Tobacco and Cancer|Smoking Related Cancers




Tobacco is derived include Nicotiana rustica and Nicotiana tabacum. There are 1.2 billion smokers in the world and hundreds of millions of smokeless tobacco users. By 2030, 8.3 million people globally will die from tobacco-induced disease, and tobacco will be responsible for 10% of all deaths globally. Smokers will lose on average 10 years of life and 50% of people who smoke will die of a tobacco-related disease. Adenocarcinoma has replaced squamous cell carcinoma as the most common type of lung cancer caused by smoking in the United States and elsewhere.

85% of lung cancer occurs in current or former smokers, with 10 fold increased risk of lung cancer in smokers compared to non smokers. Cancer prevention study trial II showed One pack of cigarettes smoking per day for 30 years increases risk of lung cancer by 20-60 fold in men and 14- 20 fold in women. Environmental Tobacco Smoke contributes to 20-50% of lung cancer in never smokers.

What is Mainstream and Sidestream smoke?

Tobacco combustion results in the formation of mainstream smoke and sidestream smoke.

  • Mainstream smoke : generated during puff drawing from the burning zone of a tobacco product
  • Sidestream smoke is emitted from the tobacco product into the air between puffs, produced at lower burning temperature, richer than mainstream smoke in certain carcinogens, e.g., aromatic amines.

What is Secondhand Smoke and Thirdhand Smoke?

Secondhand Smoke

It includes smoke breathed out by a smoker and smoke from the burning end of cigarettes, cigars, pipes, small amounts of smoke that escape during puff drawing and some agents that diffuse through the wrapping materials into the air.

It causes 30% to 150% increase in risk among women most heavily exposed. 37 published epidemiological studies resulted in the conclusion that there was an elevated risk of 24% among nonsmoking wives of smoking husbands, when compared with nonsmoking wives of nonsmoking husbands.

It is composed of nearly 4,000 different chemicals and over 150 toxins including carbon monoxide

Sidestream smoke comprises ~85% of total SHS, mainstream smoke constitutes <15% of the overall SHS.

Thirdhand smoke

THS is, in the words of The New York Times, “the invisible yet toxic brew of gases and particles clinging to smokers’ hair and clothing, not to mention cushions and carpeting, that lingers long after secondhand smoke [SHS] has cleared from a room.”

Genetic Susceptibility for cancer due to Smoking

Individuals with germ line mutations affecting expression of genes regulating cell cycle progression or response to DNA damage appear to have increased lung cancer risk. A threefold increase in lung cancer risk has been observed in patients with Li-Fraumeni syndrome who smoke relative to smokers without p53 germ line mutations.

Interestingly lung cancer susceptibility is influenced by genetic variation in a gene encoding for a nicotine receptor. The association of this genetic variant with lung cancer may actually be mediated through its effect on smoking behavior. Individuals with this variant generally smoked more cigarettes per day and showed more nicotine dependence than people without the variant. This finding suggests that the gene variant actually influences an individual’s exposure to an environmental agent (tobacco smoke), and it is this higher exposure that is then responsible for the individual’s increased risk of cancer.

Different effects of smoking on Men and Women

Women smokers are more likely than men to develop adenocarcinoma of the lung, and women who have never smoked are more likely to develop lung cancer than men who have never smoked. Furthermore, the 5-year survival rate for women who have lung cancer is 15.6%, while it is 12.4% for men. Women survive longer after surgical resection of early-stage lung cancer as well as after treatment of metastatic disease; female sex has been associated with longer survival in SCLC as well.

Hormonal, genetic, and metabolic differences between the sexes are believed to account for these clinical differences. Indeed, estrogens were found to be involved in lung carcinogenesis, either by acting as estrogen receptor ligands and activating cellular proliferation pathways, or by metabolic activation to reactive intermediates that can produce DNA adducts and cause oxidative damage.

Effect of Nicotine on human body

It accelerates release of neurotransmitter dopamine in the brain’s Nucleus Accumbens. This dopamine is responsible for the feeling of pleasure, emotions, and addictionNicotine stimulates the mesolimbic dopaminergic system and increases extracellular concentrations of dopamine in the nucleus accumbens.

This enhances the incentive value of the smoking behaviours, making them more likely to be repeated. This is called “reward system”. The nucleus accumbens has also been implicated in drug reinstatement or relapse.

What are the different forms of tobacco products available?

Cigarettes are the main type of tobacco product consumed in the world. Other smoked products include-

  • Kreteks, which are clove-flavored cigarettes – Indonesia
  • Sticks – Papua New Guinea
  • Bidis – tobacco wrapped in temburni leaf and tied with a string -India and neighboring areas
  • Cigars and pipes
  • Water pipe smoking/Hookah – United States,India
  • Smokeless tobacco products – chewing tobacco, moist snuff, which is placed between the cheek and gum, and pan or betel quid

Difference between cigars and cigarettes

Alkaline pH of smoke Acidic pH of smoke
Sufficient absorption of nicotine in oral mucosa Reduced absorption of nicotine in oral cavity
No inhalation of smoke into lungs Inhalation of smoke into lungs
Upper airways affected more Lower airways affected more

Difference between Filter and Non-Filter Cigarettes

Most cigarettes consumed in industrialized nations contain filters, which reduce tar within inhaled smoke, resulting in deposition of carcinogens deeper in the lungs. In addition, modern tobacco blends contain higher amounts of nitrates, which on burning, form nitrosamines such as NNK. Interestingly, smokers who convert to low-tar and nicotine (low-yield) cigarettes often compensate by smoking more cigarettes, puffing more vigorously, and inhaling deeper thereby expose more peripheral airways and cells (with a predilection to adenocarcinoma) to carcinogens.

