Epidemiology of lung cancer: A worldwide epidemic

Epidemiology of lung cancer: A worldwide epidemic

Epidemiology of Lung Cancer: A Worldwide Epidemic Barbara G. Valanis Objectives: To examine patterns and trends in lung cancer and the risk factors a...

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Epidemiology of Lung Cancer: A Worldwide Epidemic Barbara G. Valanis

Objectives: To examine patterns and trends in lung cancer and the risk factors associated with development of this disease. Data sources: Epidemiologic studies, research studies, review articles, and government reports pertaining to epidemiology of lung cancer. Conclusion: Epidemiological evidence documents that most lung cancer cases could be prevented. With 3 million persons worldwide dying annually from lung cancer attributable to smoking, cigarette smoking re-

mains the number one target for public health action to reduce cancer risk in the general population. Implications for nursing practice: A useful resource for nurses is the descriptive epidemiology of lung cancer, a knowledge base that identifies who is at risk. Linking this risk information with knowledge of strategies for reducing these risks provides a basis for planning and implementing interventions to prevent lung cancer. Copyright @1996 by W.B. Saunders Company

UNG C A N C E R is now believed to be the leading cause of cancer mortality in the world. Incidence rates continue to rise in many developed countries, l Because survival after a diagnosis of lung cancer is generally poor and early detection is generally not achievable, interventions must be aimed at prevention. Epidemiological evidence documents that most lung cancer cases could be prevented. In populations where longterm history of smoking is widespread, 83% to 94% of lung cancer incidence in males and 57% to 80% in females is attributable to a single c a u s e - cigarette smoking--and much of the rest to a few known exposures. 2 Nursing personnel are increasingly involved in planning and implementing strategies for preventing lung cancer. A useful resource for nurses doing such work is the descriptive epidemiology of lung cancer, a knowledge base that identifies who is at risk. Linking this risk information with knowledge of successful strategies for reducing these risks in population subgroups provides a basis for planning explicit interventions.

were only 11% in US blacks and 14% in US whites for the period 1986 to 1991. 3 Five-year survival is considerably higher for lung cancer diagnosed in a localized stage, 42% and 48%, respectively, for US blacks and US whites, but only 15% of lung cancer cases were diagnosed that early. Fully 44% of cases were diagnosed with distant metastases. For these cases, 5-year survival is 2%. Thus, incidence and mortality data present essentially the same conclusions. Because mortality data are more readily available, most of the data presented are based on mortality statistics. These statistics generally combine data for trachea, bronchus, and lung under the single category of lung cancer, because these three are often indistinguishable at diagnosis as to primary site.

L

PATTERNS AND TRENDS IN LUNG CANCER

Descriptive patterns of disease occurrence compared for various population groups, geographic locations, and times help to identify risk factors associated with development of a disease. Epidemiologists generally examine both morbidity and mortality data, to determine which factors are associated with disease occurrence versus survival. For lung cancer, however, morbidity and mortality patterns are similar, because for most forms of lung cancer, duration of survival after diagnosis is short. Overall 5-year survival rates (all stages combined)

International Trends" Lung cancer is now the leading cause of cancer mortality in males in all European countries and is increasingly a cause of death in the developing countries. 4 In general, rates are higher in the more industrialized countries and lower in the developing countries. Table 1 shows lung cancer incidence rates for the 10 geographic locales with the highest and lowest rates among 48 nations for which data were

From Kaiser Perroxmente Center fi~r Health Research, Portland, OR. Barbara G. Yalanis, DrPh, RN, FAAN: Senior Investigator and Director of Nursing Research, Kaiser Permanente Center for Health Research, Portland, OR. Address reprint requests to Barbara G. Valanis, DrPh, RN, FAAN, 3800 N Kaiser Center Dr, Portland, OR 97227. Copyright @ 1996 by W.B. Saunders Company 0749-2081/96/1204-000255.00/0

Seminars in Oncology Nursing, Vol 12, No 4 (November), 1996: pp 251-259

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Table 1. International Age-Adjusted Lung Cancer Death Rates per 100,000 Population for Countries with the 10 Highest and Lowest Lung Cancer Rates by Gender Men

Women

Highest rates 1 Hungary 81.6 2 Czech Republic 75.3 3 Russian Federation 72.8 4 Poland 71.3 5 6 7 8 9 10 Lowest rates 39 40 41 42 43 44 45 46 47 48

