Huang WY, Berndt SI, Kang D et al.Nucleotide excision repair gene polymorphisms and risk of advanced colorectal adenoma: XPC polymorphisms modify smoking-related risk. Cancer Epidemiol Biomarkers Prev 15:306-311

Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 03/2006; 15(2):306-11. DOI: 10.1158/1055-9965.EPI-05-0751
Source: PubMed


Nucleotide excision repair enzymes remove bulky damage caused by environmental agents, including carcinogenic polycyclic aromatic hydrocarbons found in cigarette smoke, a risk factor for colorectal adenoma. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we studied the risk of advanced colorectal adenoma in relation to cigarette smoking and selected single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway.
Cases (n = 772) were subjects with left-sided advanced adenoma (>1 cm in size, high-grade dysplasia, or villous characteristics). Controls (n = 777) were screen-negative for left-sided polyps by sigmoidoscopy. DNA was extracted from blood samples and 15 common nonsynonymous SNPs in seven-nucleotide excision repair genes [XPC, RAD23B (hHR23B), CSB (ERCC6), XPD (ERCC2), CCNH, XPF (ERCC4), and XPG (ERCC5)] were genotyped.
None of the studied SNPs were independently associated with advanced adenoma risk. Smoking was related to adenoma risk and XPC polymorphisms (R492H, A499V, K939Q) modified these effects (P(interaction) from 0.03-0.003). Although the three XPC variants were in linkage disequilibrium, a multivariate logistic regression tended to show independent protective effects for XPC 499V (P(trend) = 0.06), a finding supported by haplotype analysis (covariate-adjusted global permutation P = 0.03).
Examining a spectrum of polymorphic variants in nucleotide excision repair genes, we found evidence that smoking-associated risks for advanced colorectal adenoma are modified by polymorphisms in XPC, particularly haplotypes containing XPC 499V.

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    • "Thus, our study found that the presence of at least one Gln751 allele could influence the risk of sporadic colorectal cancer in both smoker females and males. The results were in accordance with those obtained byBigler et al (2005), but not with those obtained byHuang et al (2006) andStern et al (2006) (22, 23, 25). We found a stronger association between a diet rich in fried red meat intake and colorectal cancer risk in both females and males, independently of the Gln751-XPD allele. "
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    ABSTRACT: Background: Genetic variations, such as those affecting DNA repair genes, could represent susceptibility factors for sporadic colorectal cancer (CRC) as a result of their interaction with environmental factors. Materials and methods: 80 female and 70 males patients diagnosed with sporadic CRC in the Surgical Clinic III Cluj were geno-typed for Arg399Gln-XRCC1, Lys751Gln-XPD and Met241Thr-XRCC3 using PCR-RFLP methods. We also geno-typed 100 females and 62 males, who formed the control group. Genotyping results were related to environmental risk factors, smoking habit and diet. Results: Male patients carriers of the Arg399Gln, Lys751Gln, Met241Thr had a 4.09 (95%CI[0.96-19.98],p=0.05)-fold, 5.95(95%CI[1.08-43.22],p=0.03)-fold and 3.73(95%CI[0.86-18.53],p=0.05)- fold significantly increased risk to develop sporadic CRC if they smoked. A significantly increased risk for CRC was observed in females and males with high daily fried red meat intake, carriers of the Arg399Gln (OR 2.77 95%CI [1.34-6.82],p=0.015 and OR 8.64 95%CI[2.67-29.14],p<0.001), Lys751Gln (OR 4.12 95%CI[1.37-12.74],p=0.007 and OR 5.06 95%CI[1.4-19.02],p=0.006), Met241Thr (OR5.92 95%CI[2.21-16.23],p<0.001 and OR 5.64 95%CI[1.52-21.7],p=0.022). Female patients with high fried red meat intake had a significantly higher risk to develop early-onset sporadic CRC if they were carriers of the Arg399Gln-XRCC1 (OR 5.14 95%CI[0.99-28.3],p=0.047), Thr241Met-XRCC3 (OR 6.67 95%CI[1.05-46.67],p=0.025) and Lys-751Gln-XPD (OR 4.7 95%CI[0.99-23.32],p=0.034). Conclusions: In Romanians, the association between the mutated genotypes and environmental risk factors modulates the risk for sporadic CRC. Smoking in association with the Arg399Gln-XRCC1 genetic variation influences the early onset of sporadic colorectal cancer in females. Diet rich in fried red meat intake associated with Arg399Gln-XRCC1, Lys751Gln-XPD and Thr241Met- XRCC3 genetic variations significantly influences the early onset of sporadic colorectal cancer in females.
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    • "Subsequently, disruption of this gene was related to the development of age-related macular degeneration (Tuo et al., 2006). Quite recently, genetic variations of ERCC6 have been linked to the susceptibility to various cancers, including lung cancer (Lin et al., 2008; Ma et al., 2009), breast cancer (Mechanic et al., 2006; Rajaraman et al., 2008), prostate cancer (Hooker et al., 2008), bladder cancer (Chen et al., 2007; Chang et al., 2009) and colorectal cancer (Berndt et al., 2006; Huang et al., 2006). However, the relation of ERCC6 polymorphism with gastric cancer risk is still unclear, which deserves to be further clarified. "
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    ABSTRACT: Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotide excision repair pathway that plays an important role in maintaining genomic stability and integrity. Several recent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, the relation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age- matched case-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the association between a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk. Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status of Helicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95% confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the common TT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46, 95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrated a statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was also observed for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs. T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to be enhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reach statistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GC risk in Chinese, especially in males.
    Preview · Article · Oct 2013 · Asian Pacific journal of cancer prevention: APJCP
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    • "Up to now, a total of 580 single nucleotide polymorphisms (SNPs) in the XPF gene have been reported according to the dbSNP database (, some of which have been reported to be associated with risk of several kinds of cancers, such as breast cancer, endometrial cancer, colorectal cancer, head and neck cancer, lung cancer and skin cancers (Huang et al., 2006; Han et al., 2009; Doherty et al., 2011). However, only one study explores the role of two SNPs of ERCC4 in the risk of glioma in USA, so we reported the predictive role of four XPF SNPs in the risk of glioma. "
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    ABSTRACT: We conducted an exploratory investigation of whether variation in six common SNPs of xeroderma pigmentosum complementation group F (XPF) is associated with risk of glioma in a Chinese population. Six single nucleotide polymorphisms (SNPs) were genotyped in 207 glioma cases and 236 cancer-free controls by a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, USA). The rs1800067 G and rs2276466 G allele frequencies were significantly higher in the glioma group than controls. Individuals with the rs1800067 GG genotype were at greater risk of glioma when compared with the A/A genotype in the codominant model, with an OR (95% CI) of 2.63 (1.04-7.25). The rs2276466 polymorphism was significantly associated with moderate increased risk of glioma in codominant and dominant models, with ORs (95% CI) of 1.90 (1.05-3.44) and 1.55 (1.07-2.47), respectively. The combination genotype of rs1800067 G and rs2276466 G alleles was associated with a reduced risk of glioma (OR=0.44, 95% CI=0.19-0.98). These findings indicate that genetic variants of the XPF gene have critical functions in the development of glioma.
    Preview · Article · Jul 2013 · Asian Pacific journal of cancer prevention: APJCP
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