Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African-Americans

Helen M. Hansen, Yuanyuan Xiao, Terri Rice, Paige M. Bracci, Margaret R. Wrensch, Jennette D. Sison, Jeffery S. Chang, Ivan V. Smirnov, Joseph Patoka, Michael F Seldin, Charles P. Quesenberry, Karl T. Kelsey, John K. Wiencke

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Several genome-wide association studies identified the chr15q25.1 region, which includes three nicotinic cholinergic receptor genes (CHRNA5-B4) and the cell proliferation gene (PSMA4), for its association with lung cancer risk in Caucasians. A haplotype and its tagging single nucleotide polymorphisms (SNPs) encompassing six genes from IREB2 to CHRNB4 were most strongly associated with lung cancer risk (OR = 1.3; P < 10-20). In order to narrow the region of association and identify potential causal variations, we performed a fine-mapping study using 77 SNPs in a 194 kb segment of the 15q25.1 region in a sample of 448 African-American lung cancer cases and 611 controls. Four regions, two SNPs and two distinct haplotypes from sliding window analyses, were associated with lung cancer. CHRNA5 rs17486278 G had OR = 1.28, 95% CI 1.07-1.54 and P = 0.008, whereas CHRNB4 rs7178270 G had OR = 0.78, 95% CI 0.66-0.94 and P = 0.008 for lung cancer risk. Lung cancer associations remained significant after pack-year adjustment. Rs7178270 decreased lung cancer risk in women but not in men; gender interaction P = 0.009. For two SNPs (rs7168796 A/G and rs7164594 A/G) upstream of PSMA4, lung cancer risks for people with haplotypes GG and AA were reduced compared with those with AG (OR = 0.56, 95% CI 0.38-0.82; P = 0.003 and OR = 0.73, 95% CI 0.59-0.90, P = 0.004, respectively). A four-SNP haplotype spanning CHRNA5 (rs11637635 C, rs17408276 T, rs16969968 G) and CHRNA3 (rs578776 G) was associated with increased lung cancer risk (P = 0.002). The identified regions contain SNPs predicted to affect gene regulation. There are multiple lung cancer risk loci in the 15q25.1 region in African-Americans.

Original languageEnglish (US)
Article numberddq268
Pages (from-to)3652-3661
Number of pages10
JournalHuman Molecular Genetics
Volume19
Issue number18
DOIs
StatePublished - Jun 29 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Fingerprint Dive into the research topics of 'Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African-Americans'. Together they form a unique fingerprint.

  • Cite this

    Hansen, H. M., Xiao, Y., Rice, T., Bracci, P. M., Wrensch, M. R., Sison, J. D., Chang, J. S., Smirnov, I. V., Patoka, J., Seldin, M. F., Quesenberry, C. P., Kelsey, K. T., & Wiencke, J. K. (2010). Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African-Americans. Human Molecular Genetics, 19(18), 3652-3661. [ddq268]. https://doi.org/10.1093/hmg/ddq268