Cigarette smoking has been identified as the second leading risk factor for death from any cause worldwide. In 2000, an estimated 4.83 million deaths were attributed to cigarette smoking globally, with nearly half occurring in the developing world. With a population of 1.3 billion, China is the world's largest producer and consumer of tobacco and bears a large proportion of deaths attributable to smoking worldwide (Gu et al 2009, NEJM, 360, pp150).

Lung cancer is the leading cause of death among smokers. In 2007, there were an estimated 213 380 new lung and bronchus cancer cases and 160 390 people died of this disease in the USA (Cancer Facts & Figures 2007). Epidemiological studies have demonstrated that most cases of lung cancer are directly attributable to cigarette smoking. Only 5-10% of all of the lung cancers occur in patients without a prior history of cigarette smoking . Compared to non-smokers, smokers have a 10 fold greater risk of dying from lung cancer and in heavy smokers this risk increases by 15-25 folds. Although associations between cigarette smoking and lung cancer are well documented, surprisingly little is known about the mechanistic basis of smoking-related lung cancer at the cellular level. This is due, in part, to the fact that cigarette smoke is a complex and dynamic mixture of more than 4,000 individual chemical constituents. Cigarette smoke has been shown to have multiple effects on gene expression primarily, the expression of xenobiotic-metabolizing, redox-regulating genes, tumor suppressor genes, oncogenes, and genes involved in the regulation of inflammation.

Nicotine is the chemical in cigarettes that makes people addictive. Higher levels of nicotine in a cigarette can make it harder to quit smoking. A report by the Massachusetts Department of Health found that the amount of nicotine in cigarettes has steadily increased over the last 6 years. Higher nicotine levels were found in all cigarette categories, including "light" brands. In addition to nicotine, cigarette contains over 19 known cancer-causing chemicals (most are collectively known as "tar") and more than 4,000 other chemicals.

Cigarette smoking, DNA adducts formation and mutation status in lung cancer:

Figure 1.

Figure 2 adapted from: American Cancer Society, 2007


Ciagerette and its toxic chemicals:

Figure 3 adapted from http://counties.cce.cornell.edu/wyoming/family/reality_check/cigarette.jpg

Some of the chemicals associated with cigarette smoke include ammonia, carbon dioxide, carbon monoxide, propane, methane, acetone, hydrogen cyanide and various carcinogens. Other chemicals that are associated with chewing or sniffing tobacco include aniline, naphthalene, phenol, pyrene, tar, and 2-naphthylamine.

Figure 4. Countries, States, and Provinces That Have Banned Smoking in Indoor Workplaces and Other Indoor Public Places. Legislation in some countries and regions (shown in green) allows for the possibility of a designated, enclosed, ventilated smoking room. Full bans are also in force in Rhode Island, Hawaii, Puerto Rico, Washington, DC, Bermuda, the British Virgin Islands, Bhutan, and the Australian Capital Territory; legislation allowing for designated smoking rooms is in force in Malta. Full bans will go into effect in Quebec in 2008 and in Montana, Utah, and Hong Kong in 2009; a law allowing for the possibility of designated smoking rooms will go into effect in Finland in 2009.

(Figure 4 adapted from Koh et al. 2007. The New England Journal of Medicine, 356 (15): 1496)

Smoking and epithelial to mesenchymal transition (EMT) pathway: which is the target pathway?

