Article

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.

0 Bookmarks
 · 
155 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Although numerous studies have investigated the association between DNA repair gene variants and lung cancer risk, the results remain inconclusive and incomplete.Methods We examined variants in seven nucleotide excision repair (NER) and RRM1 genes in association with primary lung cancer risk among 385 patients with newly diagnosed primary non-small cell lung cancer and 208 cancer-free controls collected from 2007 to 2009 in east China. The relationship between single nucleotide polymorphisms and risk of lung cancer was assessed by logistic regression and stratification analysis.Results The rs17655GG (ERCC5) and rs5744751CT (POLE) were associated with increased risk of lung cancer (adjusted odds ratio [OR], 2.32, 95% confidence interval [CI], 1.41–3.83; adjusted OR, 2.84, 95% CI, 1.70–4.74]. In stratification analysis, we found the increased effect of rs17655GG on the risk of lung cancer was observed among female, older subjects, or non-smokers. The heterozygote computed tomography (CT) of rs5744751 had a stronger unprotective effect on lung cancer among male, older subjects, or heavy smokers.Conclusion These results suggest that rs17655GG and rs5744751CT may be associated with lung cancer susceptibility in the Chinese population. However, these findings still need to be verified in larger confirmatory studies.
    Thoracic Cancer. 08/2012; 3(3).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Xeroderma pigmentosum group D (XPD) rs13181 may reduce DNA repair capacity (DRC) through modifying XPD protein product. Reduced DRC is reportedly related to an increase in the risk of lung cancer. To precisely estimate the association between XPD rs13181 and lung cancer risk, we carried out the current meta-analysis. We searched multiple databases (up to 31 October 2013) for studies investigating the association of XPD rs13181 and lung cancer. Odds ratio (OR) was estimated with the fixed effect model to assess the association. Heterogeneity between studies was measured using Q test. Subgroup analyses were conducted by ethnicity, histological type, and sample size. Meta-analysis of 30 studies suggested that individuals carrying Gln/Gln genotype were more likely than the individuals with Lys/Lys or Lys/Gln + Lys/Lys genotypes (homozygous model, OR 1.18, 95 % confidence interval (CI) 1.07-1.31; recessive model, OR 1.17, 95 % CI 1.06-1.29) to develop lung cancer, without any substantial heterogeneity. This significantly increased risk was also revealed in the individuals harboring Gln/Gln + Lys/Gln genotypes (dominant model, OR 1.07, 95 % CI 1.01-1.12). Further stratification by histological type, ethnicity, and sample size yielded statistically significant estimates in subgroup of Caucasian subjects, non-small cell lung cancer, and relatively large studies, but borderline association in Asians. Our analyses demonstrate that XPD rs13181 may be associated with an increase in the risk of lung cancer among Caucasian populations.
    Tumor Biology 05/2014; 35(8). · 2.84 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Molecular and Clinical Oncology 11/2014; 2(6):1177-1181.

Full-text (2 Sources)

Download
39 Downloads
Available from
Jun 3, 2014