Fact Sheets: The Facts about Smoking

Source: National Cancer Institute (NCI) (November 2007) Cigarette Smoking and Cancer: Questions and Answers

Key Points

• Cigarette smoking causes 87 percent of lung cancer deaths and is responsible for most cancers of the larynx, oral cavity and pharynx, esophagus, and bladder.
• Secondhand smoke is responsible for an estimated 3,000 lung cancer deaths among U.S. nonsmokers each year.
• Tobacco smoke contains thousands of chemical agents, including over 60 substances that are known to cause cancer.
• The risk of developing smoking-related cancers, as well as noncancerous diseases, increases with total lifetime exposure to cigarette smoke.
• Smoking cessation has major and immediate health benefits, including decreasing the risk of lung and other cancers, heart attack, stroke, and chronic lung disease.

Tobacco use, particularly cigarette smoking, is the single most preventable cause of death in the United States. Cigarette smoking alone is directly responsible for approximately 30 percent of all cancer deaths annually in the United States. Cigarette smoking also causes chronic lung disease (emphysema and chronic bronchitis), cardiovascular disease, stroke, and cataracts. Smoking during pregnancy can cause stillbirth, low birthweight, Sudden Infant Death Syndrome (SIDS), and other serious pregnancy complications. Quitting smoking greatly reduces a person’s risk of developing the diseases mentioned, and can limit adverse health effects on the developing child. 

Tobacco Smoking and Cancer

Since the early 1950s a large number of studies have shown correlations between smoking history and cancer of the lung as well as other organs. Evidence linking smoking with lung and other cancers has been obtained from many epidemiological studies. Many carcinogens have been found in tobacco smoke, and cigarette smoke condensate produces cancer in animals. Cancer in general and smoking induced cancer in particular usually occurs from 15 to 30 years after exposure to the carcinogen begins. Since the end of World War II, the number of deaths caused by tobacco smoking have increased sharply, because of heavy smoking during the 1930s, 40s and 50s. Tobacco smoking is estimated to be responsible for at least 30% of all cancer deaths in the U.S. and Europe. Cancer caused by tobacco smoking could reach epidemic proportions in developing countries in the near future. Since smoking causes death from heart disease, other lung diseases and other diseases, tobacco smoking can be estimated to cause approximately 5 million deaths a year worldwide, a figure which is expected to increase to 10 million deaths a year by 2030. Tobacco smoking caused 100 million deaths in the 20th century, (about twice the total number of civilian and military casualties from World War II), but could reach 1 billion deaths in the next century, unless something is done to decrease the number of people exposed to cigarette smoke. About one half of all lifetime tobacco smokers will die because of their habit.

The evidence shows that tobacco smoke is a carcinogenic mixture that can cause cancer in many different organs in human beings. Smoking is also highly synergistic with other environmental carcinogens. For example, the incidence of lung cancer among uranium miners who also smoked was extremely high. The same pattern has been seen for asbestos workers and many other groups of people exposed occupationally to chemical carcinogens. One of the most informative studies relates to the incidence of lung cancer as a function of gender. Historically this has been a predominantly male disease. However, after World War II women began to smoke with equal frequency to men. The frequency of lung cancer in women began a steep upward trend just 20 years later, paralleling the curve of smoking incidence. Lung cancer deaths now outrank breast cancer deaths as the leading cause of cancer mortality in women.

In 1986, the International Agency for Research in Cancer, an international organization that determines the carcinogenic potential of chemicals and materials, found that tobacco smoking was carcinogenic in humans (cigarette smoking was given a 1A classification, reserved only for those chemicals and processes that have been proven to be human carcinogens), and concluded that tobacco smoking caused cancers of the lung, renal pelvis, bladder, oral cavity, pharynx, larynx, esophagus, and pancreas. This judgment, reached by an international panel of medical and scientific experts was based on published data and incorporated consideration of bias or confounding factors, the presence of dose–response relationships, biologic mechanisms, and the consistency of findings from different independent investigations using different study designs, from different countries.

Since 1986, further evidence shows that smoking tobacco also causes cancer of the nasal cavity, paranasal sinuses, and nasopharynx; stomach; liver; kidney; cervix uteri; and adenocarcinoma of the esophagus and myeloid leukemia. Cancer can be caused by smoking cigarettes, pipes, and cigars. Cigar and pipe smoking causes cancers of the oral cavity, oropharynx, hypopharynx, larynx, esophagus, and lung. The idea that the risk of cancer from pipes and cigars is much less than that of cigarettes is not correct. Dose–response relationships have been found with the amount of cigar and pipe tobacco smoked.

