-Stage Head and Neck Squamous Cell Cancer Survival

Azad

Bairati

Samson

et al. 2012

Clinical Cancer Research

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“…XRCC1 plays an important role in BER by interacting with a complex of DNA repair proteins, including poly (ADP-ribose) polymerase, DNA ligase 3 and DNA polymerase β (55). The Arg399Gln polymorphism (rs25487) is located at the region of the BRCT-I interaction domain of XRCC1 and is linked with the reduced DRC (56,57). This polymorphism has been extensively investigated for its associations with cancer risk and the results were conflicting in different types of cancer or different populations (58)(59)(60)(61); however, a meta-analysis including 7 studies indicated that Arg399Gln was not significantly associated with SCCHN risk in Caucasians and/or Asians (25), consistent with our findings in this study.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in key DNA repair genes and risk of head and neck cancer in a Chinese population

Yuan

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Although tobacco and alcohol consumption are the major risk factors of head and neck cancer (HNC), genetic variations of genes involved in several biological pathways, such as DNA repair genes, may affect an individual's susceptibility to HNC. However, few studies have investigated the associations between polymorphisms in DNA repair genes and HNC risk in the Chinese population. Thus, we genotyped five common, non-synonymous single-nucleotide polymorphisms (SNPs) [APEX1 (Asp148Glu), XRCC1 (Arg399Gln), ADPRT (Val762Ala), XPD (Lys751Gln) and XPG (His1104Asp)] in a hospital-based, case-control study of 397 HNC cases and 900 cancer-free controls in China. The results showed that none of the five SNPs in the DNA repair pathway was significantly associated with HNC risk, suggesting that these polymorphisms may not play a major role in HNC susceptibility in this Chinese population. IntroductionThe incidence of head and neck cancer (HNC), especially squamous cell carcinoma of the head and neck (SCCHN), has markedly increased in the past 20 years and is now the fifth most common type of cancer worldwide (1). In the United States, it is estimated that there were 48,010 new cases and 11,260 deaths from SCCHN in 2010 (2). Accumulative evidence indicates that exposure to smoking and alcohol consumption are important risk factors of HNC (3); however, only few smokers and drinkers develop HNC, suggesting an individual susceptibility to this cancer in the general population. Most association studies on cancer susceptibility have focused on identifying effects of single-nucleotide polymorphisms (SNPs) in candidate genes of several pathways. Among these, genes involved in the DNA repair pathway are the most investigated due to their vital role in protecting the genome from insults of environmental carcinogens (4,5). Studies have shown inter-individual variations of DNA repair capacity (DRC) in the general population and the effect of a suboptimal DRC on the risk of smoking-related cancers, such as lung cancer and SCCHN (6-8).Of DNA repair pathways, nucleotide excision repair (NER) is the major repair mechanism for the DNA damage caused by tobacco smoking, which deals with a wide class of DNA damages, including bulky adducts cross-links, oxidative DNA damage, thymidine dimers and alkylating damage (9). NER involves more than 20 proteins whose inactivation may lead to xeroderma pigmentosum (XP) or Cockayne syndrome (CS). For example, rare mutations in xeroderma pigmentosum complementation group D and G (XPD and XPG) give rise to a combined XP/CS phenotype and are associated with severe neurological abnormalities.The base excision repair (BER) pathway is another important mechanism that repairs DNA damage resulting from chemical alterations of a single base; a number of proteins are involved in repair steps, such as apurinic/apyrimidinic endonuclease (APE1, also known as APEX1), X-ray repair crosscomplementing 1 (XRCC1) and ADP-ribosyltransferase (ADPRT, also known as PARP1) (10). APE1 is a key member in short-patch BER, w...

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“…[34][35][36] To our knowledge to date, only 5 studies have investigated the association between the XRCC1 399 polymorphism and SCCHN risk in Caucasians, and the findings were not consistent. [18][19][20][21][22] In a pooled study of 555 patients with SCCHN (430 whites) and a group of 792 controls, the XRCC1 399Gln/Gln genotype was associated with decreased risk among whites.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in DNA base‐excision repair genes ADPRT, XRCC1, and APE1 and the risk of squamous cell carcinoma of the head and neck

Lü

et al. 2007

Cancer

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Objective Systemic sclerosis (SSc; scleroderma) is a systemic connective tissue disease with an extensive vascular component that includes aberrant microvasculature and impaired wound healing. The aim of this study was to investigate the presence of antiangiogenic factors in patients with SSc. Methods Plasma samples were obtained from 30 patients with SSc and from 10 control patients without SSc. The samples were analyzed for the ability of plasma to affect endothelial cell migration and vascular structure formation and for the presence of antiangiogenic activity. Results Exposure of normal human microvascular dermal endothelial cells to plasma from patients with SSc resulted in decreased cell migration (mean ± SEM 52 ± 5%) and tube formation (34 ± 6%) compared with that in plasma from control patients (P < 0.001 for both). SSc plasma contained 2.9‐fold more plasminogen kringle 1–3 fragments (angiostatin) than that in control plasma. The addition of angiostatin to control plasma resulted in inhibition of endothelial cell migration and proliferation similar to that observed in SSc plasma. In vitro studies demonstrated that granzyme B and other proteases contained in T cell granule content cleave plasminogen and plasmin into angiostatin fragments. Conclusion Plasminogen conformation in patients with SSc enables granzyme B and granule content protease to limit the proangiogenic effects of plasmin and increase the levels of antiangiogenic angiostatin. This increase in angiostatin production may account for some of the vascular defects observed in patients with SSc.

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Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers

Cited by 93 publications

References 32 publications

Validation of Genetic Sequence Variants as Prognostic Factors in Early-Stage Head and Neck Squamous Cell Cancer Survival

Validation of Genetic Sequence Variants as Prognostic Factors in Early-Stage Head and Neck Squamous Cell Cancer Survival

Genetic polymorphisms in key DNA repair genes and risk of head and neck cancer in a Chinese population

Genetic polymorphisms in DNA base‐excision repair genes ADPRT, XRCC1, and APE1 and the risk of squamous cell carcinoma of the head and neck

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