Cause Of Lung Cancer Research Articles

Effects of work related confounders on the association between silica exposure and lung cancer: a nested case-control study among Chinese miners and pottery workers

The role of silica in the causation of lung cancer is an ongoing debate. In order to explore whether observed association between silica exposure and lung cancer is confounded by exposure to other occupational carcinogens, we updated a previously nested case-control study among a cohort of male workers in 29 Chinese mines and factories on the basis of an extended follow-up. Five hundred and eleven lung cancer cases and 1,879 matched controls were selected. Exposure to respirable silica as well as relevant occupational confounders were quantitatively assessed based on historical industrial hygiene data. The relationship between exposure to silica and lung cancer was analyzed by conditional logistic regression analysis adjusted for exposure to arsenic, polycyclic aromatic hydrocarbons (PAHs), radon, and smoking. In a crude analysis adjusted for smoking only, a significant trend of increasing risk of lung cancer with exposure to silica was found for tin, iron/copper miners, and pottery workers. But after adjustment for relevant occupational confounders, no relationship between silica and lung cancer can be observed. Instead, there is a significant association between lung cancer mortality and cumulative exposure to inorganic arsenic (OR = 1.86, 95% CI: 1.14, 3.04 for each mg/m(3)-year increase) and carcinogenic PAHs (OR = 1.35, 95% CI: 1.08, 1.69 for each 100 microg/m(3)-year increase). This analysis does not provide any evidence to show that exposure to silica causes lung cancer in the absence of confounding factors.

Decreased Smoking and Lung Cancer Risk

People with histories of minimal or no smoking have markedly reduced risk for lung cancer compared with heavy smokers, but does merely cutting down

Canadian individual risks of radon-induced lung cancer for different exposure profiles.

Indoor radon has been determined to be the second leading cause of lung cancer after tobacco smoking. There is an increasing need among radiation practitioners to have numerical values of lung cancer risks for men and women, ever-smokers and never-smokers exposed to radon in homes. This study evaluates individual risks for the Canadian population exposed to radon in homes at different radon concentrations and for different periods of their lives. Based on the risk model developed recently by U.S. Environmental Protection Agency (EPA), individual risks of radon-induced lung cancers are calculated with Canadian age-specific rates for overall and lung cancer mortalities (1996-2000) as well as the Canadian smoking prevalence data in 2002. Convenient tables of lifetime relative risks are constructed for lifetime exposures and short exposures between any two age intervals from 0 to 110, and for various radon concentrations found in homes from 50 to 1000 Bq/m3. The risk of developing lung cancer from residential radon exposure increases with radon concentration and exposure duration. For short exposure periods, such as 10 or 20 years, risks are higher in middle age groups (30-50) compared especially to the later years. Individuals could lower their risks significantly by reducing radon levels earlier in life. The tables could help radiation protection practitioners to better communicate indoor radon risk to members of the public.

50-Year Findings on Smoking

Fifty years ago, Richard Doll led a study of smoking among British male physicians -- one of the first that clearly linked smoking and lung cancer. Now, Doll and colleagues report long-term mortality data for 34,439 of these physicians. The original 1954 study has been republished with the current one. Men born from 1900 to 1930 who smoked only cigarettes and continued smoking …

Genotoxic effects of carbon black particles, diesel exhaust particles, and urban air particulates and their extracts on a human alveolar epithelial cell line (A549) and a human monocytic cell line (THP-1).

The possible genotoxicity of small particulate matter has been under investigation for the last 10 years. Diesel exhaust particles (DEP) are considered as "probably carcinogenic" (IARC group 2A) and a number of studies show genotoxic effects of urban particulate matter (UPM). Carbon black (CB) is carcinogenic in rats. In this study the cytotoxic and genotoxic potency of these three particle types was investigated by exposing human cells (A549 and THP-1 cell lines) in vitro to CB, DEP (SRM 1650, NIST), and UPM (SRM 1648, NIST) for 48 hr. Cytotoxicity was assessed using the Alamar Blue assay, whereas genotoxicity was assessed using the single-cell gel electrophoresis (comet assay). The particles were characterized with regard to their mean diameter in tissue culture medium (CB 100 nm, DEP 400 nm, UPM 2 microm), their total carbon content (CB 99%, DEP 85%, UPM 15%), and their acid-soluble metal composition (UPM >> CB approximately DEP). The concentrations ranged from 16 ng/ml to 16 microg/ml for cytotoxicity tests and from 16 ng/ml to 1.6 microg/ml for genotoxicity tests. In both assays, paraquat was used as a reference chemical. The CB, DEP, and UPM particles showed no significant cytotoxicity. However, all three particles were able to cause significant DNA damage, although to a different extent in the two cell lines. The genotoxicity of washed particles and dichloromethane extracts was also investigated. In THP-1 cells CB washed particles and DEP extracts caused significant DNA damage. This difference in effect may be related to differences in size, structure, and composition of the particles. These results suggest that CB, DEP, and UPM are able to cause DNA damage and, therefore, may contribute to the causation of lung cancer. More detailed studies on influence of size, structure, and composition of the particles are needed.