Cigarette smoke contains an amazing variety and number of carcinogens; in fact, it would be hard to deliberately formulate a more carcinogenic mixture than cigarette smoke. In the gas phase are found several nitrosamines such as dimethylnitrosamine, urethane, formaldehyde, and vinyl chloride, all complete carcinogens. In the particulate phase are found the carcinogens benzopyrene, beta-naphthylamine, methylchrysene, benzofluoranthene, benzanthracene, and more than two dozen other aromatic hydrocarbons. Tumor promoters and cocarcinogens such as pyrene, naphthalene, catechol, phenols, methylindoles, methylcarbazoles, and others are also found in smoke. Besides these hydrocarbons, cigarette smoke contains carcinogenic metals such as nickel and cadmium and the radioactive element polonium 210. A large number of the constituents of smoke have proven positive in carcinogenic bioassays. An important class of chemical carcinogens, the nitrosamines, are produced in cigarette smoke from nicotine, the addictive agent.

Because tobacco smoke contains so many potent carcinogens of so many types, it is difficult to attribute the carcinogenicity of tobacco to any particular compound. The most likely situation is that various different combinations of carcinogenic compounds with different mechanisms of action act to produce malignant cancer. The active narcotic agent in tobacco, nicotine is chemically converted during curing, processing, and burning into a series of carcinogenic compounds called nitrosamines. These agents are tobacco specific; they are found in snuff and chewing tobacco as well as in cigarette mainstream and sidestream smoke. The nitrosamines NNN and NNK produce tumors in lung, nasal cavity, esophagus, and trachea, in rats, mice and hamsters. These agents require metabolic activation for their carcinogenic action; human trachea, lung, and other respiratory tissues have been shown to metabolically activate NNN and NNK, and they have been detected in the urine of smokers.

The presence of radioactive elements in cigarette smoke has been known since the 1960s. These elements include radium 226, radon-228, thorium-228, traces of other elements and polonium-210. Polonium-210 is the most abundant of these in smoke. It is an alpha emitter and is volatile at the temperature of a burning cigarette. Alpha radiation is an intense form of radioactivity known to be carcinogenic in animals and humans. Due to very low solubility, polonium-210 is retained and concentrated in lung tissue longer than other tobacco smoke constituents.

Mechanisms of Tobacco Carcinogenesis

Scientists have used biochemistry and molecular biology to investigate the mechanisms of tobacco carcinogenesis. Metabolites of chemical compounds present in tobacco, DNA adducts (a chemical form of attachment of a carcinogen to DNA), genetic mutations in the DNA, and alterations of chromosomes have all been identified in human beings in connection with tobacco smoking.

Carcinogenic compounds present in tobacco smoke, produce functional destructive mutations in a critical gene - p53, which is one of the most important cancer related genes. A specific pattern of mutations in the p53 gene has been identified as a molecular signature of lung cancer caused by tobacco smoking. DNA adducts of these same compounds are present in human tissues exposed to tobacco smoke. Tobacco smoke also contains arylamines, such as the potent carcinogen 4-aminobiphenyl, which causes bladder cancer. 4-Aminobiphenyl forms DNA-adducts in bladder cells in the urine and in bladder biopsies from smokers.

One of the most well known chemical carcinogens in tobacco smoke is benzo[a]pyrene and DNA adducts of this chemical have been found in the cervical tissues of smokers. Another famous carcinogen in tobacco smoke is benzene, a chemical known to cause leukemia. Smokers have increased cytogenetic damage of the type associated with effects of benzene.

The only good news about smoking is that individuals who stop smoking reduce their cancer risks dramatically. The earlier an individual stops smoking, the lower the risk of lung cancer, and all other causes of death by smoking. For example, the probability of getting lung cancer by age 75 for a man who starts smoking at age 18 drops from 16% to 6% if he stops smoking by age 50, and it drops all the way to 2% is he stops by age 30. It is therefore critical for public health to assist people in their efforts to stop smoking.

Non-smokers who breathe smoke (called sidestream smoke) from other people's cigarettes (i.e., involuntary smoking) are exposed to the same carcinogens as smokers, although at much lower doses. Children of smokers have seven times the incidence of asthma and upper respiratory infections as children of nonsmokers.

For the past decade environmental tobacco smoke (ETS) or passive smoking, has been investigated as a cause of lung cancer. Recent definitive studies and reviews of many studies have used the nonsmoking spouses of smokers as the test group. Spousal exposure is well defined and has been validated using biochemical markers. Non-smokers who live with smokers are also more likely to mix socially with smokers. Other studies have used workplace exposure to ETS, which are more variable and therefore harder to study scientifically. The results from domestic exposure to ETS can be used to judge the risk from workplace exposure, depending on the exposure levels, which in some cases, such as in bars and restaurants can be extremely high.

In a recent meta-analysis and general review of all published studies on ETS and cancer, it was found that seven published studies showed a significant excess risk of lung cancer in the non smoking spouses of smokers. Other studies showed increased risks, but because the number of cases were small, they were not statistically significant. This problem can be overcome by meta-analysis, which combines all the studies into one large study. When this was done, the total combined relative risk of lung cancer from 37 different studies on women was 1.24 or 24%. This increased cancer risk was statistically significant, meaning that it was not due to chance or error. The risk of lung cancer from exposure to environmental tobacco smoke was the same for men and women, and did not depend on geographical location, or many other parameters.

