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The epidemiology of lung Cancer: An overview
The Epidemiology Of Lung Cancer: An Overview Denise M. Oleske
UNG CANCER is now the leading cause of
L cancer mortality. However, most of these deaths are preventable. Nurses are increasingly in-
volved in the planning and implementation of prevention strategies, and in order to accomplish this goal, an understanding of epidemiology is necessary. Epidemiologic studies give us insight into who is at risk for developing lung cancer and what factors are associated with its occurrence. This knowledge base serves to guide prevention and early detection efforts aimed at eliminating this public health problem. PAl-FERNS AND TRENDS IN THE INCIDENCE AND MORTALITY OF LUNG CANCER
To understand the epidemiology of lung cancer, a closer look at the descriptive patterns derived from morbidity and mortality rates is helpful. When these rates are considered in conjunction with individual and group characteristics, geographic location, and time, more specific patterns of risk factors emerge. Lung cancer is recognized as a worldwide problem that commonly occurs in both sexes and in industrialized as well as in developing nations. (Fig 1). The highest incidence is observed in males in the United Kingdom (89.5 per 100,000 age-adjusted population), l In the United States, the incidence of lung cancer is also high, increasing by 13% between 1973 and 1981. The mortality rate during the same time interval demonstrated a similar trend (Table 1). Since the 1950s, the death rate for men has exceeded that for any other cancer (Fig 2A). While this markedly high mortality among males has been noted for some time, it was only within the last decade that the steep incline in lung cancer mortality was observed among females (Fig 2B). Although the absolute level is not as high as in males, the rate of increase for lung cancer mortality among females has been accelerating more rapidly than in males. It is estimated that in 1987, 136,000 deaths from lung cancer will occur in the United States (92,000 in men and 44,000 in women). Of all cancer deaths in men, 36% will be due to lung cancer and in women, 20% are expected to be due to lung cancer. 3 Racial differences in lung cancer incidence and Seminars in Onco/ogyNursing, Vol 3, No 3 (August), 1987: pp 165-173
mortality are also found (Table 1). Both incidence and mortality rates for lung cancer were higher among whites than nonwhites until around 1960. Since that time the mortality rate for nonwhite males has exceeded that of white males. 2 Smoking has been identified as a contributing factor. Recent studies have shown that the prevalence of smoking among blacks is higher than among whites. 4 Furthermore, the ratio of non filter to filter users is 2.4 among black males but only 1.0 among white males. In addition, blacks are less likely to quit smoking than whites. These variations in exposure to risk factors help explain the differential lung cancer mortality and incidence rates between the races and sexes. Lung cancer mortality and incidence rates may also be influenced by other environmental factors (eg, employment in hazardous workplace, poor nutrition). However, the influence of these upon racial and sex-specific variations independent of smoking requires further study. Devesa and Diamond 5 found a significant inverse association between both income and education and age-adjusted lung cancer incidence rates among white and black males, with the lowest socioeconomic status being associated with the highest rates. 5 Among females, a U-shaped pattern was identified with the higher lung cancer rates being found in the lower and upper income groups, and the lower and higher education groups. This pattern was largely attributable to white females, as the lung cancer incidence and socioeconomic relationships of black females tends to parallel that of the black males. Geographic variation of lung cancer mortality rates is most obvious among white males with increased mortality in the northeast, but the highest rates are clustered along the Gulf of Mexico, particularly in Louisiana, and along the southeast At-
From the Department of Health Systems Management and the Department of Preventive Medicine, Rush-Presbyterian St. Luke's Medical Center, Chicago. Address reprint requests to Denise M. Oleske, PhD, RN, Department of Health Systems Management, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612. © 1987 by Grune & Stratton, Inc. 0749-208118710303-0001505.00/0 165
166
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Fig 1. (A} Age-adjusted incidence rates for lung cancer in 80 different geographic areas on five continents (females). (Reprinted with permission. 1) (B) Age-adjusted incidence rates for lung cancer in 80 different geographic areas on five continents (males). (Reprinted with permission. 1)
lantic coast. The highest lung cancer rates for nonwhite males tend to be in the urban areas of the south. Racial and geographic variations over time among females is minor. 6 Regardless of geographic region, mortality from lung cancer is greater in urban than in rural counties. The rates are lowest in farming areas. Adjusting for demographic influences, the impact of industrial factors upon the geographic variation in lung cancer rates becomes more pronounced. Mortality among white males was elevated in counties with paper, chemical, and petroleum manufacturing industries. To a lesser ex-
tent, counties that have transportation as the predominant industry also have shown excess lung cancer mortality, primarily in communities engaged in shipbuilding. 6 Numerous carcinogens have been found to be associated with these industries including polycyclic aromatic hydrocarbons (present in crude petroleum, coal, tars, and combustion products of most organic materials) asbestos (shipbuilding), low level ionizing radiation (nuclear shipyards), and wood preservatives. 7,8 Variations in the distribution of lung cancer cell type has been demonstrated by autopsy studies, review of pathology materials, and mortality and
EPIDEMIOLOGY OF LUNG CANCER
167
Table 1. Average Annual Age-Adjusted Lung Cancer Incidence and Mortality Rates per 100,000 Population by Race and Sex
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incidence data. 9"~2 Squamous cell carcinoma is overwhelmingly the predominant histologic form among men in all age groups (53.6%), whereas adenocarcinoma (30.6%) is the most common form in women until age 60 after which squamous and small cell types predominate. 9 Studies have shown that regardless of histologic type, over 80% of the men and women who develop lung cancer were smokers. 9 RISK
FACTORS LUNG
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Although risk of disease can be evaluated through incidence and mortality rates, these data can usually only provide us with information on how risk ~,aries in absolute terms and only for broad demographic or geographic categories. Analytic epidemiologic studies are conducted when detailed information is sought concerning disease risk that may be attributable to specific social, behavioral, environmental, or biologic factors. The analytic approach commonly used in cancer epide-
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168
miology to identify risk factors are case-control studies, cohort studies, and clinical trials. Epidemiologists use a combination of these methods to refine knowledge concerning risk factors and to attempt to establish a causal association between the suspect risk factor and the disease under investigation. A risk factor is said to be causal when a statistical association is established between it and the disease under investigation and the criteria for causality (strength, consistency, dose-response,
specificity, temporality, coherence, plausability) are met. The model for this purpose is illustrated with the examination of evidence in the relationship of cigarette smoking and lung cancer. Other risk factors associated with lung cancer are also highlighted.
