In addition to previous associations with nicotine dependence (7, 8) and heavy smoking (6), two of the SNPs in the CHRNA5-CHRNA3-CHRNB4 gene cluster (rs8034191 and rs1051730) have been found to be associated with lung cancer risk (11, 12). In our analysis, the association of these SNPs with heavy smoking was unchanged when individuals with lung cancer were excluded, suggesting that the significant variants we observed predict for heavy smoking, regardless of whether they predict for lung cancer. While we did find that the homozygous variant genotype of the risk SNPs was significantly associated with increased risk of lung cancer, this finding could be due to chance; it was based on a small numbers of lung cancer cases, and the OR was less than 1.0 in the heterozygous variant.