Primary prevention, smoking, and smoking cessation: implications for future trends in lung cancer prevention.

Cigarette smoking is the major cause of lung cancer, and most lung cancers have historically occurred among current cigarette smokers or recent quitters. The relative risk of developing lung cancer declines in former smokers to approximately twice that of never smokers after 20 years of cessation, but it remains elevated indefinitely. As an increasing fraction of those who have ever smoked become former smokers, the absolute risk of lung cancer in the population will decline; and an increasing fraction of lung cancer cases will occur among former smokers. Data from the 12-year follow-up of American Cancer Society Cancer Prevention Study I are used to estimate lung cancer death rates for smokers, never smokers, and former smokers by duration of cessation. These estimates are combined with population-based estimates of smoking status by birth cohort to generate models of lung cancer death rates for current and former smokers. Modeled estimates of lung cancer death rates suggest that, in the near future, the majority of lung cancer cases will be occurring among former smokers. Former smokers already have acted on the advice of their physicians to reduce their lung cancer risk; however, they will generate an increasing fraction of the cancers that are seen. Approaches must be developed for these former smokers to alter their risk if lung cancer death rates are going to continue to be affected. Additional primary preventive strategies, including chemoprevention, offer hope to these former smokers, as do secondary preventive efforts, such as screening.

The inherited nature of lung cancer: a pilot study

The role of both primary and secondary cigarette smoke exposure in the causation of lung cancer appears certain. An estimated 90% of lung cancer is attributed to cigarette smoke. Remarkably, however, less then 20% of cigarette smokers develop lung cancer. Investigators have suggested that a genetic predisposition to lung cancer may contribute to familial aggregation of this cancer. To understand the contribution of familial aggregation to this type of cancer and potentially identify individuals and families, which may be important in identifying gene(s) responsible for lung cancer, we developed criteria for identification of high-risk families. We have tested the feasibility and utility of these criteria at three Denver, CO hospitals with very different patient populations. Four hundred eighteen individuals were diagnosed with lung cancer at these three hospitals between 1/1/95 and 8/31/95. Twenty-nine percent of individuals expired prior to the time of initial contact. Family history data were obtained on 182 individuals. To be considered positive (suggesting possible autosomal dominant inheritance of lung cancer), families must have at least two first-degree relatives with lung cancer, one of which must be diagnosed before the age of 55. Seventeen of 182 (9.3%) families in the study population met these criteria. We reviewed the remaining family histories that did not meet the established criteria and identified another 2.3% (5/182) of families had evidence for autosomal dominant transmission of lung cancer. An additional 15% (23/182) of families had histories which could not be classified without further information. This study suggests that at least 11.6% of individuals diagnosed with lung cancer will have a positive family history of lung cancer. Use of the criteria developed for this study may lead to an underestimation of the inherited etiology of lung cancer.

Global perspective of tobacco habits and lung cancer: a lesson for third world countries.

Over the past 50 years, a dominant role of tobacco smoking in lung cancer causation has been demonstrated. Almost three-quarters of the lung cancer cases can be attributed to tobacco smoking. The global variation in lung cancer incidence is thought to be directly proportional to the smoking habits prevalent in that part of the world. Lung cancer shows a greater upward trend in incidence in the USA, in central and Eastern Europe than ever before, especially in females. Japan too has recorded a 10-fold increase in incidence in both sexes since 1975. In India the problem is further compounded by absence of authentic data on time trend. The recent trend of available data suggests a more or less linear trend. At present lung cancer ranks among the top three killers in men in almost every metropolis in India. The highest incidence rate has been recorded in Bombay (14.6/ 100,000) and the lowest in Barshi (2.0/100,000). How much of these can be attributed to smoking cannot be commented on as no case-control or cohort studies have ever been undertaken in India. The situation is more alarming in other developing countries, where there is no authentic data on tobacco use or lung cancer incidences. The relationship between tobacco and cancer is both simple and complex. The majority of the cancer patients are smokers, while the cancer incidence is not proportional among smokers. To explain this, various factors such as type of smoke, duration of smoke, amount of carcinogens, presence of activation and metabolism pathways, and lately genetic environment interaction, have been put forward. It appears that the relationship is more complex than at first thought. In developing countries, it is further compounded by lack of data on usage and dependence of the economies of these countries on tobacco. The situation is alarming, with ever-increasing incidence among women and non-smokers exposed to smoke (passive smokers). Tobacco use has already become an epidemic.