Filter contains cellulose acetate that reduces tar in inhaled smoke. In filter cigarettes, due to forceful inhalation, there is deposition of carcinogens deeper in the lungs. The chances of cancer are almost similar, but in Cancer prevention study II trial in people 30 years or older ( current , former smokers and non smokers) it was seen that lung cancer was highest in high tar, non filter brands.

Various cancers caused by tobacco 


In decreasing order of evidence, following are the types of cancers caused by tobacco-

Lung AML Adrenal gland ALL
Oropharyngeal Cervical Gall Bladder Breast
Laryngeal Colorectal Genital Childhood cancers
Bladder Liver Sinonasal Ovary
Esophageal Prostate Thyroid Skin
Renal     Testis

Smoking and oropharyngeal cancer

Smoking is an independent risk factor in 80% to 90% of patients who present with cancer of the oral cavity. Abstaining from the use of cigarettes causes 30% reduction in the risk of cancer in those quitting from 1 to 9 years and a 50% reduction in those who quit for more than 9 years. “Reverse smoking” or Chutta is associated with increase in cancer of the hard palate.

Smoking and esophageal cancer

70 % of squamous cell carcinomas of the esophagus have been attributed to smoking tobacco for longer than 6 months . There appears to be a dose response effect related to the duration and intensity of smoking, with upto 50% reduction in risk of developing squamous cell carcinoma of the esophagus for those who quit smoking.

On the other hand, there is an inverse relationship between risk and the length of time since cessation of tobacco use. Quitting smoking does not decrease the risk of adenocarcinoma and it remains elevated for decades after smoking.

Smoking and pancreatic cancer

Tobacco smoke exposure plays a significant role in the development of pancreatic adenocarcinoma. It has been estimated that tobacco smoking contributes to the development of 20% to 30% of pancreatic cancers.

The strongest associations between cigarette smoking and pancreatic cancer have been observed when the pack years smoked were within the previous 10 years. Smoking cessation can reduce this risk, which in one study approached that of a never-smoker after 5 years of smoking cessation.

Smoking and gastric cancer

Smoking is a risk factor for adenocarcinoma of stomach, and it synergistically increases with alcohol consumption. Quitting smoking does not reduce the risk of stomach cancer.

What happens if a person with cancer continues to smoke?

Continued smoking following a cancer diagnosis decreases treatment effectiveness and increased risk of treatment-related complications.

It is a predictor of cancer recurrence, risk of second cancers, disease specific survival, and overall survival. It is often associated with poor performance status and health-related quality of life.

Patients who continue to smoke post surgical procedures have increased risk of complications. This increased risk has been observed among patients who undergo thoracotomy for suspected lung cancer, in which current smokers are twice as likely to experience a respiratory complication.

Current smoking has been linked to adverse outcomes among women who receive reconstructive surgery for breast cancer. They have increased mastectomy flap necrosis, abdominal flap necrosis, and hernia.

Tissue hypoxia resulting from smoking may be caused by both increased levels of carboxyhemoglobin levels, limiting the oxygen carrying capacity of the blood, and by compromised capillary blood flow due to nicotine-induced vasoconstriction.

Patients who continue to smoke following radiation – Head and neck cancer patients who received radiation treatment and yet continued to smoke were significantly less likely to a have a complete response to treatment, and increased mucositis, xerostomia, poor voice quality, and disfigurement.

Hypoxia caused by high carbohemoglobin levels in smokers may modulate tumor response to radiation.

People who continue to smoke following chemotherapy may experience more severe treatment-related toxicities. Smoking may reduce the effectiveness of certain anticancer or cancer preventive agents.

In lung cancer cell lines, nicotine induces resistance to chemotherapy-induced apoptosis (cisplatin, etoposide) by modulating mitochondrial signaling, decreases apoptosis via nuclear factor κB (NF-κB)–dependent survival and Akt-dependent proliferation and has been shown to inhibit apoptosis-induced cisplatin in human oral cancer cell lines.

Also, the likelihood of having EGFR abnormalities decreases as exposure to tobacco increases.

Effect on health-related quality of life – Continued smoking also appears to negatively affect health-related quality of life (HRQOL) outcomes, both short term and long term.

Several studies of head and neck cancer patients indicate that continued smoking is a significant predictor of several HRQOL domains, such as vitality, physical functioning, social functioning, emotional functioning, and general health perceptions 12 months following treatment.


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