A significant dose-response relation was seen between the number of cigarettes smoked by the husband and the risk of lung cancer in their non smoking wives. The risk increased by 23% for every 10 cigarettes smoked per day by the husband (88% if he smoked 30), and by 11% for every 10 years of exposure (35% for 30 years' exposure). The risk of lung cancer from ETS was higher for squamous and small cell carcinoma (58%) than for adenocarcinoma (25%). Since smoking is more strongly related to squamous and small cell carcinoma than adenocarcinoma, this suggests that exposure to environmental tobacco smoke is equivalent to smoking at a low dose.

The high risk of lung cancer in non-smokers who live with smokers has been claimed to be an illusion caused by statistical or analytical errors called bias or confounding. Because of the growing social stigma attached to cigarette smoking, some smokers may say that they are non-smokers. This could lead to a bias called misclassification. These people would be more likely to develop lung cancer, and therefore lead to an over-estimate of the true risk of lung cancer in the test group of nonsmoking spouses of smokers. Other biases could come from dietary factors, and exposure to ETS in the control group. The degree of these biases have been estimated and taken into account in studies of ETS risk.

Adjustment of the observed relative risk of 1.24 for misclassification bias, dietary confounding and exposure to ETS in the control group gave a corrected final result of 1.26 or 26%. This is similar to the value obtained from extrapolation of the risk due to exposure to ETS using biochemical evidence. The chemicals nicotine and cotinine are formed from tobacco and excreted in the urine. In non smokers exposed to ETS, nicotine and cotinine concentrations are about 1.0% of those found in the urine of smokers. This suggests that non-smokers exposed to ETS have about 100 times less exposure to tobacco smoke than regular smokers. Assuming dose linearity, this would mean a 100-fold lower lung cancer risk for people exposed to ETS. Since smokers have a relative risk for lung cancer of about 20 (2000%), then ETS exposed non smokers should have a risk of about 20%, a value that is in close agreement with the observed value of 26%. This estimated excess risk of 26% corresponds to several thousand deaths per year in the U.S.

A larger and even more recent study than the one described above gave very similar results with a risk for ETS exposure of 25%. This study pooled data from 46 published papers including 6,257 lung cancer cases. In this study the non smoking husbands of women who smoked had an even higher risk (35%) than did non smoking wives of smokers. Similar conclusions were reached by studies that have examined the risk of lung cancer among non-smokers exposed to ETS in the workplace.

Public health measures to decrease exposure to ETS and to decrease smoking can save millions of lives. Medical history is full of other examples of non-medical interventions used to prevent disease and extend human life and well-being. Some examples include sewage treatment, sanitary conditions in health care, and removal of lead from paint and gasoline. Laws restricting smoking are in the same category as these examples. In cities around the world where antismoking laws have been enacted, hospital admissions for severe respiratory distress dropped dramatically. An interesting natural experiment was done in Helena, Montana. An antismoking law was enacted for Helena’s pubs and restaurants, and then 6 months later rescinded due to commercial pressure. For the six months of the ban, hospital admissions for a variety of illnesses including heart attacks dropped dramatically. When the ban was rescinded this measurable improvement in the health of the population was immediately reversed, and the rate of admissions went back to what it had been before the ban.

The effects of secondhand tobacco smoke cost the U.S. economy nearly $10 billion a year, ranging from medical bills to lost hours on the job according to an article in the Wall Street Journal. The article also states that this could encourage insurers to consider separate pricing for nonsmokers exposed to tobacco smoke.

The major health benefits of such laws can be tallied with respect to their effects on general cancer risk in the population. Such laws reduce exposure to ETS for both customers and employees. In addition, they encourage smokers to quit smoking and discourage people trying to quit from giving up. They also help to discourage young people from starting to smoke, one of the most important and difficult tasks in the anti-smoking campaign.

The general trend toward decreased smoking incidence in the U.S. and Western Europe, and the trend toward greater restrictions on smoking in public places have gone together in recent years. Anti-smoking laws are an important part of the general public health agenda, which seeks to improve and prolong each precious human life in our community.

• For additional information about cancer or tobacco use, call 1–800–4–CANCER or visit the NCI’s Web site about tobacco at www.cancer.gov/cancerinfo/tobacco.
• For help with quitting smoking, call NCI’s smoking cessation quitline at 1–877–44U–QUIT or visit NCI’s smoking cessation Web site at www.smokefree.gov.
• Information about the health risks of smoking is also available from Centers for Disease Control and Prevention’s Office on Smoking and Health (OSH) at 1–800–CDC–1311 (1–800–232–1311) or via their Web site at www.cdc.gov/tobacco.

To inquire about Center for Environmental Oncology activities, please send an e-mail to envonc@upmc.edu or call 412-623-3375.