Passive smoking and lung cancer in Chandigarh, India

The aim of this study is to assess the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers, a case-control study among lifetime non-smokers was conducted in Chandigarh, India. Cases consisted of 58 non-smoking histologically confirmed lung cancer patients; two controls for each case were selected, one among other patients admitted to the wards and one among the visitors to hospital patients. Subjects were asked about ETS exposure from different tobacco products in childhood and in adulthood at home, at the work place and in vehicles. Multivariate logistic regression analysis was used to assess the effects of the ETS exposure variables on lung cancer. Exposure to ETS during childhood was strongly associated with lung cancer (odds ratio (OR)=3.9; 95% confidence interval (CI)=1.9–8.2), the effect mostly arising from exposure to cigarettes smoke. The excess risk was observed with either a smoking father or mother. An increasing risk was found with increasing number of smokers and duration of exposure. Restricting the analysis to women produced higher estimates of the risk. No increased risk was found with exposure to a smoking spouse, except for those exposed only to cigarette smoke (OR=5.1; 95% CI=1.5–17). A weak association was seen between lung cancer and ETS exposure at the workplace, which increased with the number of years of exposure. Exposure in vehicles also was detected as a risk factor for lung cancer in non-smokers. This study suggests that ETS exposure may be a strong risk factor for lung cancer also in India, a country with low prevalence of smoking and, therefore, low rates of lung cancer. Other studies need to be conducted in similar settings to confirm the role played by ETS exposure early in life in the causation of lung cancer.

Consensus on Synergism between Cigarette Smoke and Other Environmental Carcinogens in the Causation of Lung Cancer

Consensus on Synergism between Cigarette Smoke and Other Environmental Carcinogens in the Causation of Lung Cancer

The hazards of chrysotile asbestos: a critical review.

Chrysotile, or "white", asbestos is the dominant form of asbestos in international commerce today. It accounts for 99% of current world asbestos production of 2 million tonnes. Chrysotile is an extremely hazardous material. Clinical and epidemiologic studies have established incontrovertibly that chrysotile causes cancer of the lung, malignant mesothelioma of the pleura and peritoneum, cancer of the larynx and certain gastrointestinal cancers. Chrysotile also causes asbestosis, a progressive fibrous disease of the lungs. Risk of these diseases increases with cumulative lifetime exposure to chrysotile and rises also with increasing time interval (latency) since first exposure. Comparative analyses have established that chrysotile is 2 to 4 times less potent than crocidolite asbestos in its ability to cause malignant mesothelioma, but of equal potency of causation of lung cancer. The International Agency for Research on Cancer of the World Health Organization has declared chrysotile asbestos a proven human carcinogen. Sales of chrysotile asbestos have virtually ended in Western Europe and North America, because of widespread recognition of its health hazards. However, asbestos sales remain strong in Japan, across Asia and in developing nations worldwide. The claim has been made that chrysotile asbestos can be used "safely" under "certain conditions" in those nations. That claim is not accurate. The Collegium Ramazzini, an international learned society in environmental and occupational medicine, has called for an immediate worldwide ban on all sales and uses of all forms of asbestos, including chrysotile. The rationale for this ban is threefold: (1) that safer substitute materials are readily available, (2) that "controlled" use of asbestos is not possible, and (3) that the health risks of asbestos are not acceptable in either the industrialized or the newly industrializing nations.