Cigarette Smoking The primary risk factor associated with lung cancer is cigarette smoking, and the work done to date is said to have established a causal association. The evidence to support this conclusion is summarized herein. Causality is first suggested by trends and patterns of incidence data. Historically, the increased relative risk of lung cancer among smokers as compared to nonsmokers was identified as early as 1939.13 However, it was not until the 1950s when the relationship was statistically confirmed in three independent retrospective studies. 14-16Of the 35 retrospective studies conducted on the relationship of cigarette smoking and lung cancer between 1939 and 1970, 19 demonstrated that the relative risk of lung cancer was over five times greater among smokers than nonsmokers. 17 By the mid-1950s results of prospective studies found the relative risk of lung cancer associated with cigarette smoke ranged from 3.8 to 14.2 in males and 2.0 to 5.0 in females. ~7 Subsequently, other prospective studies in Sweden, Japan, and Canada yielded similar results. 17 Thus, both strength of association and consistency of the association were demonstrated. Dose-response gradients between smoking and lung cancer were discerned in both retrospective and prospective studies. This is illustrated in Table 2 where the relative risk of lung cancer increases with the daily amount of cigarettes smoked. Measures of exposure have included number of cigarettes smoked per day, age at which smoking began, depth of inhalation, duration of smoking,
DENISE M. OLESKE
Table 2. Relative Risk for Smokers and Nonsmokers A m o n g Male Lung Cancer Patients and Matched Control Patients With Other Diseases
Daily Average Cigarettes Smoked
Lung Cancer
None 1-4 5-14 15-24 25-49 50 +
7 55 489 475 293 38
Patients Controls 61 129 570 431 154 12
Relative Risk of Different Categories Smokers to Nonsmokers 1.0 3.7 7.5 9.6 16.6 27.6
The different levels of cigarette smoking are compared with nonsmokers. Data from Wynder et al. 14
and duration of cessation. The specificity of the association has been examined by Hammond and Horn 18 in a prospective study. Death rates from lung cancer were found to be highest among those whose smoking habit consisted only of cigarettes (127.2 per 100,000), followed by pipes only (38.5 per 100,000), and cigars only (13. I per 100,000). In addition, the specificity has also been examined by comparing the ratios of death rates of smokers to that of nonsmokers among the various anatomic sites of cancer. The greatest ratio has consistently been identified for lung cancer. The temporality of the association has been supported in all the major prospective studies done to date on this risk factor. Indirect evidence of a temporal association also exists. Per capita cigarette consumption per adult in 1950 in 20 different countries was correlated with lung cancer death rates in the mid-1970s, representing that generation as it entered middle age (Fig 3), and a strong positive correlation was found. 19 Several studies have demonstrated that changes in smoking prevalence precede changes in lung cancer mortality, usually by about 15 to 20 years. 20,21 The classic evidence in support of coherence is provided by Auerbach et a122 who showed that the amount of cigarette smoking is positively correlated with the frequency and intensity of pathologic changes (loss of cilia, basal cell hyperplasia, presence of atypia) in the epithelial lining of the tracheobronchial tree. Cigarette consumption patterns in the context of lung cancer mortality compared in different populations also supports the coherence of the association. For example,
EPIDEMIOLOGY OF LUNG CANCER
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among Mormons, a religious group that advocates abstention from the use of tobacco, lung cancer incidence is significantly less than in the nonMormon population of the same state. 23 The low lung cancer mortality of Mexican-American women is about half that of Anglo women. 24 This is attributable to the fact that fewer MexicanAmerican women smoke and that those who do smoke, smoke less. Laboratory studies provide evidence for plausability. Over 3,000 chemicals have been identified in tobacco smoke, and a number of these are mutagens and/or carcinogens (including nicotine and benzo(a)pyrene). When smoking habits changed to include a higher use of filter and low tar cigarettes, the incidence of lung cancer decreased by 20%. This was largely due to the reduction of nicotine and tar. However, if a smoker of a low tar, filter-tipped cigarette compensates for this nicotine and tar reduction by increasing the number of cigarettes smoked, the toxicity of tobacco smoke is similar for both nonfiltered and filtered cigarettesY Given the extensive evidence (only some of which was described) on the association between cigarette smoking and lung cancer, the most effective control measure for this public health problem is curtailment of cigarette smoking.
Passive Smokh~g Concern over the health consequences attributable to passive smoking has arisen as there has been a decline in the prevalence of smokers. Table 3 lists the major studies published to date on the risk of lung cancer from passive smokers. Side-
stream smoke contains many of the carcinogens found in inhaled tobacco smoke and it is postulated that greater concentrations of some carcinogenic substances may be present. Current data suggests a positive association between passive smoking and lung cancer. However, interpretation of this association should be done with caution. In the United States, spouses' smoking habits (the standard exposure in these studies) may not be an adequate measure of the total exposure to passive smoking. Workplace passive smoking pollution could make a significant contribution to exposure, particularly among those heavily exposed (eg, barmaids, bartenders, waitresses). Early life exposure may also have some role. Significantly increased levels of urinary cotinine (a stable metabolite of nicotine) has been found in infants whose caretakers smoke. 32 The specific mechanism for health effects of passive smoking still need to be understood.
Role of Nutrition The association between vitamin A deficiency and lung cancer has been identified by a number of investigators throughout the world. 33-36 The identification of this association in both retrospective and prospective epidemiologic studies suggests that this is not a chance finding. In these studies, the relative risk of lung cancer associated with a low vitamin A diet has been found to be as low as 1.0 and as high as 4.8, even after statistical adjustments are made for age, smoking habits, and socioeconomic status. The increased risk has been found for squamous cell and small cell carcinoma in m e n Y The role of this dietary factor in women has not been confirmed. A consumption of a diet low in vitamin A (<7,500 mg/wk or <74,000 IU/mo) and a low blood retinol (<56 I.tg/dL) have been isolated in these studies as specific risk factors. Although there are many sources of vitamin A in our diet, including milk, eggs, and liver, one recommendation for reducing the risk of lung cancer by dietary measures is to encourage the daily consumption of green/yellow vegetables. No other dietary factor to date, including vitamin C, has been found to have a etiologic role in lung cancer.
Occupational Risk Factors With respect to occupation, certain high risk groups have been identified. These are listed in
170
DENISE M. OLESKE
Table 3. Epidemiologic Studies of Involuntary Smoking and Lung Cancer
Reference Hirayamaz6
Tricholpoulos et a127
Garfinke128
Correa et al z9
Sandier et al~
Garfinkel et alzl
Country Japan
Greece (Athens)
United States
Study Type (and Gender) Cohort (women)
Case-control (women)
Cohort (women)
United States (New Orleans)
Case-control (both sexes)
United States (North Carolina)
Case-control (both sexes)
United States
Case-control (women)
Measureof Smoking Exposure Husband Nonsmoker <20 cigarettes ---20 clgarettes Husband Nonsmoker <1 pack :>1 pack Husband Nonsmoker <40 cigarettes ---40 cigarettes Spouse Nonsmoker <40 cigarettes ->40 cigarettes Parents Maternal Smoking Nonsmoker Smoker Paternal Smoking Nonsmoker Smoker Husband Nonsmoker <10 cigarettes 10-19 cigarettes ->20 cigarettes
Relative Risk
1.00 1.60 2.08 1.00 2.40 3.40 1.00 1.37(NS) 1.04(NS) 1.00 1.48 3.11
0.60(NS) 2.90(NS) 1.00(NS) 1.30(NS) 1.00 1.15(NS) 1.08(NS) 2.11(NS)
Results are statistically significant (P < .05) unless otherwise indicated.
