Nicotinic acetylcholine receptor region on chromosome 15q25 and lung cancer risk among African Americans: a case-control study.
Genome-wide association studies of white persons with lung cancer have identified a region of extensive linkage disequilibrium on chromosome 15q25.1 that appears to be associated with both risk for lung cancer and smoking dependence. Because studying African American persons, who exhibit lower levels of linkage disequilibrium in this region, may identify additional loci that are associated with lung cancer, we genotyped 34 single-nucleotide polymorphisms (SNPs) in this region (including LOC123688, PSMA4, CHRNA5, CHRNA3, and CHRNB4 genes) in 467 African American patients with lung cancer and 388 frequency-matched African American control subjects. Associations of SNPs in LOC123688 (rs10519203; odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.25 to 2.05, P = .00016), CHRNA5 (rs2036527; OR = 1.67, 95% CI = 1.26 to 2.21, P = .00031), and CHRNA3 (rs1051730; OR = 1.81, 95% CI = 1.26 to 2.59, P = .00137) genes with lung cancer risk reached Bonferroni-corrected levels of statistical significance (all statistical tests were two-sided). Joint logistic regression analysis showed that rs684513 (OR = 0.47, 95% CI = 0.31 to 0.71, P = .0003) in CHRNA5 and rs8034191 (OR = 1.76, 95% CI = 1.23 to 2.52, P = .002) in LOC123688 were also associated with risk. The functional A variant of rs1696698 in CHRNA5 had the strongest association with lung cancer (OR = 1.98, 95% CI = 1.25 to 3.11, P = .003). These SNPs were primarily associated with increased risk for lung adenocarcinoma histology and were only weakly associated with smoking phenotypes. Thus, among African American persons, multiple loci in the region of chromosome 15q25.1 appear to be strongly associated with lung cancer risk.
Amos
Christopher I
CI
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. camos@mdanderson.org
Gorlov
Ivan P
IP
Dong
Qiong
Q
Wu
Xifeng
X
Zhang
Huifeng
H
Lu
Emily Y
EY
Scheet
Paul
P
Greisinger
Anthony J
AJ
Mills
Gordon B
GB
Spitz
Margaret R
MR
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013781:Texas / Q000453:epidemiology
D009419:Nerve Tissue Proteins; D046988:Proteasome Endopeptidase Complex; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human