Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans.
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.
Chang
Jeffrey S
JS
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. jeffrey.chang@ucsf.edu
Wrensch
Margaret R
MR
Hansen
Helen M
HM
Sison
Jennette D
JD
Aldrich
Melinda C
MC
Quesenberry
Charles P
CP
Seldin
Michael F
MF
Kelsey
Karl T
KT
Kittles
Rick A
RA
Silva
Gabriel
G
Wiencke
John K
JK
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012306:Risk; D012907:Smoking / Q000009:adverse effects; D014157:Transcription Factors / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
D000072481:DNA Ligase ATP; D011088:DNA Ligases; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C000607892:LIG1 protein, human; C497292:ERCC2 protein, human