Table 4. Specific industrial processes are difficult to incriminate in the etiology of lung cancer due to complex chemical reactions occurring in many workplaces and intervening variables (eg, humidity, temperature, worker fatigue). In addition, workers commonly rotate through different departments within the same plant. Such exposure may contribute to a synergistic effect of unknown magnitude by often unknown carcinogens. Similarly, cigarette smoking in the workplace is also noted to produce a synergistic risk of lung cancer. The synergistic effect of cigarette smoking and occupational environment at high risk for lung cancer has been demonstrated in several worker groups including shipyard workers, asbestos workers, and uranium miners. 55-57 Approximately 35% of the employed female workforce smokes. The highest prevalence is among those working as waitresses, managers, salespersons, machine operators, and in crafts. 12 The prevalence of smoking among nurses has been
reported to be declining in the last few years to approximately 25%. 58 However, this is still nearly twice that which has been reported for physicians. 59 Nurses still need to make progress in reducing their smoking levels if they wish not to be in conflict with their primary role as health care promoters. Recently, evidence has begun to accumulate which suggests that cell type variation exists among some occupational groups. Stayner and Wegman 6° found that squamous cell carcinoma is statistically associated with blue collar jobs, even after adjustments for age and smoking habits are made. Oat cell carcinoma is associated with transportation operators. 6t There does not appear to be any cell type variation unique to asbestos exposure. 62 The epidemiologic relation of specific cell type to occupational exposure is an important area of future investigation and may have legal implications when a worker claims that his lung cancer is due to exposure to a particular occupational en-
171
EPIDEMIOLOGY OF LUNG CANCER Table 4. Occupational Groups Identified as High Risk for Lung Cancer Occupational Group
Suspect Etiologic Agent(s)
Reference
Atomic energy workers Automobile maintenance workers Asbestos workers Chemical workers Chloromethyl ethyl workers Copper smelter workers Gas workers Glass, pottery, and linoleum workers Foundry workers Insecticide workers Insulation workers Nickel workers Metal material workers Petroleum workers
Ionizing radiation Asbestos Asbestos Arsenic, sulfur dioxide Chloromethylethyl (ether) Arsenic Temperature of carbonization Chromium Polynuclear aromatic hydrocarbons Arsenic Asbestos Nickel Not identified Arsenic, polynuclear aromatic hydrocarbons Asbestos Nuclear radiation Chromium Polynuclear aromatic hydrocarbons Radon
Mancuso et al 3~ Nicholson et al zs Selikoff et al ~ Bond et aP1 Figueroa et a142 Lubin et al ¢~ Doll et al ~ Davis et al 4s Gibson et al 4s Davis et al 4s Davis et al 4s Pederson et a147 Hirayama 4s Gottlied et al ~
Shipyard workers Spray painters Steel workers Uranium miners
vironment. Lastly, knowing occupational groups at risk for lung cancer can help identify appropriate control measures at the worksite and guide decision-making regarding the return to work subsequent to a diagnosis of lung cancer. Control measures for the reduction of risk to lung cancer in the workplace include a knowledge of the chemicals being used, no smoking at the work site, rotation of employees from fumed work sites, respiratory protection (masks, respirators, exhaust ventilation, etc), and the maintenance of exposure records by the company. Air Pollution
The study of the relationship between air pollution and lung cancer is wrought with many of the same methodologic issues facing the study of occupation and lung cancer. Previous studies of air pollution as a cause of lung cancer have not considered the smoking status of the population studied or their occupation. Further, because there is typically a higher proportion of urban than rural smokers, it is often difficult to estimate how much of the excess lung cancer in urban areas is actually due to noncigarette-smoking-related factors and indoor pollution (particularly passive smoking). Vena 63 has conducted one of the few attempts to separate and evaluate the effects of air pollution, cigarette smoking, and occupation. A synergistic relationship was identified between exposure to
Blot et al ~° Najarian et al sa Dalager et a152 Blot et a153 BEIR Ills4
cigarette smoking and air pollition. Although the concentration of suspended particulates served as the index of health effects in this study, the role of other suspect urban air pollutants such as sulfur dioxide, 3,4 benzopyrene, as well as size of particulate matter, are topics for future studies. FUTURE RESEARCH
Although over 80% of lung cancer is estimated to be caused by cigarette smoking, many questions still need to be answered. Future epidemiologic investigations are likely to focus on refining knowledge concerning exposure. For example, scientists will continue to probe for the existence of additional carcinogens in the workplace that could be responsible for lung cancer and determine which may act synergistically with cigarette smoke. More precise quantification of the nature and type of air pollutants found in a community as well as passive smoking exposure situations are necessary, particularly to help determine what is the threshold effect for lung cancer given minimal exposure. Efforts to improve the reliability and validity of dietary information, particularly in the identification of usage patterns of food supplements and through an understanding of food preparation practices, are required to explore degrees of protection (or risk) from lung cancer associated with different consumption levels of various nutri-
172
DENISE M. OLESKE
t i o n a l s u b s t a n c e s s u c h as v i t a m i n A . L a s t l y , addit i o n a l clinical trials f o c u s i n g o n n u t r i t i o n i n t e r v e n tions in lung cancer prevention and on new
a t t e m p t s a i m e d at s m o k i n g p r e v e n t i o n m e t h o d s will h e l p e l u c i d a t e t h e role o f dietary a n d b e h a v ioral f a c t o r s in the d e v e l o p m e n t o f l u n g c a n c e r .
REFERENCES
1. Segi M: Cancer Incidence in Five Continents, Vol 3. IARC No. 15, 1977 2. Horm JW, Asire AJ, Young JL Jr, et al (eds): The SEER Program: Cancer Incidence and Mortality in the U.S., 1973-1981. NIH Publication No. 85-1837, PHS, NIH, NCI, Bethesda, MD, 1984 3. Silverberg E, Lubera J: Cancer statistics, 1987. CA 7:2-19, 1987 4. Harris JE: Cigarette smoking among successive birth cohorts of men and women in the US during the 1900-80. JNCI 71:473-479, 1983 5. Devesa SS, Diamond EL: Socioeconomic and racial differences in lung cancer incidence. Am J Epidemiol 118:818831, 1983 6. Blot WJ, Fraumeni JF: Changing patterns of lung cancer in the U.S. Am J Epidemiol 115:664-673, 1982 7. Blot WJ, Fraumeni JF Jr: Geographic patterns of lung cancer: Industrial correlations. Am J Epidemiol 103:539-550, 1976 8. Blot WJ, Brinton LS, Fraumeni JF, et al: Cancer mortality in the US counties with petroleum industries. Science 198:51-53, 1977 9. Greenberg ER, Korson R, Baker J, et al: Incidence of lung cancer by cell type: A population-based study in New Hampshire and Vermont. JNCI 72:559-603, 1984 10. Knudtson KP: The pathologic effects of