CHEMOPREVENTION OF RESPIRATORY TRACT CANCER

Lung cancer is the leading cause of cancer death in the United States, and advances in therapy have accounted for an improvement in five-year survival in this disease from 9% to 13% over the last three decades. Molecular genetic evidence has confirmed the epidemiologic link between tobacco and lung cancer causation, and has clarified the etiology of the persistent risk of lung cancer development in former smokers. Retinoids have shown promise in aerodigestive cancer chemoprevention, both in the reversal of preneoplastic lesions and in the prevention of second primary cancers. After initial epidemiologic and dietary studies had linked beta-Carotene with cancer risk reduction, large randomized phase III studies of this compound have shown no evidence of benefit and some evidence of heightened lung cancer risk in active smokers on high dose supplemental beta-Carotene. Therefore, careful clinical, epidemiologic, and basic studies of retinoids using intermediate end point markers are necessary to determine the definitive role of these compounds in the chemoprevention of respiratory tract cancer, with a particular focus on former smokers.

Recent data on cancer due to asbestos in Germany: Rosler JA, Woitowitz HJ. Institute and Outpatient Clinic, Occupational and Social Medicine, Justus-Liebig University, Giessen. Med Lav 1995;86:440-8

The Authors evaluate the risk of lung cancer and mesothelioma among asbestos workers in Germany. 3,988 workers (3,372 male and 616 female) were included in the study, which took into consideration the branch of the asbestos industry in which they had worked, the duration of their employment and also their smoking habits. At the end of the 12 year follow-up, 3,315 workers were alive and 673 dead. The analysis of cause of death showed an increased risk of dying from lung cancer and pleural and peritoneal mesothelioma, in men as well as in women. The risk was shown to be greatest among workers in the asbestos textile industry and among insulators. A probable multiplicative effect of asbestos exposure and smoking on lung cancer causation was noted.

Lifestyle, environmental pollution and lung cancer in cities of Liaoning in northeastern China

<h2>Abstract</h2> Several studies were conducted in cities of Liaoning Province, one of the areas of China with heavy concentrations of industry, to investigate the effects of life-style factors and environmental pollutants on lung cancer causation. A case-control study involving 1249 lung cancer patients and 1345 population-based controls was conducted in 1985–1988 in Shenyang, the capital of Liaoning. Cigarette smoking was found to be the principal cause of lung cancer in this population, accounting for 55% of the disease in males and 37% in females. There was also a significant increase in lung cancer risk associated with an overall index of indoor air pollution due to coal-burning emission. The population attributable risk (PAR) for indoor air pollution was 13% for males and 17% for females. Risks were significantly increased for workers in the non-ferrous smelter (odds ratio (OR) = 2.6, 95% CI, 1.3–5.1), chemical and drug manufacturing (OR = 3.0, 95% CI, 1.0–8.0), and the glass and pottery industry (OR = 1.6, 95% CI, 1.0–2.5). Studies in the Anshan Iron-Steel Complex showed a significant excess of lung cancer for workers exposed to a variety of dusts. A standardized proportional mortality ratio (SPMR) study of 8887 deaths during 1980–1989 among male workers of the complex indicated a 37% excess risk of lung cancer compared to residents of the city. A nested case-control study was then conducted in that complex. A total of 610 cases of lung cancer diagnosed during 1987–1993 and 959 randomly selected controls from 196993 active and retired employees of the complex were interviewed. Historical monitoring records for dust and benzo(<i>a</i>)pyrene (B(<i>a</i>)P) were collected from 1956–1992 to calculate cumulative exposure for each person. Results suggested that risks were increased for all occupations in which there was exposure to dusts, with the highest risks seen among coke oven workers (OR = 3.5, 95% CI, 2.0–6.4) and fire-resistant brick makers (OR = 2.9, 95% CI, 1.9–4.4). Significant dose-response patterns between cumulative total dust, cumulative total B(<i>a</i>)P and lung cancer risk were observed. The findings suggest that smoking and environmental pollution combine to account for elevated rates of lung cancer in cities of northeastern China.

Lifestyle, environmental pollution and lung cancer in cities of Liaoning in northeastern China