Denmark Kazakhistan Netherlands Latvia Lithuania Ukraine$

70.0 68.4 66.9 64.5 63.1 63.1

Portugal Albania§ Israel$ Sweden Uzbekistant Mauritius Mexico Tajikistan* Costa Ricat

27.9 27.4 25.7 23.7 19.7 17.2 15.9 15.0 14.3

Trinidad, Tobago*

United States Denmark Canada United Kingdom NewZealand Ireland Hungary Singapore China* Cuba*

Albania Costa Ricat Belarus Uzbekistan Portugal Tajikistan* Uruguay* Mauritius Trinidad, Tobagot 13.6 Spain

25.6 24.8 21.8 21.0 18.0 17.6 16.6 16,0 15.9 13,8 5.0 5,0 5.0 4.8 4.6 4.4 4.2 4.0 4.0 3.6

"1990 only. 71990 to 1991. $1990 to 1992. §1992. Data From Parker et al.3

available. 3 Rates for men in the 10 countries with the highest rates range from 63.1 per 100,000 to 81.6 per 100,000. Many of these high rates are in former republics of the Soviet Union, now independent nations. Denmark and Poland are other countries among the top 10 for men. Among women, a very different picture is seen; the United States, Canada, the United Kingdom, and Ireland are among the top 10. China has the ninth highest female rate. These rates range from 13.8 per 100,000 to 25.6 per 100,000. For both men and women, the lowest rates are primarily, but not exclusively among the developing nations. Spain, Portugal, and Israel, more recently developed countries, still have low rates (less than 30 per 100,000 for men and 5 per 100,000 for women). Lung cancer is increasing in these and other southern European countries and in most developing countries. In contrast, rates are beginning to decline in many developed countries, reflecting decreases in total exposure to cigarettes. 4,5 This leveling of age-adjusted lung cancer

mortality rates has been observed for men in England, Wales, Finland, Canada, Japan, Germany, Denmark, Italy, and Australia. Among women in these countries, however, rates did not begin to rise until the late 1960s or early 1970s, about 20 years later than for men, and are continuing to rise. 3 If subpopulations within countries are examined, some high-risk groups are seen. Among subpopulations, the highest incidence rates (119.1/100,000) are currently observed among men in the Maori population of New Zealand and among several black male populations of the United States, including New Orleans (115.9), San Francisco (107.4), Detroit (107.2), and Alameda county (106.9). Incidence rates are also high in Western Scotland (97.2). Among subpopulations of women, high incidence rates are also found among the Maori population and among both black and white subgroups in the U.S)

United States Patterns by Age, Race, and Gender Overall cancer incidence and mortality rates in the United States have been increasing. If lung cancer were excluded from these statistics, overall cancer rates would be decreasing. 6 Among men, lung cancer incidence and mortality began increasing in the 1930s, among women some 15 to 20 years later (Fig 1). In 1950, approximately 14,000 men and 3,000 women died from lung cancer. By 1987, these figures were 87,200 and 42,700, respectively; 115,000 of these occurred among whites and 14,000 among blacks. Between 1950 and 1986, deaths from lung cancer totaled more than 2 million. 6 In 1992, the most recent year for which statistics are complete, there were 145,943 deaths from lung cancer in the United States. The 91,405 lung cancer deaths among men represented 33% of all male cancer deaths and the 54,538 lung cancer deaths for women represented 22% of all female cancer deaths. Lung cancer is now the leading cancer cause of death for both men and women. As in many other developed countries, overall US age-adjusted lung cancer incidence and mortality rates recently began to plateau among white men, but not black men; among women, rates continue to increase regardless of race. 6,7 The decline in incidence and mortality among men was particularly notable among men less than 55 years of age beginning in the years 1985 to 1986 compared with previous years. Both incidence and

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rates tended to be in the urban areas of the southern US. Geographic variation among females is minor. In all regions, lung cancer is more common in urban counties than in rural counties.

