Lung cancer is the leading cause of cancer death in the U.S and is approximately 30% higher in African‐Americans than in Caucasians. Recently, several groups including ours, using genome‐wide association study, identified and replicated a region of chromosome 15q24–25.1 that had a highly reliable and significant association with lung cancer risk. Analysis of SNPs in this region identified association with variability in expression of exons 3–5 of CHRNA5. To identify additional variation that may be associated with lung cancer risk we started to re‐sequence all of the exons and surrounding intron/exon boundaries for the genes in the region including CHRNA3, CHRNA5, PSMA4 and LOC123688, in 46 lung cancer cases and 46 control. Among these 4 genes, the first two are nicotinic acetylcholine receptor. Results of sequencing identified many new variants, and there were significantly more rare variants in cases than controls for CHRNA5. We evaluated 6 of these rare variants, located within the region of exon3–5 of CHRNA5 that were identified by resequencing, in a case controls study of African America population. However none of these 6 novel variants we identified were significantly more common in 467 cases than in 388 controls. In addition to these rare variants, we identified insertion/deletion variations in the promoters region of CHRNA5 and we will evaluate the association of these insertion/deletion variations with lung cancer in a large sample size of African America population. Taken together, the finding provides additional information on the association of nicotinic acetylcholine receptor region on chromosome 15q25 and lung cancer risk.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A125.