Two of the correlated SNPs we found associated with increased risk of heavy smoking (rs803191 and rs1051730) have also been found to be associated with increased risk of lung cancer by three large GWASs (10, 11, 12). In our study, 10 light smokers and 75 heavy smokers had been diagnosed with incident lung cancer. To determine if any part of the association we observed between these SNPs and heavy smokers was due to a direct association of the SNPs with lung cancer, we conducted a sensitivity analysis excluding the 85 lung cancer cases. The associations of both the risk and protective SNPs with heavy smoking changed very little (≤0.01 for per-allele and ≤0.02 for genotype ORs). As reflected in the trend p-values, which are listed in the column labeled excluded LCa p in Table 2, all previously significant results remained significant. The p-values for the risk SNPs (dark rows) were slightly attenuated while those for the protective SNPs (gray rows) were somewhat more significant.