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Autopsy and pathology studies have examined lung cancer cell type and found that squamous cell carcinoma is the predominant histologic form among men, regardless of age (53.5%). Adenoarcinoma is the most common form in women until age 60 (30.6%), after which squamous and small cell types predominate. Regardless of histologic type, more than 80% of men and women who developed lung cancer were smokers. 12 However, a recent comparison of differences in age-adjusted incidence rates for various histologic types of lung cancer by sex, race, age, and calendar time suggested that different histologic types may have different etiologies. 13Among white men in the US between 1969 and 1988, rates of adenocarcinoma and oat cell tumors increased, whereas rates of squamous cell decreased. All types increased among white women.13 RISK FACTORS

mortality rates were higher among whites than nonwhites until about 1960, when mortality rates for both nonwhite males and females began to exceed that for white males, s For both white and black males, age-adjusted lung cancer incidence rates are significantly associated with both income and education, the highest rates being among those with the lowest socioeconomic status and least education. Among white females, a U-shaped pattern was seen, with the higher lung cancer rates being found for women in the lower and upper income and education groups. Among nonwhite women, the relationships resembled those for men. Rates of lung cancer within the United States vary by geographic locale. After adjustment for demographic characteristics of residents, lung cancer mortality among white males was elevated in counties with paper, chemical, and petroleum manufacturing industries or shipbuilding, 9-u primarily along the Atlantic coast and the Gulf of Mexico, particularly Louisiana. These industries have exposures to carcinogens, including polycyclic aromatic hydrocarbons, asbestos (shipyards), low-level ionizing radiation (nuclear shipyards), and wood preservatives. Among nonwhite males, the highest

Data on patterns of disease occurrence and mortality provide us with a picture of how risk varies in absolute terms for broad demographic or geographic categories. To determine whether the factors associated with higher rates in descriptive data might have a role in causing lung cancer, analytic epidemiologic studies provide clues to specific social, behavioral, environmental, or biologic factors that may be associated with increased risk. Analytic study designs may include correlational cross-sectional studies, case-control studies, and cohort studies. A body of literature made up of many such studies allows us to make inferences about potential causal association between a risk factor and lung cancer. A risk factor is considered to be causal when the statistical association between the risk factor and a disease across the body of literature meets specific criteria: (1) correctness of temporality--the exposure or risk factor occurs before the disease; (2) strength of the association-there is a strong association (large relative risk) and the relationship shows a dose-response; (3) specificity of the association the relationship is unique and the risk factor is likely to be necessary or sufficient to produce the disease; (4) consistency

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of the relationship--the relationship between the risk factor and the disease is consistent among studies, regardless of study design; (5) biological plausibility--there is a biologically plausible explanation for the association (sometimes called "coherence").14 In the case of factors identified by analytic studies as being associated with a reduced risk of developing a condition, clinical trials are used to confirm that a relationship is causal. Where a factor is associated with a higher risk, however, it is unethical to conduct a clinical trial. One must, instead, rely totally on the above five criteria for evaluating the body of existing literature and reaching conclusions about the likelihood that an observed association is causal. In the sections below, these factors are considered in discussion of the likelihood of risk factors being causal.

Cigarette Smoking Cigarette smoking is the primary risk factor for lung cancer. The evidence supports the causal nature of this association. The trends and patterns of incidence and mortality and their strong correlation with smoking trends were the first evidence of this link, identified as early as 193915 and confirmed in formal retrospective studies reported in 1950.16-18 By the time the Advisory Committee to the Surgeon General issued its now historic report in 1964, concluding that cigarette smoking is causally related to lung cancer with a magnitude of effect that far outweighs other factors, 14 there were more than 6,000 studies in the worldwide scientific literature on smoking and health. These included some three dozen analytic prospective and retrospective studies on the relationship between smoking and lung cancer. Others documented relationships between smoking and other cancer sites or chronic diseases. After reviewing the available evidence, using the five criteria previously described, the Advisory Committee to the Surgeon General concluded that the evidence met all five criteria. Not only did the risk of developing lung cancer increase with duration of smoking and the number of cigarettes smoked per day, but the risk diminished when smoking was discontinued. ~4 The data on dose-response used a variety of measures, including number of cigarettes smoked daily, age of beginning smoking, depth of inhalation, duration of smoking, and duration of cessation. Regardless of the measure, the relation-

