In accord with the findings of multiple GWAS which indicate that SNPs of the gene cluster 15q25, which contains CHRNA3, CHRNA5, CHRNB4, are associated with increased risks of lung cancer and COPD as well as nicotine-dependence, recent cellular and molecular studies on nAChRs indicate that chronic exposure to nicotine or nicotine-derived carcinogenic nitrosamines upregulates the α7-nAChR and α9-nAChR and desensitizes the heteromeric α4β2-nAChR to activate the oncogenic pathways, promotes tumor angiogenesis, and inhibits drug induced apoptosis in multiple types of cancers. The gene discussed is CHRNA5; the disease is nicotine dependence.