smoking tobacco on the trachea and bronchial mucosa. Am J Clin Pathol 33:310-317, 1960 11. Haenszel W, Loveland DB, Sirken MG: Lung-cancer mortality as related to residence and smoking histories. I. White males. JNCI 28:947-1001, 1962 12. Stellman S, Stellman J: Women's occupations, smoking, and cancer and other diseases. CA 31:29-34, 1981 13. Muller FH: Tabakmissbrauch and lungencarcinom. [Tobacco abuse and carcinoma of the lung.] Zeitschrift fur Krebsforschung 49:57-84, 1939 14. Wynder EL, Graham EA: Tobacco smoking as a possible etiologic factor in bronchogenic carcinoma. A study of six hundred and eighty-four proved cases. JAMA 143:329-336, 1950 15. Doll R, Hill AB: Smoking and carcinoma of the lung. Preliminary report. Br Med J 2:739-748, 1950 16. Levin ML, Goldstein H, Gemhardt PR: Cancer and Tobacco smoking. A preliminary report. JAMA 143:336-338, 1950 17. US DHHS: The Health Consequences of Smoking: A Report of the Surgeon General. Washington, DC, US Government Printing Office, 1982 18. Hammond EC, Horn D: The relationship between human smoking habits and death rates--a follow-up study of 187,766 men. JAMA 155:1316-1328, 1954 19. Doll R, Peto R: The causes of cancer: Quantitative estimates of avoidable risks of cancer in the US today. JNCI 66:1191-1308, 1981
20. Loeb LA, Ernster VL, Warner KE, et al: Smoking and lung cancer: An overview. Cancer Res 44:5940-5958, 1984 21. Dora HF: Tobacco consumption and mortality from cancer and other disease. Public Health Rep 74:581-593, 1959 22. Auerbach O, Stout AP, Hammond EC, et al: Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med 265:253-267, 1961 23. Lyon JL, Klauber MR, Gardner JW, et al: Cancer incidence in Mormons and non-Mormons in Utah, 1966-1970. CA 33:309-316, 1983 24. Holck SE, Warren CW, Rochart RW, et al: Lung cancer mortality and smoking habits: Mexican-American women. Am J Public Health 72:38-42, 1982 25. DeMarina DM: Genotoxicity of tobacco smoke and tobacco smoke condensate. Mutat Res 114:58-89, 1983 26. Hirayama T: Non-smoking wives of heavy smokers have a higher risk of lung cancer: A study from Japan. Br Med J 282:183-185, 1981 27. Trichopoulos D, Kalandidi A, Sparros L, et al: Lung cancer and passive smoking. Int J Cancer 27:1-4, 1981 28. Garfinkel L: Time trends in lung cancer mortality among nonsmokers and a note on passive smoking. JNCI 66:1061-1066, 1981 29. Correa P, Pickle LW, Fontham E, et al: Passive smoking and lung cancer. Lancet 2:595-597, 1983 30. Sandier DP, Everson RB, Wilcox AT, et al: Cancer risk in adulthood from early life exposure to parents' smoking. Am J Public Health 75:487-492, 1985 31. Garfinkel L, Auerbach O, Joubert L: Involuntary smoking and lung cancer: A case-control study. JNCI 75:463-469, 1985 32. Greenberg RA, Haley NJ, Etzel RA, et al: Measuring the exposure of infants to tobacco smoke: Nicotine and cotiaine in urine and saliva. N Engl J Med 310:1075-1078, 1984 33. Bjelke E: Dietary vitamin A and human lung cancer. Int J Cancer 15:561-565, 1975 34. Hirayama T: Diet and cancer. Nutr Cancer 1:67-81, 1979 35. Shekelle RB, Lepper M, Liv S, et al: Dietary vitamin A and risk of cancer in the Western Electric Study. Lancet 2:1185-1189, 1981 36. Kvale G, Bjelke E, Gart J J: Dietary habits and lung cancer risk. Int J Cancer 31:397-405, 1983 37. Byers T, Vena J, Mettlin C, et al: Dietary vitamin A and lung cancer risk: An analysis by histologic subtypes. Am J Epidemiol 120:769-776, 1984 38. Mancuso TF, Stewart AM, Kneale GW: Analyses of Hartford data: Delayed effects of small doses of radiation delivered at slow dose rates, in Peto R, Schneiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 129-143 39. Nicholson WJ, Perkel G, Selikoff IJ, et al: Cancer from occupational asbestos exposure projections 1980-2000, in Peto R, Schneiderman M (eds): Quantification of Occupational
EPIDEMIOLOGY OF LUNG CANCER
Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 87-108 40. Selikoff IJ, Hammond EC, Siedman H: Mortality experience of insulation workers in the U.S. and Canada. Ann NY Acad Sci 330:91-116, 1979 41. Bond GG, F-lores GH, Shellenberger JB, et ah Nested case-control study of lung cancer among chemical workers. Am J Epidemiol 124:53-66, 1986 42. Figueroa WB, Raszkowki R, Weiss W: Lung cancer in chloromethyl ethyl ether workers. N Engl J Med 288:10961097, 1973 43. LubinJH, Pottern LM, Blot WJ, et ah Respiratory cancer among copper smelter workers: Recent mortality statistics. J Occup Med 23:779-84, 1981 44. Doll R, Vessey MP, Beasley RWR, et ah Mortality of gasworkers-final report of a prospective study. Br J Ind Med 29:394-406, 1972 45. Davis DL, Bridbord K, Sctmeiderman M: Estimating cancer causes: Problems in methodology, production, and trends, in Peto R, Schneiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 285-316 46. Gibson ES, Martin RH, Lockington JN: Lung cancer mortality in a steel foundry. J Occup Med 19:807, 1977 47. Pedersen E, Hogetveit AC, Andersen A: Cancer of respiratory tract among workers at a nickel refinery in Norway. Int J Cancer 12:32-41, 1973 48. Hirayama T: Metal material workers and lung cancer in Japan. Ann NY Acad Sci 271:269-272, 1976 49. Gottlied MS, Carr JK: Mortality studies on lung, pancreas, esophageal, and other cancers in Louisiana, in Pcto R, Schneiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 195-204 50. Blot WJ, Fraumeni JF Jr: Cancer among shipyard workers, in Peto R, Sctmeiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 37-46
173
51. Najarian T, Colton T: Mortality from leukemia and cancer in shipyard nuclear workers. Lancet 1:1018-1019, 1978 52. Dalager NA, Mason TJ, Fraumeni JR, et ah Cancer mortality among workers exposed to zinc chromate paints. J Occup Med 22:25, 1980 53. Blot WJ, Brown LM, Pottern LM, et al: Lung cancer among long-term steel workers. Am J Epidemiol 117:706-716, 1983 54. BEIRIIh Report of the Advisory Committee on the Biological Effects of Ionizing Radiation. Washington, DC, National Academy of Sciences, 1980 55. Blot WS, Harrington JM, Toledo A, et al: Lung cancer after employment in shipyard during World War II. N Engl J Med 299:620-624, 1978 56. Saracci R: Asbestos and lung cancer: An analysis of the epidemiological evidence on the asbestos-smoking interaction. Int J Cancer 20:323-331, 1977 57. Chovil A: The epidemiology of primary lung cancer in uranium miners in Ontario. J Occup Med 23:417-421, 1981 58. Morra M, Knobf M: Comparison of nurses smoking habits: The 1975 DHEW survey of Connecticut nurses, 1981. Public Health Rep 98:553-557, 1983 59. Beuchner J, Perry DK, Scott HD, et ah Cigarette smoking behavior among Rhode Island physicians, 1963-83. Am J Public Health 76:285-286, 1986 60. Stayner LT, Wegman DG: Smoking, occupation, and histopathology of lung cancer: A case-control study with the use of the Third National Cancer Survey. JNCI 70:421-426, 1982 61. Wegman DH, Peters JM: Oat cell cancer in selected occupations: A case-control study. J Occup Med 20:793-796, 1978 62. Churg A: Lung cancer cell type and asbestos exposure. JAMA 253:2984-2985, 1985 63. Vena JE: Air pollution as a risk factor in lung cancer. Am J Epidemiol 116:42-56, 1982
UNG CANCER is now the leading cause of
L cancer mortality. However, most of these deaths are preventable. Nurses are increasingly in-