BARBARA G. VALANIS

ship held. Since the report was released, thousands of additional studies conducted worldwide have focused on better quantification of the risk and the specific aspects of smoking behavior and tobacco use which further modify the risk of developing lung cancer. These studies have extended and supported the earlier findings and confirmed that cigarette smoking is also causal in women29 By the time of the 1982 Surgeon General's report, 2° strength of the association between smoking and lung cancer across studies was shown by relative risks ratios ranging from 3.8 to 14.2 in males and from 2.0 to 5.0 among females. By 1986, the relative risk of a woman smoker developing lung cancer had increased by a factor of more than four since the early 1960s and was now comparable to that for men in that earlier period. This increase followed changes over time in female smoking behavior which now more closely resembles that of men (see Fig 2); 51% of men were current smokers in 1965, but only 28.1% were in 1991. Among women, the percent smoking peaked around 1965 at 33.9% and declined to 23.5% in 1991. Changes in smoking prevalence precede changes in lung cancer mortality by about 15 to 20 years. 21,22These data support an appropriate temporal sequence of exposure before disease onset and are supported by consistent findings of elevated lung cancer risk among smokers in prospective studies that compare rates of lung cancer over time for smokers versus non-smokers. On the international front, the World Health Organization is concerned with the rapid increase in smoking rates in developing countries. Of particular concern is smoking in China, a country that accounts for nearly one-third of the entire population of the developing world; cigarette consumption increased there from 500 thousand million in 1978 to 1,400 thousand million in 1987 (one quarter of the world's cigarette consumption) .23 Estimates agree that nearly 70% of Chinese men smoke; estimates for Chinese women range from 2% to 10%, 23,24 raising questions about the causes of the high rate of lung cancer among Chinese women. 25

Aspects of Smoking Behavior Related to Risk Lung cancer risk is modified by four aspects of smoking behavior1: (1) Daily dose of tobacco--Among otherwise similar smokers, there is a direct relationship

LUNG CANCER EPIDEMIOLOGY

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between the daily dose and excess lung cancer risk for both men and women. (2) Duration of smoking--Damage to the lung increases with continuous smoking. Therefore, those who begin to smoke as adolescents and continue to smoke are at the greatest risk of developing lung cancer in adult life. On the positive side, clear and consistent evidence indicates that ceasing to smoke before having cancer, even among people who have been smoking for many years, will decrease most subsequent lifelong risk of tobacco-induced lung-cancer. 25 (3) Form in which tobacco is smoked--Smokers who have used only cigarettes have much higher lung cancer risks than those who have used only pipes and/or cigars, although these latter are not without risk. (4) Type of cigarette--Cigarette manufacturers made substantial modifications in cigarette design and smoke composition, particularly tar reduction, after evidence on risks of cigarette smoking was first established in the 1950s. Not enough time has passed to permit direct comparison of the health effects of lifelong use of modified and unmodified cigarettes. However, in one large cohort study, cigarettes delivering less than 17.6 mg tar were associated with a lower lung cancer risk than those

delivering more than 25.7 mg tar 26 and a number of case-control studies showed a fairly consistent lower lung cancer risk among users of filter cigarettes compared with users of non-filter cigarettes; reductions were as large as 40% to 50%. 27 Decreases in lung cancer rates among populations of continuing smokers who now smoke the same number of these new cigarettes as they had of the old ones provide additional evidence.

Effects of Passive Smoking In 1986, the Surgeon General's report focused on passive smoking (second-hand exposure to tobacco smoke) and presented the conclusion that passive smoking is a cause of disease, including lung cancer, among healthy non-smokers. % The same conclusion was reached by authors of several review articles. 1,2931 Review of 30 studies found that 24 of the 30 studies showed an increased risk of lung cancer. This increased risk, ranging from 1.41 to 2.01, was statistically significant in nine of the studies. The Working Group on Passive Smoking concluded that environmental tobacco smoke is causally associated with lung cancer in non-smoking adults and should be classified as a known human carcinogen. 3~ This conclusion is strengthened by recent data from an autopsy study in Greece, which provided biological evidence of

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statistically significant increases in epithelial, possibly precancerous lesions among non-smoking women married to smokers as opposed to those married to non-smokers. 32

