Lung Cancer,Causes

It is estimated that tobacco smoking causes 80% of lung cancer deaths in men and 75% of lung cancer deaths in women. The more cigarettes that are smoked each day and the younger the age at which smoking began, the greater the risk of lung cancer. Lung cancer death rates are lower among individuals who use filter cigarettes and low-tar/low-nicotine brands, but such rates are significantly increased when compared with death rates in nonsmokers.



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People who quit smoking have a lower risk of developing lung cancer, and, after 10 to 15 years, their lung cancer death rates approach the rates of nonsmokers. Pipe and cigar smokers have higher lung cancer death rates than nonsmokers, but they have lower lung cancer death rates than cigarette smokers.

"Competing risk factors" such as secondhand smoke, asbestos, radon, occupational exposures, age, race, sex, and heredity also may play a role in lung cancer development. Additionally, there are some studies suggesting that lung cancer may be prevented by dietary micronutrients such as carotenoids, vitamin C, vitamin E, and selenium.

Smoking
Cigarette smoking is distinctly the greatest risk factor for lung cancer. There is a significant "dose-response" relationship between the number of pack-years smoked and lung cancer risk; that is, the more a person smokes and the longer he or she smokes, the greater the risk of lung cancer.

How exactly does cigarette smoking cause lung cancer? This question has not yet been answered definitively. But the most likely cause is the toxic mix of chemicals found in tobacco smoke. The major cigarette smoke chemicals that have been studied with respect to lung cancer are polycyclic aromatic hydrocarbons (PAHs), nicotine, nicotine by-products, tobacco-specific nitrosamines (TSNAs), metals such as nickel and cadmium, and radioactive polonium 210 (210Po).


About Tobacco . . .

Types of Tobacco In the United States, the main commercially grown species of tobacco is Nicotiana tabacum. Within this species, the types of tobacco used in cigarette products for America, western Europe, and Japan include bright (Virginia, flue-cured), Burley, Maryland, and oriental (aromatic) tobaccos. Cigarettes made in the United Kingdom and Finland primarily use bright tobaccos. Both varieties of cigarettes, when ignited, create smoke particles containing nicotine. Such "mainstream" smoke particles—minus water and nicotine—are the "tar" produced by burning cigarettes.

Tobacco Additives Cigarettes are made from sheets of reconstituted tobacco. Special solutions are used to keep the tobacco mixture intact, and chemicals known as humectants are added to maintain tobacco moisture. In addition, trade secret flavorants are included to make the product taste better during smoking. Such tobacco additives, when burned, may yield undesirable compounds. For example, the burning of licorice flavorant may produce chemicals known as polycyclic aromatic hydrocarbons (PAHs), and the burning of sugar may increase tar and nicotine in the smoke. Coumarin, a known cancer-causing substance in animals, has in the past been used as a tobacco additive. It is also likely that commercial tobaccos contain up to a few parts per million of the pesticides DDT and DDD, as well as the agricultural chemical maleic hydrazide.



About 400 to 500 separate gaseous substances are present in the smoke of a nonfilter cigarette. The major elements of cigarette vapor include nitrogen, oxygen, carbon dioxide, carbon monoxide, and water; other noteworthy substances include nitrogen oxides, hydrogen cyanide, formaldehyde, benzene, and toluene. The particles of cigarette smoke contain at least 3500 individual compounds such as nicotine, tobacco alkaloids (nornicotine, anatabine, anabasine), polycyclic aromatic hydrocarbons (PAHs; e.g., benzo(a)pyrene, B(a)P), naphthalenes, aromatic amines, phenols, and tobacco-specific nitrosamines (TSNAs).



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Tobacco-specific nitrosamines (TSNAs) are formed during tobacco curing and processing. TSNAs are chemicals that are suspected of causing lung cancer in humans. In rodent studies, regardless of the where or how it is applied, the TSNA known as NNK produces lung adenomas -benign tumors of epithelial (surface cell) tissue—and lung adenocarcinomas—malignant epithelial tumors with gland-like characteristics. The TSNA known as NNAL also produces lung adenocarcinomas in rodents, although it is a more powerful pancreatic carcinogen (cancer-causing substance) in rats.

Some of the TSNAs found in cigarette smoke particles are N-nitrosonornicotine (NNN), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosoanatabine (NAB). Other TSNAs include 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N-nitrosoanatabine (NAT), N-nitrosoanabasine (NAB), 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL), and 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butyric acid (iso-NNAC). The U.S. National Academy of Science estimates that a pack-a-day smoker is exposed to about 17 micrograms (mg) of cancer-causing TSNAs.

Cigarette smoke contains the following approximate TSNA levels:


Approximate TSNA Levels in Cigarette Smoke

NNN NAT NAB NNK Total TSMAs
Nonfilter 278 236 30 156 700
Filter 209 172 21 156 558


Manufacturers can reduce the levels of TSNA in cigarette smoke by using lighter tobacco blends and by selecting parts of the tobacco plant that are low in nitrate—a forerunner of TSNAs. Yet tobacco blends with low amounts of nitrate may have higher levels of polycyclic aromatic hydrocarbons (PAHs) in mainstream smoke.

Polycyclic aromatic hydrocarbons (PAHs) also are believed to be major contributors to lung cancer risk in smokers. PAHs are "procarcinogens" that are metabolized, or broken down by the body into reactive substances. For example, the chemical benzo(a)pyrene is changed into a compound that is known to react with human genetic material (DNA) and form DNA "adducts." It is thought that such adducts may cause problems with lung cell reproduction that eventually may lead to lung cancer. Lung cancer patients who still smoke have higher levels of PAH-DNA adducts than smokers without lung cancer.

Table 2 provides estimates of PAH levels in cigarette smoke.


PAH levels in Cigarette Smoke (ng/cigarette)
Benzo(a)pyrene 10–50
5-Methylchrysene 0.6
Dibenz(a,h)anthracene 40
Benzo(b)fluoranthene 30
Benzo(j)fluoranthene 60
Chrysene 40–60
Benzo(e)pyrene 5-40





The International Agency for Research on Cancer (IARC) has declared that some PAHs in tobacco smoke show "sufficient" evidence of cancer-causing effects (carcinogenicity) in laboratory animals. Such PAHs include benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(h)fluoranthene, chrysene, dibenz(a,h)anthracene, dibenzo(a,i)pyrene, dibenzo(a,l)pyrene, indeno(1,2,3-cd)pyrene, and 5-methylchrysene.

Other chemicals within tobacco may damage the lungs. Tobacco contains at least 30 metals, although the most toxic of these—nickel and cadmium—are present in only small quantities. Most metals found in tobacco come from the soil, fertilizers, or agricultural sprays. The element polonium 210 (210Po), which is a radioactive compound, also has been identified in the particulate portion of cigarette smoke (0.03 - 0.07 pCi per cigarette).