volved in the planning and implementation of prevention strategies, and in order to accomplish this goal, an understanding of epidemiology is necessary. Epidemiologic studies give us insight into who is at risk for developing lung cancer and what factors are associated with its occurrence. This knowledge base serves to guide prevention and early detection efforts aimed at eliminating this public health problem. PAl-FERNS AND TRENDS IN THE INCIDENCE AND MORTALITY OF LUNG CANCER
To understand the epidemiology of lung cancer, a closer look at the descriptive patterns derived from morbidity and mortality rates is helpful. When these rates are considered in conjunction with individual and group characteristics, geographic location, and time, more specific patterns of risk factors emerge. Lung cancer is recognized as a worldwide problem that commonly occurs in both sexes and in industrialized as well as in developing nations. (Fig 1). The highest incidence is observed in males in the United Kingdom (89.5 per 100,000 age-adjusted population), l In the United States, the incidence of lung cancer is also high, increasing by 13% between 1973 and 1981. The mortality rate during the same time interval demonstrated a similar trend (Table 1). Since the 1950s, the death rate for men has exceeded that for any other cancer (Fig 2A). While this markedly high mortality among males has been noted for some time, it was only within the last decade that the steep incline in lung cancer mortality was observed among females (Fig 2B). Although the absolute level is not as high as in males, the rate of increase for lung cancer mortality among females has been accelerating more rapidly than in males. It is estimated that in 1987, 136,000 deaths from lung cancer will occur in the United States (92,000 in men and 44,000 in women). Of all cancer deaths in men, 36% will be due to lung cancer and in women, 20% are expected to be due to lung cancer. 3 Racial differences in lung cancer incidence and Seminars in Onco/ogyNursing, Vol 3, No 3 (August), 1987: pp 165-173
mortality are also found (Table 1). Both incidence and mortality rates for lung cancer were higher among whites than nonwhites until around 1960. Since that time the mortality rate for nonwhite males has exceeded that of white males. 2 Smoking has been identified as a contributing factor. Recent studies have shown that the prevalence of smoking among blacks is higher than among whites. 4 Furthermore, the ratio of non filter to filter users is 2.4 among black males but only 1.0 among white males. In addition, blacks are less likely to quit smoking than whites. These variations in exposure to risk factors help explain the differential lung cancer mortality and incidence rates between the races and sexes. Lung cancer mortality and incidence rates may also be influenced by other environmental factors (eg, employment in hazardous workplace, poor nutrition). However, the influence of these upon racial and sex-specific variations independent of smoking requires further study. Devesa and Diamond 5 found a significant inverse association between both income and education and age-adjusted lung cancer incidence rates among white and black males, with the lowest socioeconomic status being associated with the highest rates. 5 Among females, a U-shaped pattern was identified with the higher lung cancer rates being found in the lower and upper income groups, and the lower and higher education groups. This pattern was largely attributable to white females, as the lung cancer incidence and socioeconomic relationships of black females tends to parallel that of the black males. Geographic variation of lung cancer mortality rates is most obvious among white males with increased mortality in the northeast, but the highest rates are clustered along the Gulf of Mexico, particularly in Louisiana, and along the southeast At-
From the Department of Health Systems Management and the Department of Preventive Medicine, Rush-Presbyterian St. Luke's Medical Center, Chicago. Address reprint requests to Denise M. Oleske, PhD, RN, Department of Health Systems Management, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612. © 1987 by Grune & Stratton, Inc. 0749-208118710303-0001505.00/0 165
166
DENISE M. OLESKE
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lantic coast. The highest lung cancer rates for nonwhite males tend to be in the urban areas of the south. Racial and geographic variations over time among females is minor. 6 Regardless of geographic region, mortality from lung cancer is greater in urban than in rural counties. The rates are lowest in farming areas. Adjusting for demographic influences, the impact of industrial factors upon the geographic variation in lung cancer rates becomes more pronounced. Mortality among white males was elevated in counties with paper, chemical, and petroleum manufacturing industries. To a lesser ex-
tent, counties that have transportation as the predominant industry also have shown excess lung cancer mortality, primarily in communities engaged in shipbuilding. 6 Numerous carcinogens have been found to be associated with these industries including polycyclic aromatic hydrocarbons (present in crude petroleum, coal, tars, and combustion products of most organic materials) asbestos (shipbuilding), low level ionizing radiation (nuclear shipyards), and wood preservatives. 7,8 Variations in the distribution of lung cancer cell type has been demonstrated by autopsy studies, review of pathology materials, and mortality and
EPIDEMIOLOGY OF LUNG CANCER
167
Table 1. Average Annual Age-Adjusted Lung Cancer Incidence and Mortality Rates per 100,000 Population by Race and Sex
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incidence data. 9"~2 Squamous cell carcinoma is overwhelmingly the predominant histologic form among men in all age groups (53.6%), whereas adenocarcinoma (30.6%) is the most common form in women until age 60 after which squamous and small cell types predominate. 9 Studies have shown that regardless of histologic type, over 80% of the men and women who develop lung cancer were smokers. 9 RISK
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Although risk of disease can be evaluated through incidence and mortality rates, these data can usually only provide us with information on how risk ~,aries in absolute terms and only for broad demographic or geographic categories. Analytic epidemiologic studies are conducted when detailed information is sought concerning disease risk that may be attributable to specific social, behavioral, environmental, or biologic factors. The analytic approach commonly used in cancer epide-
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168
miology to identify risk factors are case-control studies, cohort studies, and clinical trials. Epidemiologists use a combination of these methods to refine knowledge concerning risk factors and to attempt to establish a causal association between the suspect risk factor and the disease under investigation. A risk factor is said to be causal when a statistical association is established between it and the disease under investigation and the criteria for causality (strength, consistency, dose-response,
specificity, temporality, coherence, plausability) are met. The model for this purpose is illustrated with the examination of evidence in the relationship of cigarette smoking and lung cancer. Other risk factors associated with lung cancer are also highlighted.