Occupational Risk Factors It has been estimated that 15% of male and 5% of female lung cancers may be caused by occupational exposures. 33 Numerous occupational agents show strong associations with lung cancer occurrence. The occupational exposure that has received the most attention as a risk factor for lung cancer is asbestos. Non-smoking asbestos-exposed workers had a relative risk eight times that of non-asbestos exposed workers. For asbestos-exposed workers who smoked, the relative risk was 45 compared with comparable non-smoking, non-asbestos exposed populations. 34 Epidemiological research has since produced a sufficient body of literature to show that asbestos is a cause of lung cancer; all five of the criteria have been met. This association received wide publicity in the 'sixties' and 'seventies' and led to a decrease in the use of asbestos in many household products. Many asbestos-exposed workers who smoked also stopped smoking because of their extreme risk. For chemical exposures resulting from specific industrial processes, it is difficult to link exposure to lung cancer occurrence, because these are complex processes involving multiple chemicals, including additives and contaminates. Other environmental factors may also affect the amount or type of exposure--eg, temperature, humidity, and ventilation. Nonetheless, ionizing radiation, arsenic, sulfur dioxide, chloromethylethyl (ether), formaldehyde, chromium, polynuclear aromatic hydrocarbons, nickel, silica, man-made fibers, and radon are among the agents identified as showing an association with higher rates of lung cancer. 35,36 These exposures and asbestos involve workers in a variety of industries, including atomic energy, automobile maintenance, smelter and foundry, glass and pottery, insulation, metal material, petroleum, shipyards, spray painting, and uranium mining. Accumulating evidence that cell type of lung cancer varies by occupational group may provide important clues in future investigations and have legal implications when a worker claims that his lung cancer is caused by exposure to a particular occupational environment. For asbestos, ionizing radiation, and some

BARBARA G. VALANIS

chemicals, there is an interaction with cigarette smoking that leads to incremental increases in risk over that from exposure to the substance alone, 37-39 although a recent study of arsenic exposure suggested a weaker effect of arsenic on lung cancer among heavy smokers than among light and medium smokers. 4° Environmental tobacco smoke is an occupational hazard for many occupational groups, particularly those working in poorly ventilated settings where there are many smokers--eg, musicians, food industry servers, stewardesses (no longer on US domestic flights). Other workplaces, such as offices and some industrial settings where chemical exposures occur, have implemented smoke-free workplace policies or installed special ventilation systems to minimize the employees' exposure to smoke. Knowing which occupational groups are at risk for lung cancer can help us identify appropriate control measures that can be applied at the worksite. Such control measures can include containing the chemical or its fumes to eliminate or reduce exposure, prohibiting smoking, requiring use of respiratory protection (respirators, masks), improving ventilation, and rotating employees so that exposure is intermittent rather than constant. Changes in industrial processes that have eliminated or reduced exposures to chloromethyl ethers and nickel compounds have provided evidence of a reduced risk of lung cancer after these changes were implemented. 41 The worksite also offers an important target for smoking-cessation efforts. It is often the only place to reach adult smokers. In one worksite program, 70% of smokers participating in the program reported that they would not seek out other programs for smoking cessation. 41 Creating a worksite social environment that supports cessation, for example, as well as implementing policies restricting smoking in the workplace, may enhance the effectiveness of these cessation programs.

Air Pollution Although lung cancer rates are higher where there is air pollution than where there is not, it is difficult to attribute this to air quality. This is because there are too many methodologic problems that confound existing studies. Air pollution is a complex mixture that varies from place to place and over time. 42 Most of the studies are descriptive

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studies that relate lung cancer rates for cities or regions to their air quality over time. These studies generally do not ascertain the smoking habits of these populations, and have no data on occupational exposures, so it is difficult to attribute associations to air quality rather than to these and other factors that have not been measured. In one of the few studies that attempted to separate the effects of cigarette smoking, occupation, and air pollution, Vena43 found a synergistic relationship between exposure to cigarette smoking and air pollution as measured by suspended particulates. The role of other air pollutants, such as sulfur dioxide, and 3,4 benzopyrene were not examined. Nutrition and Lung Cancer Strong evidence exists that diets high in fruit and vegetables are protective against cancer, particularly lung cancer, 44-46 showing approximately a 50% reduction in risk. 45 Numerous vitamins and minerals have been linked with cancer incidence, including beta-carotene and other carotenoids, natural vitamin A, vitamin E, selenium, vitamin C, calcium, vitamin D, and folic acid. Some have been selected for intervention trials, based on a generic hypothesis that free radicals and excited oxygen species are important to the progression of cancers already initiated and that antioxidants might prevent oxygen radical formation or reduce their concentrations, thus reducing the risk of cancer. 47 Vitamins and minerals can also affect other mechanisms or phenomena related to cancer risk--for example, carcinogen blocking activities of c e l l s ~ b y interfering with DNA binding or repair, modulating hormonal or growth factor activity, or improving immune system response. The vitamins most closely associated with lung cancer are beta-carotene (a naturally occuring vitamin A precursor) and vitamin A and its synthetic and naturally-occurring analogues, the retinoids. Vitamin A deficient lung cancer is particularly associated with squamous cell and small cell carcinoma. 45 Evidence from both in vivo and in vitro laboratory studies supports the biological plausibility of vitamin A and betacarotene as preventive agents. Numerous animal studies have shown these compounds can prevent or reverse chemically-induced pulmonary neoplasia and some studies have shown that substantial reductions in tumor incidence and size can be

