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: 6.2). 12/2008; 123(9):2095-104. DOI: 10.1002/ijc.23801
Source: PubMed

ABSTRACT 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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    ABSTRACT: The xeroderma pigmentosum complementation group G (XPG) gene plays an important role in the DNA nucleotide excision repair (NER) pathway. Several studies have investigated the association between the XPG Asp1104His polymorphism and breast cancer; however, the results have been inconsistent. Therefore, we conducted a meta-analysis of 8 published articles (10 case-control studies) including a total of 5,235 patients with breast cancer and 5,685 healthy controls. The results demonstrated that the XPG Asp1104His polymorphism was not associated with breast cancer in the overall population [His vs. Asp, odds ratio (OR)=1.00, 95% confidence interval (CI): 0.91-1.08; His/His vs. Asp/Asp, OR=0.96, 95% CI: 0.83-1.11; Asp/His vs. Asp/Asp, OR=1.02, 95% CI: 0.94-1.11; His/His+Asp/His vs. Asp/Asp, OR=1.03, 95% CI: 0.92-1.15; and His/His vs. Asp/Asp+Asp/His, OR=0.93, 95% CI: 0.81-1.06]. In the subgroup analysis by ethnicity, no significant association was observed in European subjects. In conclusion, this meta-analysis suggested that the XPG Asp1104His polymorphism is not associated with breast cancer risk.
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