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Cigarette Smoking and Lung Cancer

Cigarette smoking is the single 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 for lung cancer.

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

Approximately 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).

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 (substance that causes cancer of the pancreas) 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 daily.

Cigarette smoke contains the following approximate TSNA levels:

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. However, 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 thought 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.

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 in 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).

Lung Cancer, Cigarette Smoking and Lung Cancer reprinted with permission from oncologychannel.com
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