Estimates of risk associated with these three SNPs are consistent with the GWAS results6–8 and with the existence of a gene associated with lung cancer, directly or indirectly through nicotine dependence, on chromosome 15q25. Among white cases in our studies, all three SNPs were significantly related to smoking amount measured as cigarettes smoked per day and may contribute to lung cancer risk through increased exposure to tobacco smoke. Risk associated with these SNPs is highest in ever smoking whites after adjustment for cigarettes per day for rs931794, but these findings did not reach statistical significance. Amos et al.6 also report weak evidence of a relationship between genotype and smoking behavior and there is extensive literature indicating that SNPs in this region associate with smoking behavior8,17. It is possible that this study was underpowered to detect a small increase in lung cancer risk, on the order of 10–15%, independent of smoking quantity in whites.
