[MOL] Lung and Larynx Risk Factors [02008] Medicine On Line

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[MOL] Lung and Larynx Risk Factors

Lung and Larynx

Jay H. Lubin, Ph.D.*

Primary lung cancer accounts for about 15 percent of all cancer cases (19 percent in males and 11 percent in females) in the United States; however, because of its high death rate, it accounts for 29 percent of all cancer deathsÑ35 percent in males and 21 percent in females (Boring et al., 1994). The overall 5-year relative survival rate is only 13 percent (Ries et al., 1994).

Lung cancer remains the leading cause of cancer death in most countries. Maoris of New Zealand experienced the highest incidence rate in the world among males, with a world standardized rate of 119.1 per 100,000 (Parkin et al., 1992). U.S. black men were near the highest, with an incidence rate of 90.0 per 100,000. Low rates were noted for Israel, India, and Latin American countries.

The worldwide incidence of lung cancer is substantially lower in females--a difference generally attributed to lighter tobacco consumption by women, although other factors may play a role. For example, high levels of indoor and outdoor air pollution have been postulated as an important contributor to the high rates of lung cancer among females in China, whose smoking prevalence is relatively low (Blot and Fraumeni, 1992).

In the United States, lung cancer incidence has risen more sharply in females (4.6 percent annual change) than in males (0.5 percent annual change) in recent years, reflecting the growing popularity of cigarette smoking among females over the past several decades (Ries et al., 1994). Currently, more women die each year from lung cancer than breast cancer (Boring et al., 1994).

Although overall age-adjusted mortality rates of lung cancer continue to rise in the United States, rates have begun to decline for those under the age of 45 (Devesa et al., 1989). The decrease is greatest among white men, but a decrease among black men and white and black women has also occurred. If trends continue, overall lung cancer mortality rates will start to decline among men in the 1990s and among women after the year 2000.

Cigarette smoking is the major cause of lung cancer. The link was first suspected in the 1920s and 1930s, and today, after multiple case-control and cohort studies, the overwhelming evidence is documented in more than 20 reports of the U.S. Surgeon General. Smoking is currently estimated to cause 85 percent of all lung cancer deaths. Lung cancer mortality increases with increasing dose, as determined by number of cigarettes smoked daily, smoking duration, and inhalation patterns. The risk of dying from lung cancer is 22 times higher among male smokers and 12 times higher among female smokers than among people who have never smoked (U.S. DHHS, 1990).

Cessation of smoking reduces the risk of death from lung cancer; after ten years the risk of lung cancer death among former smokers is about 50 percent of the risk of continuing smokers (U.S. DHHS, 1990). Those who reduce their daily usage and those who smoke filtered, low-tar cigarettes gain some benefit, although they still have lung cancer risks much higher than nonsmokers (Lubin et al., 1984).

Environmental tobacco smoke (ETS) has been determined to increase the risk of lung cancer in nonsmokers. This conclusion, presented in both the 1986 U.S. Surgeon General's Report (U.S. DHHS 1986) and a Report of a Committee of the National Academy of Sciences (NAS 1988), was based on a variety of evidence including more than 20 epidemiologic studies, as well as laboratory analyses which show the components of sidestream smoke to be qualitatively similar to mainstream smoke. Evidence suggests that persons exposed to ETS are subjected to a lung cancer risk equivalent to smoking 0.1 to 1.0 cigarettes per day.

Increased risk of lung cancer has also been associated with the smoking of pipes and cigars, but at a lower level of risk than that for cigarettes. This may be due to a less intense pattern of smoking, with cigar and pipe smokers typically inhaling less deeply and less frequently.

Radon is an inert gas produced by the radioactive decay of radium and uranium. While concentrations of these elements vary widely, they are found everywhere in the crustal rock of the earth. Radon itself is radioactive and may cause lung cancer. Studies of underground miners exposed to radon have consistently shown an increased risk of lung cancer with greater cumulative exposure to radon and its short-lived decay products (Lubin et al., 1994; NAS, 1988; Samet 1989). The results of these studies, together with animal studies, suggest that radon exposure is a cause of lung cancer, at least at levels historically found in mines.

