Cigarette smoking is the leading cause of lung cancer, accounting for about 85% of lung cancers. Risk for lung cancer increases with the duration, intensity and depth of smoke inhalation.
Second-hand (passive) smoking also causes lung cancer, but is less strongly associated compared to active smoking.
Cigarettes contain multiple carcinogens (more than 60) that have been shown to induce cancers in laboratory settings.
J Natl Cancer Inst. 2004 Jan 21;96(2):99-106.
Polycyclic aromatic hydrocarbons (PAH) such as benzo[α]pyrene produce mutations in the p53 gene. G to T transversion within the p53 gene is a molecular signature of lung tumours caused by tobacco mutagens.
N-nitroso compounds are a major group of chemicals found in tobacco smoke, several of which are potent animal carcinogens.
Nicotine: causes addiction to cigarette smoking and is also a promoter for carcinogenesis.
Sympathetic/parasympathetic activation: nicotine binds to and activates nicotinic cholinergic receptors, which are located on both sympathetic and parasympathetic postganglionic neurons. The endogenous ligand for this receptor is acetylcholine (nicotine is not naturally found in humans). Therefore, smoking stimulates both sympathetic (increased heart rate, blood pressure) and parasympathetic (intestinal motility, relaxation) systems, releasing a whole range of hormones and neurotransmitters into the circulation.
Addiction: nicotine causes dopamine release from the nucleus accumbens, mediating reward and addiction
Carcinogen: nicotine does not initiate carcinogenesis, but it does promote initiated cells by nicotinic cholinergic receptor signalling in the lungs. Nicotine has been shown to inhibit apoptosis, proliferate cells, and cause angiogenesis in lung tumours.
Distribution of carcinogens: Cigar and pipe tobacco smoking produces relatively large particles that only reach the upper airways, unlike cigarette smoking, which produces fine particles that reaches the distal airways. Thus, cancer risk is lower with cigar and pipe smoking. The addition of anti-irritants (e.g. menthol) to cigarettes allows deeper inhalation and a more rapid rise in serum nicotine levels, increasing the addictiveness of cigarettes.
Smoking cessation: smokers at all ages can benefit from the cessation of smoking; however, the risk still remains elevated compared to never smokers.