Cigarette Smoking The primary risk factor associated with lung cancer is cigarette smoking, and the work done to date is said to have established a causal association. The evidence to support this conclusion is summarized herein. Causality is first suggested by trends and patterns of incidence data. Historically, the increased relative risk of lung cancer among smokers as compared to nonsmokers was identified as early as 1939.13 However, it was not until the 1950s when the relationship was statistically confirmed in three independent retrospective studies. 14-16Of the 35 retrospective studies conducted on the relationship of cigarette smoking and lung cancer between 1939 and 1970, 19 demonstrated that the relative risk of lung cancer was over five times greater among smokers than nonsmokers. 17 By the mid-1950s results of prospective studies found the relative risk of lung cancer associated with cigarette smoke ranged from 3.8 to 14.2 in males and 2.0 to 5.0 in females. ~7 Subsequently, other prospective studies in Sweden, Japan, and Canada yielded similar results. 17 Thus, both strength of association and consistency of the association were demonstrated. Dose-response gradients between smoking and lung cancer were discerned in both retrospective and prospective studies. This is illustrated in Table 2 where the relative risk of lung cancer increases with the daily amount of cigarettes smoked. Measures of exposure have included number of cigarettes smoked per day, age at which smoking began, depth of inhalation, duration of smoking,
DENISE M. OLESKE
Table 2. Relative Risk for Smokers and Nonsmokers A m o n g Male Lung Cancer Patients and Matched Control Patients With Other Diseases
Daily Average Cigarettes Smoked
Lung Cancer
None 1-4 5-14 15-24 25-49 50 +
7 55 489 475 293 38
Patients Controls 61 129 570 431 154 12
Relative Risk of Different Categories Smokers to Nonsmokers 1.0 3.7 7.5 9.6 16.6 27.6
The different levels of cigarette smoking are compared with nonsmokers. Data from Wynder et al. 14
and duration of cessation. The specificity of the association has been examined by Hammond and Horn 18 in a prospective study. Death rates from lung cancer were found to be highest among those whose smoking habit consisted only of cigarettes (127.2 per 100,000), followed by pipes only (38.5 per 100,000), and cigars only (13. I per 100,000). In addition, the specificity has also been examined by comparing the ratios of death rates of smokers to that of nonsmokers among the various anatomic sites of cancer. The greatest ratio has consistently been identified for lung cancer. The temporality of the association has been supported in all the major prospective studies done to date on this risk factor. Indirect evidence of a temporal association also exists. Per capita cigarette consumption per adult in 1950 in 20 different countries was correlated with lung cancer death rates in the mid-1970s, representing that generation as it entered middle age (Fig 3), and a strong positive correlation was found. 19 Several studies have demonstrated that changes in smoking prevalence precede changes in lung cancer mortality, usually by about 15 to 20 years. 20,21 The classic evidence in support of coherence is provided by Auerbach et a122 who showed that the amount of cigarette smoking is positively correlated with the frequency and intensity of pathologic changes (loss of cilia, basal cell hyperplasia, presence of atypia) in the epithelial lining of the tracheobronchial tree. Cigarette consumption patterns in the context of lung cancer mortality compared in different populations also supports the coherence of the association. For example,
EPIDEMIOLOGY OF LUNG CANCER
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among Mormons, a religious group that advocates abstention from the use of tobacco, lung cancer incidence is significantly less than in the nonMormon population of the same state. 23 The low lung cancer mortality of Mexican-American women is about half that of Anglo women. 24 This is attributable to the fact that fewer MexicanAmerican women smoke and that those who do smoke, smoke less. Laboratory studies provide evidence for plausability. Over 3,000 chemicals have been identified in tobacco smoke, and a number of these are mutagens and/or carcinogens (including nicotine and benzo(a)pyrene). When smoking habits changed to include a higher use of filter and low tar cigarettes, the incidence of lung cancer decreased by 20%. This was largely due to the reduction of nicotine and tar. However, if a smoker of a low tar, filter-tipped cigarette compensates for this nicotine and tar reduction by increasing the number of cigarettes smoked, the toxicity of tobacco smoke is similar for both nonfiltered and filtered cigarettesY Given the extensive evidence (only some of which was described) on the association between cigarette smoking and lung cancer, the most effective control measure for this public health problem is curtailment of cigarette smoking.
Passive Smokh~g Concern over the health consequences attributable to passive smoking has arisen as there has been a decline in the prevalence of smokers. Table 3 lists the major studies published to date on the risk of lung cancer from passive smokers. Side-
stream smoke contains many of the carcinogens found in inhaled tobacco smoke and it is postulated that greater concentrations of some carcinogenic substances may be present. Current data suggests a positive association between passive smoking and lung cancer. However, interpretation of this association should be done with caution. In the United States, spouses' smoking habits (the standard exposure in these studies) may not be an adequate measure of the total exposure to passive smoking. Workplace passive smoking pollution could make a significant contribution to exposure, particularly among those heavily exposed (eg, barmaids, bartenders, waitresses). Early life exposure may also have some role. Significantly increased levels of urinary cotinine (a stable metabolite of nicotine) has been found in infants whose caretakers smoke. 32 The specific mechanism for health effects of passive smoking still need to be understood.
Role of Nutrition The association between vitamin A deficiency and lung cancer has been identified by a number of investigators throughout the world. 33-36 The identification of this association in both retrospective and prospective epidemiologic studies suggests that this is not a chance finding. In these studies, the relative risk of lung cancer associated with a low vitamin A diet has been found to be as low as 1.0 and as high as 4.8, even after statistical adjustments are made for age, smoking habits, and socioeconomic status. The increased risk has been found for squamous cell and small cell carcinoma in m e n Y The role of this dietary factor in women has not been confirmed. A consumption of a diet low in vitamin A (<7,500 mg/wk or <74,000 IU/mo) and a low blood retinol (<56 I.tg/dL) have been isolated in these studies as specific risk factors. Although there are many sources of vitamin A in our diet, including milk, eggs, and liver, one recommendation for reducing the risk of lung cancer by dietary measures is to encourage the daily consumption of green/yellow vegetables. No other dietary factor to date, including vitamin C, has been found to have a etiologic role in lung cancer.
Occupational Risk Factors With respect to occupation, certain high risk groups have been identified. These are listed in
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DENISE M. OLESKE
Table 3. Epidemiologic Studies of Involuntary Smoking and Lung Cancer
Reference Hirayamaz6
Tricholpoulos et a127
Garfinke128
Correa et al z9
Sandier et al~
Garfinkel et alzl
Country Japan
Greece (Athens)
United States
Study Type (and Gender) Cohort (women)
Case-control (women)
Cohort (women)
United States (New Orleans)
Case-control (both sexes)
United States (North Carolina)
Case-control (both sexes)
United States
Case-control (women)
Measureof Smoking Exposure Husband Nonsmoker <20 cigarettes ---20 clgarettes Husband Nonsmoker <1 pack :>1 pack Husband Nonsmoker <40 cigarettes ---40 cigarettes Spouse Nonsmoker <40 cigarettes ->40 cigarettes Parents Maternal Smoking Nonsmoker Smoker Paternal Smoking Nonsmoker Smoker Husband Nonsmoker <10 cigarettes 10-19 cigarettes ->20 cigarettes
Relative Risk
1.00 1.60 2.08 1.00 2.40 3.40 1.00 1.37(NS) 1.04(NS) 1.00 1.48 3.11
0.60(NS) 2.90(NS) 1.00(NS) 1.30(NS) 1.00 1.15(NS) 1.08(NS) 2.11(NS)
Results are statistically significant (P < .05) unless otherwise indicated.
