Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
International Journal of Cancer (Impact Factor: 5.09). 11/2008; 123(9):2095-104. DOI: 10.1002/ijc.23801
Source: PubMed


Few studies on the association between nucleotide excision repair (NER) variants and lung cancer risk have included Latinos and African Americans. We examine variants in 6 NER genes (ERCC2, ERCC4, ERCC5, LIG1, RAD23B and XPC) in association with primary lung cancer risk among 113 Latino and 255 African American subjects newly diagnosed with primary lung cancer from 1998 to 2003 in the San Francisco Bay Area and 579 healthy controls (299 Latinos and 280 African Americans). Individual single nucleotide polymorphism and haplotype analyses, multifactor dimensionality reduction (MDR) and principal components analysis (PCA) were performed to assess the association between 6 genes in the NER pathway and lung cancer risk. Among Latinos, ERCC2 haplotype CGA (rs238406, rs11878644, rs6966) was associated with reduced lung cancer risk [odds ratio (OR) of 0.65 and 95% confidence interval (CI): 0.44-0.97], especially among nonsmokers (OR = 0.29; 95% CI: 0.12-0.67). From MDR analysis, in Latinos, smoking and 3 SNPs (ERCC2 rs171140, ERCC5 rs17655 and LIG1 rs20581) together had a prediction accuracy of 67.4% (p = 0.001) for lung cancer. Among African Americans, His/His genotype of ERCC5 His1104Asp (rs17655) was associated with increased lung cancer risk (OR = 1.78; 95% CI: 1.09-2.91), and LIG1 haplotype GGGAA (rs20581, rs156641, rs3730931, rs20579 and rs439132) was associated with reduced lung cancer risk (OR = 0.61; 95% CI: 0.42-0.88). Our study suggests different elements of the NER pathway may be important in the different ethnic groups resulting either from different linkage relationship, genetic backgrounds and/or exposure histories.

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Available from: Melinda C Aldrich
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    • "contains 11 exons and spans approximately 28.2 kb, and plays a key role in the 5' incision made in the NER pathway, and function as removing DNA interstrand crosslinks and DNA double-strand breaks (Mueser et al., 1996; Friedberg et al., 2000). It is reported that polymorphisms in several SNPs of XPF alter genetic susceptibility to cancer, such as colorectal cancer, breast cancer, lung cancer and prostate cancer as well (Crew et al., 2007; Chang et al., 2008; Agalliu et al., 2010; Gil et al., 2011). However, there is still no evidence on the association between XPF polymorphisms and gastric cancer risk in Chinese 1848 population (He et al., 2012). "
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    ABSTRACT: We conducted a hospital case-control study by genotyping four potential functional single nucleotide polymorphisms (SNPs) to assess the association of Xeroderma pigmentosum complementation group F (XPF) with gastric cancer susceptibility, and role of XPF polymorphisms in combination with H.pylori infection in risk definition. A total of 331 patients with gastric cancer and 355 controls were collected. Four SNPs of XPF, rs180067, rs1799801, rs2276466 and rs744154, were genotyped by Taqman real-time PCR method with a 7900 HT sequence detector system. The gastric cancer patients were more likely to have smoking habit, a family history of cancer and H.pylori infection. We did not find any significant difference in the genotype distributions of XPF rs180067, rs1799801, rs2276466 and rs744154 between cases and controls. However, multivariate logistic analysis showed a non-significant decreased risk in patients carrying rs180067 G allele, rs1799801 T allele or rs2276466 T allele genotypes. A non-significant increased risk of gastric cancer was found in individuals carrying the rs744154 GG genotype. Stratification by H.pylori infection and smoking was not significantly different in polymorphisms of XPF rs180067, rs1799801, rs2276466 and rs744154. The four XPF SNPs did not show significant interaction with H.pylori infection and smoking status (P for interaction was 0.35 and 0.18, respectively). Our study indicated that polymorphisms in rs180067, rs1799801, rs2276466 and rs744154 may affect the risk of gastric cancer but further large sample size studies are needed to validate any association.
    Preview · Article · Mar 2013 · Asian Pacific journal of cancer prevention: APJCP
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    • "This protein combined with ERCC1 is involved in a dual incision at both the 3' and 5' sites of the lesion, and produces the excision of damage-containing oligomers of 22-32 nucleotides in length (Friedberg, 2003). Currently, various epidemiological studies suggested that defective XPG gene polymorphisms have a vital role in the development of various cancers, such as lung, esophageal, colorectal cancer, bladder, ovarian and gastric cancer (Nouspikel et al., 1997; Chang et al., 2008; Bartolucci et al., 2009; Sun et al., 2009; Sakano et al., 2010; Fleming et al., 2012; He et al., 2012). However, only three studies with small sample "
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    ABSTRACT: Polymorphisms in XPG are considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We aimed to investigate the role of five potential SNPs of XPG gene on the response to platinum-based chemotherapy in advanced Chinese NSCLC patients. A total of 451 patients with newly diagnosed and histopathologically confirmed primary NSCLC were consecutively collected. XPG rs2296147, rs4150261, rs17655, rs1047768 and rs2094258 were genotyped by the Taqman real-time polymerase chain reaction (PCR). In our study, we found patients carrying rs1057768 TT genotype had a significantly lower treatment response when compared with the CC genotype (OR=0.38, 95% CI=0.18-0.78). Patients carrying rs1047768 TT genotype showed a significantly short median PFS (11.2 months) and OS (13.6 months) than CC genotype, and the hazard ratios (HR) for PFS and OS were 2.06 (1.01-4.50) and 2.29 (1.21-2.49), respectively. Moreover, we found a significant decreased risk of death from NSCLC among patients carrying the rs2296147 TT genotype when compared with the CC genotype, the HR (95% CI) for OS being 0.50 (0.27-0.95). In conclusion, our study found that polymorphisms in rs1047768 C/T and rs2296147 C/T are associated with response to platinum-based chemotherapy in advanced NSCLC, and XPG polymorphisms could be predictive of prognosis.
    Preview · Article · Feb 2013 · Asian Pacific journal of cancer prevention: APJCP
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    • "To date, most studies have investigated the association between the XPG His1104Asp (rs17655) polymorphism and cancer risk. In a Korean case–control study of 310 lung cancer patients and 311 healthy controls, the Asp/Asp genotype was associated with a significantly decreased risk of lung cancer when the combined His/His and His/Asp genotype was used as the reference (Jeon et al. 2003); among 255 lung cancer and 280 controls from African Americans, the His/His genotype was associated with an increased lung cancer risk (Chang et al. 2008); however, no significant difference was found in a population-based case–control study of 122 cases and 122 controls in the highest lung cancer incident area, Xuan Wei, China (Shen et al. 2005). Furthermore, in a hospital-based case–control study of 829 SCCHN cases and 854 cancer-free controls, no significant difference was found among the three genotypes of the XPG His1104Asp polymorphism (An et al. 2007). "
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    ABSTRACT: DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case–control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03–1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01–1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P trend = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P trend = 0.003) as well as for 261 subjects with different ethnicities (P trend = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.
    Full-text · Article · Feb 2012 · Human Genetics
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