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Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans.

Publication ,  Journal Article
Walsh, KM; Amos, CI; Wenzlaff, AS; Gorlov, IP; Sison, JD; Wu, X; Spitz, MR; Hansen, HM; Lu, EY; Wei, C; Zhang, H; Chen, W; Lloyd, SM ...
Published in: Oncotarget
November 2012

Studies in European and East Asian populations have identified lung cancer susceptibility loci in nicotinic acetylcholine receptor (nAChR) genes on chromosome 15q25.1 which also appear to influence smoking behaviors. We sought to determine if genetic variation in nAChR genes influences lung cancer susceptibly in African-Americans, and evaluated the association of these cancer susceptibility loci with smoking behavior. A total of 1308 African-Americans with lung cancer and 1241 African-American controls from three centers were genotyped for 378 single nucleotide polymorphisms (SNPs) spanning the sixteen human nAChR genes. Associations between SNPs and the risk of lung cancer were estimated using logistic regression, adjusted for relevant covariates. Seven SNPs in three nAChR genes were significantly associated with lung cancer at a strict Bonferroni-corrected level, including a novel association on chromosome 2 near the promoter of CHRNA1 (rs3755486: OR = 1.40, 95% CI = 1.18-1.67, P = 1.0 x 10-4). Association analysis of an additional 305 imputed SNPs on 2q31.1 supported this association. Publicly available expression data demonstrated that the rs3755486 risk allele correlates with increased CHRNA1 gene expression. Additional SNP associations were observed on 15q25.1 in genes previously associated with lung cancer, including a missense variant in CHRNA5 (rs16969968: OR = 1.60, 95% CI = 1.27-2.01, P = 5.9 x 10-5). Risk alleles on 15q25.1 also correlated with an increased number of cigarettes smoked per day among the controls. These findings identify a novel lung cancer risk locus on 2q31.1 which correlates with CHRNA1 expression and replicate previous associations on 15q25.1 in African-Americans.

Duke Scholars

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

November 2012

Volume

3

Issue

11

Start / End Page

1428 / 1438

Location

United States

Related Subject Headings

  • Risk Factors
  • Receptors, Nicotinic
  • Polymorphism, Single Nucleotide
  • Male
  • Lung Neoplasms
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Walsh, K. M., Amos, C. I., Wenzlaff, A. S., Gorlov, I. P., Sison, J. D., Wu, X., … Wiencke, J. K. (2012). Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans. Oncotarget, 3(11), 1428–1438. https://doi.org/10.18632/oncotarget.746
Walsh, Kyle M., Christopher I. Amos, Angela S. Wenzlaff, Ivan P. Gorlov, Jennette D. Sison, Xifeng Wu, Margaret R. Spitz, et al. “Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans.Oncotarget 3, no. 11 (November 2012): 1428–38. https://doi.org/10.18632/oncotarget.746.
Walsh KM, Amos CI, Wenzlaff AS, Gorlov IP, Sison JD, Wu X, et al. Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans. Oncotarget. 2012 Nov;3(11):1428–38.
Walsh, Kyle M., et al. “Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans.Oncotarget, vol. 3, no. 11, Nov. 2012, pp. 1428–38. Pubmed, doi:10.18632/oncotarget.746.
Walsh KM, Amos CI, Wenzlaff AS, Gorlov IP, Sison JD, Wu X, Spitz MR, Hansen HM, Lu EY, Wei C, Zhang H, Chen W, Lloyd SM, Frazier ML, Bracci PM, Seldin MF, Wrensch MR, Schwartz AG, Wiencke JK. Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans. Oncotarget. 2012 Nov;3(11):1428–1438.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

November 2012

Volume

3

Issue

11

Start / End Page

1428 / 1438

Location

United States

Related Subject Headings

  • Risk Factors
  • Receptors, Nicotinic
  • Polymorphism, Single Nucleotide
  • Male
  • Lung Neoplasms
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female