Radon may also enter homes by migrating from the earth through cracks in the foundation, or through the hole for a sump pump, or, in rare cases, via private water wells, by dissolving in drinking water. Although the radon concentration in some homes may reach levels found in mines, average domestic cumulative lifetime exposure to radon is about 5 to 15 times lower than for miners. Based on miner studies, it has been estimated that radon may cause 6,000-24,000 lung cancer deaths each year in the United States (Lubin and Boice, 1989). However, because of uncertainties in using miner-based results, the precise public health consequences of domestic exposure to radon is currently an important unresolved issue. Results of ecologic studies and case-control studies, using either indirect estimates of personal exposure or direct measurements of indoor radon concentrations, have been mixed in showing an association between radon level in the home and lung cancer risk (Samet 1989).

Studies of occupational groups have identified several other respiratory carcinogens, although it is difficult to assess their overall public health impact. Some of these exposures--such as radon--may be widespread in the population but at very low levels, while other exposures may have their greatest impact on subgroups of the population, as with asbestos exposure among shipyard workers. It should be noted that the carcinogenic effect of some of these exposures, e.g., asbestos, is enhanced by tobacco smoke.

Exposure to airborne asbestos appears to be the largest cancer threat in the workplace, raising the risk of lung cancer and mesothelioma (a cancer that arises in the lining of the chest cavity, or mesothelium) as well as asbestosis, a lung disease (Blot and Fraumeni, 1992). The risk of developing these three diseases is substantially higher for workers in a number of asbestos industries, including miners and millers, and textile, insulation, shipyard, and cement workers. Lung cancer is the major asbestos-related disease, and accounts for death in about 20 percent of some men exposed to asbestos for long periods of their work life (Selikoff et al., 1979). Even men who worked for short periods in shipyards during World War II have a higher risk of developing lung cancer than workers never exposed to asbestos (Blot et al., 1978; 1980).

Lung cancer is also one of the major effects of high doses of ionizing radiation. Excesses of lung cancer have been reported among some patients who received radiation therapy, and among atomic bomb survivors in Japan (Beebe et al., 1978), where both gamma rays and neutrons were released.

A number of other occupational agents contribute to the incidence of lung cancer: mustard gas, chloromethyl ethers, chromium, nickel, and inorganic arsenic.

Air pollution has been suspected as a cause of lung cancer, but it has been difficult to establish definite links. Of special concern are the effects of the byproducts of the combustion of fossil fuels, most notably polycyclic aromatic hydrocarbons (PAHs). Studies have suggested that exposure to benzo(a)pyrene may increase lung cancer risk. In both urban and rural areas of China, exceptionally high levels of indoor air pollutants from the use of coal for heating and for cooking, along with cigarette use, have been implicated in the high rate of lung cancer (Mumford et al., 1987; Xu et al., 1989). Although suggestive, the association of lung cancer and PAHs has not yet been conclusively demonstrated, as other components of air pollution may also be carcinogenic.

Finally, there is laboratory evidence of a protective effect against lung cancer with increased intake of vitamins A (retinol and precursor carotenes), C, E, selenium, and other micronutrients. Epidemiologic studies have provided support for some of these associations. The clearest and most consistent associations occur with the consumption of fresh fruits and vegetables. Studies show that risk of lung cancer was reduced by as much as 50 percent among those with the greatest compared to those with the least consumption of these foods (Blot and Fraumeni, 1992). The precise component responsible is still uncertain, but most attention has been focused on carotenoids, particularly beta-carotene.

Approximately 12,500 new cases of cancer of the larynx, or voicebox, occur each year, 9,800 in males and 2,700 in females (Boring et al., 1994). It has an incidence pattern similar to that of cancers of the mouth and throat, occurring more often among men than women and more often among blacks than among whites. The annual incidence of laryngeal cancer among U.S. white men is 7.8 cases per 100,000 population, and 1.7 among white women. Among black men, the annual incidence is 13.0 per 100,000, and 2.7 among black women (Ries et al., 1994).

In the United States between 1973 and 1991, the incidence of laryngeal cancer declined 0.6 percent annually in white males, but increased 1.6 percent in white females over the same time. In blacks, the annual incidence increased in both sexes, 0.9 percent in males and 2.3 percent in females (Ries et al., 1994).

Risk factors for laryngeal cancer include tobacco, alcohol, asbestos, and nickel and mustard gas exposure. As with cancers of the lung, mouth, and throat, many cases of laryngeal cancer can be attributed to cigarette smoking. Cigarette smokers have almost a ten-fold greater risk for laryngeal cancer than do nonsmokers, and risk increases with increased cigarette smoking (Wynder et al., 1982). Not only is heavy alcohol consumption a risk factor, but tobacco and alcohol together appear to act synergistically.

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