Carcinogenesis Advance Access originally published online on November 24, 2008
Carcinogenesis 2009 30(1):78-87; doi:10.1093/carcin/bgn261
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Base excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African-Americans
Department of Epidemiology and Biostatistics
1 Department of Neurological Surgery, Division of Neuroepidemiology, University of California, San Francisco, San Francisco, CA 94143-1215, USA
2 Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-2911, USA
3 Division of Research, Kaiser Permanente, Oakland, CA 94612, USA
4 Rowe Program in Human Genetics, Departments of Biological Chemistry and Medicine, University of California, Davis, Davis, CA 95616-8500, USA
5 Center for Environmental Health and Technology, Department of Community Medicine and Pathology and Laboratory Medicine, Brown University, Providence, RI 02912, USA
* To whom correspondence should be addressed. 44 Page Street, suite 503, University of California, San Francisco, San Francisco, CA 94143-1215, USA. Tel: +1 510 642 6299; Fax: +1 415 502 1787; Email: jeffrey.chang{at}ucsf.edu
Base excision repair (BER) is the primary DNA damage repair mechanism for repairing small base lesions resulting from oxidation and alkylation damage. This study examines the association between 24 single-nucleotide polymorphisms (SNPs) belonging to five BER genes (XRCC1, APEX1, PARP1, MUTYH and OGG1) and lung cancer among Latinos (113 cases and 299 controls) and African-Americans (255 cases and 280 controls). The goal was to evaluate the differences in genetic contribution to lung cancer risk by ethnic groups. Analyses of individual SNPs and haplotypes were performed using unconditional logistic regressions adjusted for age, sex and genetic ancestry. Four SNPs among Latinos and one SNP among African-Americans were significantly (P < 0.05) associated with either risk of all lung cancer or non-small cell lung cancer (NSCLC). However, only the association between XRCC1 Arg399Gln (rs25487) and NSCLC among Latinos (odds ratio associated with every copy of Gln = 1.52; 95% confidence interval: 1.01–2.28) had a false-positive report probability of <0.5. Arg399Gln is a SNP with some functional evidence and has been shown previously to be an important SNP associated with lung cancer, mostly for Asians. Since the analyses were adjusted for genetic ancestry, the observed association between Arg399Gln and NSCLC among Latinos is unlikely to be confounded by population stratification; however, this result needs to be confirmed by additional studies among the Latino population. This study suggests that there are genetic differences in the association between BER pathway and lung cancer between Latinos and African-Americans.
Abbreviations: BER, base excision repair; FPRP, false-positive report probability; NSCLC, non-small cell lung cancer; OR, odds ratio; PCA, principal components analysis; SNP, single-nucleotide polymorphism
Received July 14, 2008; revised November 17, 2008; accepted November 18, 2008.