The Arg280His polymorphism in X-ray repair cross-complementing gene 1 impairs DNA repair ability

Takanami, Takako; Nakamura, Jun; Kubota, Yukiho; Horiuchi, Saburo

doi:10.1016/j.mrgentox.2005.01.007

Cited by 83 publications

(65 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we reported an XRCC1 genotype Â smoking interaction effect on risk of colorectal adenomas in a Los Angeles sigmoidoscopybased study; the smoking effect was noted only among carriers of the Arg 194 -Arg 399 haplotype (41). Phenotype association studies suggest that both the XRCC1 codon 194 Trp and codon 399 Arg alleles are associated with higher repair proficiency (40), although functional studies have failed to find an effect for either SNP (42,43). Interestingly, a functional effect was reported for the codon 280 SNP (42), which is in LD with the codons 194 and 399 SNPs.…”

Section: Discussionmentioning

confidence: 99%

DNA Repair Single-Nucleotide Polymorphisms in Colorectal Cancer and their Role as Modifiers of the Effect of Cigarette Smoking and Alcohol in the Singapore Chinese Health Study

Stern

Conti

Siegmund

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Recently, we reported that among Singapore Chinese, cigarette smoking and alcohol drinking were independent risk factors for colorectal cancer. Both tobacco smoking and alcohol use are plausible colorectal cancer risk factors, partly due to their ability to induce mutations in the colorectal lumen. . We conducted this study within the Singapore Chinese Health Study, a population-based cohort of 63,257 middle-aged and older Singapore Chinese men and women enrolled between 1993 and 1998. Our study included 1,176 controls and 310 cases (180 colon and 130 rectum cancer). We observed a positive association between the PARP codon 940 Lys/Arg and Arg/Arg genotypes and colorectal cancer risk [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 1.1-3.1], and an inverse association between the MGMT codon 84 Leu/Phe or Phe/Phe genotypes and colon cancer risk (OR, 0.6; 95% CI, 0.3-0.9), but not rectal cancer (test of heterogeneity by tumor site, P = 0.027). We observed evidence that XRCC1 may modify the effects of smoking (interaction P = 0.012). The effect of smoking among carriers of the Arg 194 -Gln 399 haplotype was OR = 0.7 (95% CI, 0.4-1.1), whereas, among carriers of the Trp 194 -Arg 399 haplotype, it was OR = 1.6 (95% CI, 1.1-2.5). We also observed a nonstatistically significant modification of XRCC1 on the effects of alcohol (P = 0.245). Whereas alcohol had no effect among carriers of the codon 194 Arg/Arg (OR, 1.0; 95% CI, 0.6-1.7) or Arg/Trp genotypes (OR, 1.1; 95% CI, 0.6-1.9), there was a positive association among carriers of the Trp/Trp genotype (OR, 2.8; 95% CI, 1.0-8.1). Our results support a role for reactive oxygen species as relevant genotoxins that may account for the effects of both smoking and alcohol on colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2363 -72)

show abstract

Section: Discussionmentioning

confidence: 99%

DNA Repair Single-Nucleotide Polymorphisms in Colorectal Cancer and their Role as Modifiers of the Effect of Cigarette Smoking and Alcohol in the Singapore Chinese Health Study

Stern

Conti

Siegmund

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…MMS is an alkylating chemical that generates SSB in DNA, which require XRCC1 for efficient repair. The results by Takanami et al (2005) suggest that the function of XRCC1 may be compromised by the histidine allele. By using the comet assay, they showed that there was a significant delay in SSB repair at 60 min in CHO cells with the histidine genotype compared to CHO cells with the arginine genotype.…”

Section: R280hmentioning

confidence: 96%

“…EM9 is thus a null mutant with genetic characteristics comparable to mouse cells carrying a knockout mutation. Takanami et al (2005) made plasmid constructs expressing XRCC1 wild-type, R194W or R280H and transfected them into EM9 CHO cells. These cells were then exposed to MMS and assayed for survival.…”

Section: Xrcc1 Polymorphisms and Cancer Association Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Mouse models of XRCC1 DNA repair polymorphisms and cancer

Ladiges

2006

Oncogene

View full text Add to dashboard Cite

DNA damage plays a major role in mutagenesis, carcinogenesis and aging. A gene that is emerging as an essential element in the repair of both damaged bases and single-strand breaks (SSB) is XRCC1. XRCC1 has been shown to have a large number of single-nucleotide polymorphisms (SNPs), several of which are being increasingly studied in cancer epidemiology investigations, in part because of their relative high frequency in the population. Although association trends with specific cancer types have occasionally been shown in a variety of ethnic backgrounds, there are often conflicting reports that weaken any substantial conclusions. The functional significance of these SNPs is still largely unknown. XRCC1 is an excellent prototype to provide a forum for determining how epidemiological cancer association studies with DNA repair gene polymorphisms can be validated or refuted. The focus is on the utilization of in silico data and biochemical studies in cell lines and existing mouse models to help provide a framework for the development of new mutant mouse lines that mimic human polymorphisms. These mouse lines will provide the next generation of mammalian tools for carcinogen exposure studies relevant to human cancer and variations in XRCC1, and provide the basis for investigating groups of genes and polymorphisms in an animal model.

show abstract

“…Moreover, there is evidence that SNP which occurred in the exon of DNA repair pathway genes could modify DNA repair capability, even susceptibility to cancers (Takanami et al, 2005). XRCC3 belongs to DNA double-strand break repair pathway.…”

Section: Discussionmentioning

confidence: 99%

The XRCC3 Thr241Met Polymorphism Influences Glioma Risk - A Meta-analysis

Jiang

Quan²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Findings from previous published studies regarding the association of the XRCC3 Thr241Met polymorphism with glioma susceptibility have often been conflicting. Therefore, a meta-analysis including all available publications was carried out to make a more precise estimation of the potential relationship. Methods: By searching the electronic databases of Pubmed and Embase (up to April 1st, 2013), a total of nine case-control studies with 3,752 cases and 4,849 controls could be identified for inclusion in the current meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. Results: This meta-analysis showed the XRCC3 Thr241Met polymorphism to be significantly associated with decreased glioma risk in the allelic model (Met allele vs. Thr allele: OR= 0.708, 95%CI= 0.631-0.795). Moreover, we also observed a statistically significant association between the XRCC3 Thr241Met polymorphism and reduced glioma risk in analyses stratified by ethnicity (Asian) and source of controls (hospital based) in the allelic model. Conclusions: Current evidence suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for glioma development, especially in Asians.

show abstract

The Arg280His polymorphism in X-ray repair cross-complementing gene 1 impairs DNA repair ability

Cited by 83 publications

References 35 publications

DNA Repair Single-Nucleotide Polymorphisms in Colorectal Cancer and their Role as Modifiers of the Effect of Cigarette Smoking and Alcohol in the Singapore Chinese Health Study

DNA Repair Single-Nucleotide Polymorphisms in Colorectal Cancer and their Role as Modifiers of the Effect of Cigarette Smoking and Alcohol in the Singapore Chinese Health Study

Mouse models of XRCC1 DNA repair polymorphisms and cancer

The XRCC3 Thr241Met Polymorphism Influences Glioma Risk - A Meta-analysis

Contact Info

Product

Resources

About