Tobacco smoke, laden with carcinogens like benzopyrene, nitrosamines, and reactive oxygen species (ROS), induces genetic mutations and impairs DNA repair by downregulating tumor suppressor genes like tumor protein 53 (P53), ataxia-telangiectasia mutated (ATM), ataxia telangiectasia and Rad3-related (ATR), and poly (ADP-ribose) polymerase 1 (PARP1), leading to genomic instability and heightened cancer risk. The gene discussed is ATM; the disease is cancer.