Defective nucleotide excision repair in Xpc mutant mice and its association with cancer predisposition

Friedberg, Errol C.; Bond, Jeffrey P.; Burns, Dennis K.; Cheo, David L.; Greenblatt, Marc S.; Meira, Lisiane B.; Nahari, Dorit; Reis, Antonio

doi:10.1016/s0921-8777(99)00068-3

Cited by 81 publications

(52 citation statements)

References 33 publications

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“…Two independently generated knockout mouse models for Xpc [69] and [70] were shown to be viable and to develop normally. Although initially, no increased incidence of spontaneous tumors was observed in Xpc-deficient animals until the age of one year [69], [70] and [71], a more recent study of Hollander et al [72] showed an enhanced frequency of lung tumor development in Xpc −/− mice. All aged (16-17 months) Xpc −/− mice (in a mixed background of 75% C57BL/6 and 25% Ola129) developed multiple spontaneous lung tumors with a minority progressing to non-small cell lung adenocarcinoma, whereas only 5% of wild type littermates developed such tumors [72].…”

Section: Mouse Models With a Defect In Gg-nermentioning

confidence: 93%

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

Wijnhoven

Hoogervorst

Waard

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Several mouse models with defects in genes encoding components of the nucleotide excision repair (NER) pathway have been developed. In NER two different sub-pathways are known, i.e. transcription-coupled repair (TC-NER) and global-genome repair (GG-NER). A defect in one particular NER protein can lead to a (partial) defect in GG-NER, TC-NER or both. GG-NER defects in mice predispose to cancer, both spontaneous as well as UV-induced. As such these models (Xpa, Xpc and Xpe) recapitulate the human xeroderma pigmentosum (XP) syndrome. Defects in TC-NER in humans are associated with Cockayne syndrome (CS), a disease not linked to tumor development. Mice with TC-NER defects (Csa and Csb) areexcept for the skin -not susceptible to develop (carcinogen-induced) tumors. Some NER factors, i.e. XPB, XPD, XPF, XPG and ERCC1 have functions outside NER, like transcription initiation and inter-strand crosslink repair. Deficiencies in these processes in mice lead to very severe phenotypes, like trichothiodystrophy (TTD) or a combination of XP and CS. In most cases these animals have a (very) short life span, display segmental progeria, but do not develop tumors. Here we will overview the available NER-related mouse models and will discuss their phenotypes in terms of (chemical-induced) tissue-specific tumor development, mutagenesis and premature aging features.

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Section: Mouse Models With a Defect In Gg-nermentioning

confidence: 93%

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

Wijnhoven

Hoogervorst

Waard

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…The Excision repair cross complementing group 5 (XPG or ERCC5) gene encodes an 1186-amino acid structure-specific endonuclease that is essential for the two incision steps in NER (Mueser et al, 1996;Friedberg et al, 2000). The additional functions of XPG are evident by the presence of structural motifis that are common with proteins involved in repair-recombination and cell cycle regulation (Klungland et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

SNPs of Excision Repair Cross Complementing Group 5 and Gastric Cancer Risk in Chinese Populations

Yang¹,

Zhang²,

Chen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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We conducted a case-control study to determine the association between several potential SNPs of excision repair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphisms in combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newly diagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>T and rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147 CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258 TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258 TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CC was associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findings suggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, but the effect needs to be further validated by larger sample size studies.

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“…13 The XPC-HR23B complex functions as an early damage detector and a molecular matchmaker for recruitment of other components of the repair apparatus to the damaged DNA in global genomic NER. 14,15 Mice defective in the XPC gene are highly prone to skin cancer following exposure to UV radiation and highly vulnerable to cancers of the internal organs, such as liver and lung, when exposed to chemical carcinogens, 16,17 suggesting that XPC is important for preventing carcinogenesis. Several polymorphisms in the XPC gene have been reported [18][19][20][21] and listed in public databases (e.g., http://www.ncbi.nlm.nih.gov/ SNP).…”

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confidence: 99%

XPC polymorphisms and lung cancer risk

Lee

Jang

Lee

et al. 2005

Intl Journal of Cancer

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Polymorphisms in DNA repair genes may be associated with differences in the capacity to repair DNA damage and thereby influence an individual's susceptibility to smoking-related cancer. To test this hypothesis, we investigated the potential association of 7 XPC polymorphisms (-449G?C, -371G?A, -27G?C, Val499-Arg, PAT-/+, IVS11-5C?A and Lys939Gln) and their haplotypes with lung cancer risk in a Korean population. XPC genotypes were determined in 432 lung cancer patients and 432 healthy controls frequency-matched for age and sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase program. The combined -27CGþCC genotype was associated with a significantly increased risk for overall lung cancer compared to the -27GG genotype (adjusted OR = 1.97, 95% CI 1.22-3.17, p = 0.005). The other 6 polymorphisms were not significantly associated with overall risk of lung cancer. When lung cancer cases were categorized by tumor histology, the -371AA genotype was associated with a significantly increased risk of squamous cell carcinoma compared to the combined -371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09-4.00, p = 0.03). The PAT-/+, IVS11-5C?A and Lys939Gln polymorphisms were associated with a significantly decreased risk of small cell carcinoma (SM) under a dominant model for the polymorphic allele (adjusted OR = 0.49, 95% CI 0.29-0.82, p = 0.006; adjusted OR = 0.60, 95% CI 0.36-1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35-0.97, p = 0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222) containing the PAT+/IVS11-5A/939Gln alleles was associated with a significantly decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37-0.85, p = 0.007 and Bonferroni-corrected p = 0.049), whereas haplotype 5 (1122111) containing the -27C allele was associated with a significantly increased risk of SM (adjusted OR = 2.88, 95% CI 1.41-5.87, p = 0.004 and Bonferronicorrected p = 0.028). These results suggest that XPC polymorphisms/haplotypes may contribute to genetic susceptibility for lung cancer. ' 2005 Wiley-Liss, Inc.

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Defective nucleotide excision repair in Xpc mutant mice and its association with cancer predisposition

Cited by 81 publications

References 33 publications

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

SNPs of Excision Repair Cross Complementing Group 5 and Gastric Cancer Risk in Chinese Populations

XPC polymorphisms and lung cancer risk

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