Table 4. Specific industrial processes are difficult to incriminate in the etiology of lung cancer due to complex chemical reactions occurring in many workplaces and intervening variables (eg, humidity, temperature, worker fatigue). In addition, workers commonly rotate through different departments within the same plant. Such exposure may contribute to a synergistic effect of unknown magnitude by often unknown carcinogens. Similarly, cigarette smoking in the workplace is also noted to produce a synergistic risk of lung cancer. The synergistic effect of cigarette smoking and occupational environment at high risk for lung cancer has been demonstrated in several worker groups including shipyard workers, asbestos workers, and uranium miners. 55-57 Approximately 35% of the employed female workforce smokes. The highest prevalence is among those working as waitresses, managers, salespersons, machine operators, and in crafts. 12 The prevalence of smoking among nurses has been
reported to be declining in the last few years to approximately 25%. 58 However, this is still nearly twice that which has been reported for physicians. 59 Nurses still need to make progress in reducing their smoking levels if they wish not to be in conflict with their primary role as health care promoters. Recently, evidence has begun to accumulate which suggests that cell type variation exists among some occupational groups. Stayner and Wegman 6° found that squamous cell carcinoma is statistically associated with blue collar jobs, even after adjustments for age and smoking habits are made. Oat cell carcinoma is associated with transportation operators. 6t There does not appear to be any cell type variation unique to asbestos exposure. 62 The epidemiologic relation of specific cell type to occupational exposure is an important area of future investigation and may have legal implications when a worker claims that his lung cancer is due to exposure to a particular occupational en-
171
EPIDEMIOLOGY OF LUNG CANCER Table 4. Occupational Groups Identified as High Risk for Lung Cancer Occupational Group
Suspect Etiologic Agent(s)
Reference
Atomic energy workers Automobile maintenance workers Asbestos workers Chemical workers Chloromethyl ethyl workers Copper smelter workers Gas workers Glass, pottery, and linoleum workers Foundry workers Insecticide workers Insulation workers Nickel workers Metal material workers Petroleum workers
Ionizing radiation Asbestos Asbestos Arsenic, sulfur dioxide Chloromethylethyl (ether) Arsenic Temperature of carbonization Chromium Polynuclear aromatic hydrocarbons Arsenic Asbestos Nickel Not identified Arsenic, polynuclear aromatic hydrocarbons Asbestos Nuclear radiation Chromium Polynuclear aromatic hydrocarbons Radon
Mancuso et al 3~ Nicholson et al zs Selikoff et al ~ Bond et aP1 Figueroa et a142 Lubin et al ¢~ Doll et al ~ Davis et al 4s Gibson et al 4s Davis et al 4s Davis et al 4s Pederson et a147 Hirayama 4s Gottlied et al ~
Shipyard workers Spray painters Steel workers Uranium miners
vironment. Lastly, knowing occupational groups at risk for lung cancer can help identify appropriate control measures at the worksite and guide decision-making regarding the return to work subsequent to a diagnosis of lung cancer. Control measures for the reduction of risk to lung cancer in the workplace include a knowledge of the chemicals being used, no smoking at the work site, rotation of employees from fumed work sites, respiratory protection (masks, respirators, exhaust ventilation, etc), and the maintenance of exposure records by the company. Air Pollution
The study of the relationship between air pollution and lung cancer is wrought with many of the same methodologic issues facing the study of occupation and lung cancer. Previous studies of air pollution as a cause of lung cancer have not considered the smoking status of the population studied or their occupation. Further, because there is typically a higher proportion of urban than rural smokers, it is often difficult to estimate how much of the excess lung cancer in urban areas is actually due to noncigarette-smoking-related factors and indoor pollution (particularly passive smoking). Vena 63 has conducted one of the few attempts to separate and evaluate the effects of air pollution, cigarette smoking, and occupation. A synergistic relationship was identified between exposure to
Blot et al ~° Najarian et al sa Dalager et a152 Blot et a153 BEIR Ills4
cigarette smoking and air pollition. Although the concentration of suspended particulates served as the index of health effects in this study, the role of other suspect urban air pollutants such as sulfur dioxide, 3,4 benzopyrene, as well as size of particulate matter, are topics for future studies. FUTURE RESEARCH
Although over 80% of lung cancer is estimated to be caused by cigarette smoking, many questions still need to be answered. Future epidemiologic investigations are likely to focus on refining knowledge concerning exposure. For example, scientists will continue to probe for the existence of additional carcinogens in the workplace that could be responsible for lung cancer and determine which may act synergistically with cigarette smoke. More precise quantification of the nature and type of air pollutants found in a community as well as passive smoking exposure situations are necessary, particularly to help determine what is the threshold effect for lung cancer given minimal exposure. Efforts to improve the reliability and validity of dietary information, particularly in the identification of usage patterns of food supplements and through an understanding of food preparation practices, are required to explore degrees of protection (or risk) from lung cancer associated with different consumption levels of various nutri-
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t i o n a l s u b s t a n c e s s u c h as v i t a m i n A . L a s t l y , addit i o n a l clinical trials f o c u s i n g o n n u t r i t i o n i n t e r v e n tions in lung cancer prevention and on new
a t t e m p t s a i m e d at s m o k i n g p r e v e n t i o n m e t h o d s will h e l p e l u c i d a t e t h e role o f dietary a n d b e h a v ioral f a c t o r s in the d e v e l o p m e n t o f l u n g c a n c e r .
REFERENCES