Figure 5. Epithelial to Mesenchymal Transition (EMT) and Smoke. Four main signaling pathways activated by smoke exposure may contribute to EMT. Shh is a ligand that binds to its receptor, Ptch. Binding of Hh inactivates Ptch and derepresses the transmembrane protein, Smo, resulting in positive Hh signaling. This includes DNA binding of the transcription factor Gli, and activation of its target genes, such as cyclin D and Myc. Wnt is another ligand that, when bound to its receptor, Frizzled (Fz), leads to inactivation of GSK3. This prevents proteosomal degradation of β-catenin, and leads to the translocation of β-catenin into the nucleus, where it increases protumor gene expression through complex formation with the transcription factor TCF/LEF1. In lieu of a soluble Wnt ligand, Wnt/β-catenin gene expression can be triggered by the release of β-catenin from disassembled junctions. Smoke-inducing interactions between β-catenin and the membrane glycoprotein, MUC1, appear to promote junction disassembly by out competing β-catenin for E-cadherin. ROS are produced through the activation of NADPH oxidase, and lead to the activation of the transcription factor NK-κB. The activation of NK-κB leads to decreased expression of E-cadherin through the activation of Snail and upregulated expression of Bcl2, an inhibitor of apoptosis. Smoke-induced ROS also activates the A disintegrin and metalloprotease (ADAM), TNF-α–converting enzyme, to cause cleavage of amphiregulin, a ligand for EGFR. Activation of EGFR leads to Ras/Raf/MAPK, PI3K/Akt, and Src signaling. TGF-β isoforms signal through Smads, RhoA, PI3K, and MAPK. TGF-β leads to activation of PAR6, with the subsequent loss of tight junctions through the degradation of RhoA. TGF-β–initiated activation of RhoA leads to cytoskeletal changes and increased migration.

(Figure 5 adapted from: Dasari et al., American Journal of Respiratory Cell and Molecular Biology. Vol. 35, pp. 3-9, 2006)

Smoking and Lung Cancer: Videos

http://www.youtube.com/watch?v=3Re7CwwCAw0

GREAT REASONS TO QUIT SMOKING

If you are looking for a reason to quit smoking, consider these points:

• People who quit smoking, regardless of their age, live longer than people the same age who continue to smoke.
  
• Smokers who quit before the age of 50 are twice as likely to survive the next 15 years as those who continue to smoke. Smokers who quit before the age of 35 avoid 90% of the health risk linked to smoking.
  
• By quitting smoking, you reduce your risk for developing cancer of the lung, mouth, nasal cavities, pharynx (throat), larynx, esophagus, stomach, pancreas, liver, kidney, bladder, cervix, and some types of leukemia.
  
• You also reduce your risk for developing heart disease, stroke, emphysema, chronic bronchitis, and stomach ulcers.
  
• Smoking is expensive. A one-pack-a-day habit usually costs $2,000 to $3,000 per year.
  
• Parents can set a good example for their kids by quitting. Parents and pregnant women who quit can protect their children and fetus from secondhand smoke.

American Cancer Society: http://www.cancer.org/

American Lung Association: http://www.lungusa.org/

National Cancer Institute Cancer Information Service: http://www.cancer.gov/

Figure 1. Diagrammatic summary of Oral Cancer (Oral Squamous Cell Carcinoma: OSCC) risk factors.

 Figure 2. Countries with high incidence and mortality from oral cancer.

Figure 3. A comparison of incidence of oral cancer among European populations.

Table 1. Carcinogens in cigarette smoke.

Sustained and intensive educational programs on tobacco use resulting in cessation have shown a substantial fall in the incidence of oral leukoplakia in intervention cohorts in India. Outreach programmes from hospitals can educate communities about dangers of tobacco use when combined with oral examinations for the detection of oral precancer. So far in the industrialised countries there have been no specific interventional programs reported. Dentists are uniquely placed to impact smoking rates but need further training and oral physicians and surgeons who manage red and white patches of the oral mucosa frequently fail to address this issue in a systematic way. The oncologist’s role in smoking prevention to prevent second primary tumours is gaining attention.

References and Figures adapted from Scully and Bagan (2009), Oral Oncology, 45(4-5), 301-308; Warnakulasuriya, Oral Oncology (2009), 45 (4-5), 309-316; World Health Organization. Addressing the Worldwide Tobacco Epidemic through Effective Evidence-Based Treatment. Expert Meeting March 1999, Rochester, Minnesota, USA. Tobacco Free Initiative, WHO 2000; Yang et al., Smoking in China. Findings of the 1996 National Prevalence Survey, JAMA 282 (1999), 1247–1253; Warnakulasuriya et al, Oral Oncology (2005), 41 (3), 244-260.