Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck

Sturgis, Erich M.; Castillo, E; Li, Lei; Zheng, Rong; Eicher, Susan A.; Clayman, Gary L.; Strom, Sara S.; Spitz, Margaret R.; Wei, Qingyi

doi:10.1093/carcin/20.11.2125

Cited by 267 publications

(169 citation statements)

References 16 publications

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“…Approximately, 30% DNA samples from cases were isolated from surgically resected normal tissues adjacent to the tumors of lung cancer patients. XRCC1 genotypes were analysed by PCR-RFLP methods as described previously (Sturgis et al, 1999;Xing et al, 2002;Hao et al, 2004). The PCR primers for amplifying DNA fragment containing the À77T/C (rs3213245), 194Arg/Trp (rs1799782), 280Arg/His (rs25489), or 399Arg/Gln (rs25487) site were…”

Section: Genotype Analysismentioning

confidence: 99%

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer

et al. 2006

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X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision repair and cells lacking its activity are hypersensitive to DNA damage. Recently, we reported a SNP (rs3213245, À77T>C) in the XRCC1 gene 5 0 untranslated region (UTR) was significantly associated with the risk of developing esophageal squamous-cell carcinoma. Computer analysis predicted that this SNP was in the core of Sp1-binding motif, which suggested its functional significance. Gel shift and super shift assays confirmed that À77T>C polymorphic site in the XRCC1 promoter was within the Sp1-binding motif and the T>C substitution greatly enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced transcriptional activity. The association between À77T>C and three other amino-acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was examined in 1024 patients and 1118 controls and the results showed that only the À77T>C polymorphism was significantly associated with an increased risk of developing lung cancer. Multivariate logistic regression analysis found that an increased risk of lung cancer was associated with the variant XRCC1 À77 genotypes (TC and CC) compared with the TT genotype (OR ¼ 1.46, 95% CI ¼ 1.18-1.82; P ¼ 0.001) and the increased risk was more pronounced in smokers (OR ¼ 1.63, 95% CI ¼ 1.20-2.21) than in non-smokers (OR ¼ 1.28, 95% CI ¼ 0.94-1.76). Taken together, these results showed that the functional SNP À77T>C in XRCC1 5 0 UTR was associated with cancer development owing to the decreased transcriptional activity of C-allelecontaining promoter with higher affinity to Sp1 binding.

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Section: Genotype Analysismentioning

confidence: 99%

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer

et al. 2006

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“…XRCC1 polymorphisms have been associated with SCCHN (Sturgis et al, 1999), pancreatic adenocarcinoma (Duell et al, 2002), lung cancer (Chen et al, 2002) and bladder cancer (Stern et al, 2002). There is also a single report of a significant association with colorectal cancer (reviewed by de Jong et al, 2002).…”

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confidence: 99%

Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer

et al. 2003

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“…In particular, XPD, XRCC1 and XRCC3 have been proposed as polymorphic genes that might be involved in environmental carcinogenesis. [5][6][7][8][9][10] The XRCC1 protein is involved in the base excision-repair pathway, 11 acting apparently as a scaffold protein, facilitating the repair reaction by binding DNA ligase III at its carboxy and DNA polymerase ␤ to its amino terminus. 12 XRCC3 participates in DNA double-strand breaks/recombinational repair and belongs to an emerging family of Rad51-related proteins that participate in homologous recombination (HR) to maintain chromosomal stability.…”

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confidence: 99%

DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study

et al. 2001

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Individuals differ widely in their ability to repair DNA damage, and DNA-repair deficiency may be involved in modulating cancer risk. In a case-control study of 124 bladder-cancer patients and 85 hospital controls (urological and non-urological), 3 DNA polymorphisms localized in 3 genes of different repair pathways (XRCC1-Arg399Gln, exon 10; XRCC3-Thr241Met, exon 7; XPD-Lys751Gln, exon 23) have been analyzed. Results were correlated with DNA damage measured as 32 P-post-labeling bulky DNA adducts in white blood cells from peripheral blood. Genotyping was performed by PCR-RFLP analysis, and allele frequencies in cases/controls were as follows: XRCC1-399Gln ‫؍‬ 0.34/0.39, XRCC3-241Met ‫؍‬ 0.48/0.35 and XPD-751Gln ‫؍‬ 0.42/0.42. Odds ratios (ORs) were significantly greater than 1 only for the XRCC3 (exon 7) variant, and they were consistent across the 2 control groups. XPD and XRCC1 appear to have no impact on the risk of bladder cancer. Indeed, the effect of XRCC3 was more evident in non-smokers [OR ‫؍‬ 4.8, 95% confidence interval (CI) 1.1-21.2]. XRCC3 apparently interacted with the N-acetyltransferase type 2 (NAT-2) genotype. The effect of XRCC3 was limited to the NAT-2 slow genotype (OR ‫؍‬ 3.4, 95% CI 1.5-7.9), suggesting that XRCC3 might be involved in a common repair pathway of bulky DNA adducts. In addition, the risk of having DNA adduct levels above the median was higher in NAT-2 slow acetylators, homozygotes for the XRCC3-241Met variant allele (OR ‫؍‬ 14.6, 95% CI 1.5-138). However, any discussion of interactions should be considered preliminary because of the small numbers involved. Our results suggest that bladder-cancer risk can be genetically modulated by XRCC3, which may repair DNA cross-link lesions produced by aromatic amines and other environmental chemicals. © 2001 Wiley-Liss, Inc. Key words: bladder cancer; XRCC1; XRCC3; XPD; DNA adductsA potentially important source of interindividual variability in response to carcinogens is DNA-repair capability. Apart from rare recessive inherited syndromes such as ataxia-telangiectasia, Fanconi's anemia and Bloom's syndrome, all of which are characterized by both chromosomal instability and high risk of cancer, and xeroderma pigmentosum, characterized by extreme susceptibility to UV-induced skin cancer, 1 individuals differ widely in the ability to repair DNA damage. 2 Polymorphisms in DNA-repair genes have been described. 3,4 Their role in modulating the risk of environmentally induced cancer is potentially important but has been studied only occasionally. In particular, XPD, XRCC1 and XRCC3 have been proposed as polymorphic genes that might be involved in environmental carcinogenesis. [5][6][7][8][9][10] The XRCC1 protein is involved in the base excision-repair pathway, 11 acting apparently as a scaffold protein, facilitating the repair reaction by binding DNA ligase III at its carboxy and DNA polymerase ␤ to its amino terminus. 12 XRCC3 participates in DNA double-strand breaks/recombinational repair and belongs to an emerging family of Rad51-related prot...

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Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck

Cited by 267 publications

References 16 publications

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer

Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer

DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study

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