1. Segi M: Cancer Incidence in Five Continents, Vol 3. IARC No. 15, 1977 2. Horm JW, Asire AJ, Young JL Jr, et al (eds): The SEER Program: Cancer Incidence and Mortality in the U.S., 1973-1981. NIH Publication No. 85-1837, PHS, NIH, NCI, Bethesda, MD, 1984 3. Silverberg E, Lubera J: Cancer statistics, 1987. CA 7:2-19, 1987 4. Harris JE: Cigarette smoking among successive birth cohorts of men and women in the US during the 1900-80. JNCI 71:473-479, 1983 5. Devesa SS, Diamond EL: Socioeconomic and racial differences in lung cancer incidence. Am J Epidemiol 118:818831, 1983 6. Blot WJ, Fraumeni JF: Changing patterns of lung cancer in the U.S. Am J Epidemiol 115:664-673, 1982 7. Blot WJ, Fraumeni JF Jr: Geographic patterns of lung cancer: Industrial correlations. Am J Epidemiol 103:539-550, 1976 8. Blot WJ, Brinton LS, Fraumeni JF, et al: Cancer mortality in the US counties with petroleum industries. Science 198:51-53, 1977 9. Greenberg ER, Korson R, Baker J, et al: Incidence of lung cancer by cell type: A population-based study in New Hampshire and Vermont. JNCI 72:559-603, 1984 10. Knudtson KP: The pathologic effects of smoking tobacco on the trachea and bronchial mucosa. Am J Clin Pathol 33:310-317, 1960 11. Haenszel W, Loveland DB, Sirken MG: Lung-cancer mortality as related to residence and smoking histories. I. White males. JNCI 28:947-1001, 1962 12. Stellman S, Stellman J: Women's occupations, smoking, and cancer and other diseases. CA 31:29-34, 1981 13. Muller FH: Tabakmissbrauch and lungencarcinom. [Tobacco abuse and carcinoma of the lung.] Zeitschrift fur Krebsforschung 49:57-84, 1939 14. Wynder EL, Graham EA: Tobacco smoking as a possible etiologic factor in bronchogenic carcinoma. A study of six hundred and eighty-four proved cases. JAMA 143:329-336, 1950 15. Doll R, Hill AB: Smoking and carcinoma of the lung. Preliminary report. Br Med J 2:739-748, 1950 16. Levin ML, Goldstein H, Gemhardt PR: Cancer and Tobacco smoking. A preliminary report. JAMA 143:336-338, 1950 17. US DHHS: The Health Consequences of Smoking: A Report of the Surgeon General. Washington, DC, US Government Printing Office, 1982 18. Hammond EC, Horn D: The relationship between human smoking habits and death rates--a follow-up study of 187,766 men. JAMA 155:1316-1328, 1954 19. Doll R, Peto R: The causes of cancer: Quantitative estimates of avoidable risks of cancer in the US today. JNCI 66:1191-1308, 1981
20. Loeb LA, Ernster VL, Warner KE, et al: Smoking and lung cancer: An overview. Cancer Res 44:5940-5958, 1984 21. Dora HF: Tobacco consumption and mortality from cancer and other disease. Public Health Rep 74:581-593, 1959 22. Auerbach O, Stout AP, Hammond EC, et al: Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med 265:253-267, 1961 23. Lyon JL, Klauber MR, Gardner JW, et al: Cancer incidence in Mormons and non-Mormons in Utah, 1966-1970. CA 33:309-316, 1983 24. Holck SE, Warren CW, Rochart RW, et al: Lung cancer mortality and smoking habits: Mexican-American women. Am J Public Health 72:38-42, 1982 25. DeMarina DM: Genotoxicity of tobacco smoke and tobacco smoke condensate. Mutat Res 114:58-89, 1983 26. Hirayama T: Non-smoking wives of heavy smokers have a higher risk of lung cancer: A study from Japan. Br Med J 282:183-185, 1981 27. Trichopoulos D, Kalandidi A, Sparros L, et al: Lung cancer and passive smoking. Int J Cancer 27:1-4, 1981 28. Garfinkel L: Time trends in lung cancer mortality among nonsmokers and a note on passive smoking. JNCI 66:1061-1066, 1981 29. Correa P, Pickle LW, Fontham E, et al: Passive smoking and lung cancer. Lancet 2:595-597, 1983 30. Sandier DP, Everson RB, Wilcox AT, et al: Cancer risk in adulthood from early life exposure to parents' smoking. Am J Public Health 75:487-492, 1985 31. Garfinkel L, Auerbach O, Joubert L: Involuntary smoking and lung cancer: A case-control study. JNCI 75:463-469, 1985 32. Greenberg RA, Haley NJ, Etzel RA, et al: Measuring the exposure of infants to tobacco smoke: Nicotine and cotiaine in urine and saliva. N Engl J Med 310:1075-1078, 1984 33. Bjelke E: Dietary vitamin A and human lung cancer. Int J Cancer 15:561-565, 1975 34. Hirayama T: Diet and cancer. Nutr Cancer 1:67-81, 1979 35. Shekelle RB, Lepper M, Liv S, et al: Dietary vitamin A and risk of cancer in the Western Electric Study. Lancet 2:1185-1189, 1981 36. Kvale G, Bjelke E, Gart J J: Dietary habits and lung cancer risk. Int J Cancer 31:397-405, 1983 37. Byers T, Vena J, Mettlin C, et al: Dietary vitamin A and lung cancer risk: An analysis by histologic subtypes. Am J Epidemiol 120:769-776, 1984 38. Mancuso TF, Stewart AM, Kneale GW: Analyses of Hartford data: Delayed effects of small doses of radiation delivered at slow dose rates, in Peto R, Schneiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 129-143 39. Nicholson WJ, Perkel G, Selikoff IJ, et al: Cancer from occupational asbestos exposure projections 1980-2000, in Peto R, Schneiderman M (eds): Quantification of Occupational
EPIDEMIOLOGY OF LUNG CANCER
Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 87-108 40. Selikoff IJ, Hammond EC, Siedman H: Mortality experience of insulation workers in the U.S. and Canada. Ann NY Acad Sci 330:91-116, 1979 41. Bond GG, F-lores GH, Shellenberger JB, et ah Nested case-control study of lung cancer among chemical workers. Am J Epidemiol 124:53-66, 1986 42. Figueroa WB, Raszkowki R, Weiss W: Lung cancer in chloromethyl ethyl ether workers. N Engl J Med 288:10961097, 1973 43. LubinJH, Pottern LM, Blot WJ, et ah Respiratory cancer among copper smelter workers: Recent mortality statistics. J Occup Med 23:779-84, 1981 44. Doll R, Vessey MP, Beasley RWR, et ah Mortality of gasworkers-final report of a prospective study. Br J Ind Med 29:394-406, 1972 45. Davis DL, Bridbord K, Sctmeiderman M: Estimating cancer causes: Problems in methodology, production, and trends, in Peto R, Schneiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 285-316 46. Gibson ES, Martin RH, Lockington JN: Lung cancer mortality in a steel foundry. J Occup Med 19:807, 1977 47. Pedersen E, Hogetveit AC, Andersen A: Cancer of respiratory tract among workers at a nickel refinery in Norway. Int J Cancer 12:32-41, 1973 48. Hirayama T: Metal material workers and lung cancer in Japan. Ann NY Acad Sci 271:269-272, 1976 49. Gottlied MS, Carr JK: Mortality studies on lung, pancreas, esophageal, and other cancers in Louisiana, in Pcto R, Schneiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 195-204 50. Blot WJ, Fraumeni JF Jr: Cancer among shipyard workers, in Peto R, Sctmeiderman M (eds): Quantification of Occupational Cancer. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1981, pp 37-46
173
51. Najarian T, Colton T: Mortality from leukemia and cancer in shipyard nuclear workers. Lancet 1:1018-1019, 1978 52. Dalager NA, Mason TJ, Fraumeni JR, et ah Cancer mortality among workers exposed to zinc chromate paints. J Occup Med 22:25, 1980 53. Blot WJ, Brown LM, Pottern LM, et al: Lung cancer among long-term steel workers. Am J Epidemiol 117:706-716, 1983 54. BEIRIIh Report of the Advisory Committee on the Biological Effects of Ionizing Radiation. Washington, DC, National Academy of Sciences, 1980 55. Blot WS, Harrington JM, Toledo A, et al: Lung cancer after employment in shipyard during World War II. N Engl J Med 299:620-624, 1978 56. Saracci R: Asbestos and lung cancer: An analysis of the epidemiological evidence on the asbestos-smoking interaction. Int J Cancer 20:323-331, 1977 57. Chovil A: The epidemiology of primary lung cancer in uranium miners in Ontario. J Occup Med 23:417-421, 1981 58. Morra M, Knobf M: Comparison of nurses smoking habits: The 1975 DHEW survey of Connecticut nurses, 1981. Public Health Rep 98:553-557, 1983 59. Beuchner J, Perry DK, Scott HD, et ah Cigarette smoking behavior among Rhode Island physicians, 1963-83. Am J Public Health 76:285-286, 1986 60. Stayner LT, Wegman DG: Smoking, occupation, and histopathology of lung cancer: A case-control study with the use of the Third National Cancer Survey. JNCI 70:421-426, 1982 61. Wegman DH, Peters JM: Oat cell cancer in selected occupations: A case-control study. J Occup Med 20:793-796, 1978 62. Churg A: Lung cancer cell type and asbestos exposure. JAMA 253:2984-2985, 1985 63. Vena JE: Air pollution as a risk factor in lung cancer. Am J Epidemiol 116:42-56, 1982