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obtained by administering retinoids long after the exposures to cancer-inducing carcinogens. 5,48 Unlike blood levels of carotinoids, blood levels of retinol do not reflect dietary intake under normal conditions and, thus, have failed in epidemiologic studies to show a consistent relationship with lung cancer risk. However, animal studies have provided abundant evidence that retinol and synthetic retinoids are protective against epithelial tumours including those of the lung. 45 These and other evidence focused attention on the potential use of beta-carotene and vitamin A as chemopreventive agents. An effective chemopreventive agent for lung cancer would be a useful adjunct to the national and international efforts to reduce occupational exposures and cigarette smoking. An agent that could prevent the development and/or progression of tumors in persons who already have histories of smoking or occupational exposures are essential, given the millions of men and women worldwide who are current or former smokers and who have had asbestos exposure. Several chemoprevention trials testing betacarotene or vitamin A in prevention of lung cancer were initiated in the 1980s. The Finnish Alphacotopheral/beta-carotene trial (ATBC) tested betacarotene alone, beta-carotene plus vitamin E, and vitamin E alone versus placebo in a smoking population. Results from this trial, reported in 1994 were disappointing. No lower risk of lung cancer was seen for vitamin E, and beta-carotene was associated with an increased risk of developing lung cancer. 49 Two other large trials of betacarotene reported results in 1996--the Physician's Health Study and the Carotene and Retinol Efficacy Trial (CARET) trial. The Physician's health study followed more than 22,000 physicians (primarily non-smokers) for 12 years and found no protective or harmful effect of beta-carotene for lung cancer. 5° The CARET trial tested the combination of beta-carotene and vitamin A (retinyl palmitate) versus placebo in heavy smokers and asbestosexposed workers with a history of smoking and found, as did the ATBC trial, an increased risk of lung cancer among the trial participants who took the active vitamins. 51 While these results were extremely disappointing, they reinforce the importance of not smoking, avoiding risky occupational exposures, and eating diets high in fruits and vegetables to prevent lung cancer.

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Other Risk Factors

Other factors reported to be associated with lung cancer risk include radiation in patients treated for ankylosing spondylitis and atomic bomb survivors in Japan, body mass index (leanness), alcohol consumption, pet birds in the home, and endocrine factors (among women). 42 The extent of available evidence varies for these factors, but none approaches that for the risk factors previously discussed. Because of the higher prevalence of adenocarcinoma among women than men and a significantly increased risk of adenocarcinoma among Chinese women with short menstrual cycles (after adjusting for smoking), there is interest in pursuing further research on reproductive and hormonal risk factors among women. 42 A genetic component in the etiology of lung cancer is also being investigated because of the observation that adenocarcinoma and aveolar cell lung cancer is more common in families with other cancers, acquired immune deficiencies, or heritable lung disorders. 42 FUTURE RESEARCH

With 3 million persons worldwide dying annually from lung cancer attributable to smoking, and with the worst consequences of smoking yet to be seen in most countries, cigarette smoking remains clearly the number one target for public health action to reduce cancer risk in the general

population. Except perhaps for more data to help quantify the risks of passive exposure to cigarette smoke, the epidemiological verdict is in regarding cigarette smoking. Everyone in the medical community has a role to play in the important work of helping smokers to quit and those not smoking to remain non-smokers, countering the best efforts and large expenditures of the cigarette manufacturers. Advances in epidemiologic knowledge for the near future will come, in large part, from the occupational sector,36 where identification of additional carcinogens and data on synergistic reactions with cigarette smoke may be helpful in planning preventive measures. Additional research on air quality is likely to focus on more precisely quantifying the nature and type of air pollutants that contribute to lung cancer risk and monitoring to identify geographical locations where these pollutants are found. Diet and lung cancer, including the question of additional risk associated with beta-carotene administration to smokers, is an area for further investigation. Although smoking cessation will eventually lead to reduced risk of lung cancer for current smokers, the risk does not begin to drop for nearly 10 years after quitting. Thus, chemoprevention remains our best hope for reducing the rates of developing lung cancer in those many individuals who have been exposed to tobacco smoke.

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