Several studies were conducted in cities of Liaoning Province, one of the areas of China with heavy concentrations of industry, to investigate the effects of life-style factors and environmental pollutants on lung cancer causation. A case-control study involving 1249 lung cancer patients and 1345 population-based controls was conducted in 1985–1988 in Shenyang, the capital of Liaoning. Cigarette smoking was found to be the principal cause of lung cancer in this population, accounting for 55% of the disease in males and 37% in females. There was also a significant increase in lung cancer risk associated with an overall index of indoor air pollution due to coal-burning emission. The population attributable risk (PAR) for indoor air pollution was 13% for males and 17% for females. Risks were significantly increased for workers in the non-ferrous smelter (odds ratio (OR) = 2.6, 95% CI, 1.3–5.1), chemical and drug manufacturing (OR = 3.0, 95% CI, 1.0–8.0), and the glass and pottery industry (OR = 1.6, 95% CI, 1.0–2.5). Studies in the Anshan Iron-Steel Complex showed a significant excess of lung cancer for workers exposed to a variety of dusts. A standardized proportional mortality ratio (SPMR) study of 8887 deaths during 1980–1989 among male workers of the complex indicated a 37% excess risk of lung cancer compared to residents of the city. A nested case-control study was then conducted in that complex. A total of 610 cases of lung cancer diagnosed during 1987–1993 and 959 randomly selected controls from 196993 active and retired employees of the complex were interviewed. Historical monitoring records for dust and benzo( a)pyrene (B( a)P) were collected from 1956–1992 to calculate cumulative exposure for each person. Results suggested that risks were increased for all occupations in which there was exposure to dusts, with the highest risks seen among coke oven workers (OR = 3.5, 95% CI, 2.0–6.4) and fire-resistant brick makers (OR = 2.9, 95% CI, 1.9–4.4). Significant dose-response patterns between cumulative total dust, cumulative total B( a)P and lung cancer risk were observed. The findings suggest that smoking and environmental pollution combine to account for elevated rates of lung cancer in cities of northeastern China.

A role of aryl hydrocarbon hydroxylase inducibility in susceptibility to lung carcinogenesis

Lung cancer mortality has been increasing rapidly in recent years in Japan and is expected to exceed that of stomach cancer in male Japanese in the near future. Although chronic inhalation of cigarette smoke is a major risk factor for the development of lung cancer, it seems important to examine genetic susceptibility to the disease as well. Aryl hydrocarbon hydroxylase (AHH), a drug-metabolism enzyme, is useful in determining the individual differences in genetic susceptibility to lung carcinogenesis. AHH is a microsomal membrane-bound monooxygenase system located in most tissues of the body. In mice, AHH inducibility is under the control of the Ah locus and certain inbred strains of mice are susceptible to AHH induction by 3-methylcholanthrene treatment (Ah responsive strains), while other strains are not (Ah non-responsive strains). A strong correlation was observed between AHH inducibility and tumor incidence in mice. Since AHH is also responsible for the activation to carcinogens of benzo (a)pyrene and other aromatic hydrocarbons in cigarette smoke, it may also be important in humans in the causation of lung cancer. Kellermann et al. investigated the genetics of AHH in a human population and reported that the inducibility of this enzyme was controlled by a single gene locus with 2 dominant alleles. They classified humans as having low, intermediate, or high inducibility of AHH. In addition, they reported a significant positive correlation between the extent of inducibility and susceptibility to lung cancer. Their claim, however, has been both supported and refuted by subsequent investigators. Recently, a close association between development of lung cancer and three polymorphisms of CYP1A1 caused by the presence or absence of one MspI site in the 3'-flanking region, namely, a predominant homozygote pattern (A), a heterozygote pattern (B) and a homozygous rare allele pattern (C), has been reported. The relationship between AHH inducibility and polymorphisms of CYP1A1 had not been investigated previously. Our study indicated that the genotype of C, very frequent in Kreyberg type I, was closely related to high AHH inducibility. Thus, the relationship between AHH inducibility and lung cancer, suggested by Kellermann et al., is supported by our study. Further studies will be needed to confirm the present results. Identification of smokers who have genetically high susceptibility to lung cancer (pattern C), may become important for the prevention of lung cancer.

Modeling the modification of the risk of radon-induced lung cancer by environmental tobacco smoke.

The presence of environmental tobacco smoke (ETS) in homes has been implicated in the causation of lung cancer. While of interest in its own right, ETS also influences the risk imposed by radon and its decay products. The interaction between radon progeny and ETS alters the exposure, intake, uptake, biokinetics, dosimetry, and radiobiology of those progeny. The present paper details model predictions of the various influences of ETS on these factors in the U.S. population and provides estimates of the resulting change in the risk from average levels of radon progeny. It is predicted that the presence of ETS produces a very small (perhaps unmeasurable) increase in the risk of radiation-induced tracheobronchial cancer in homes with initially very high particle concentrations for both active and never-smokers, but significantly lowers the risk in homes with initially lower particle concentrations for both groups when generation 4 of the lung is considered the target site. For generation 16, the presence of ETS generally increases the radon-induced risk of lung cancer, although the increase should be unmeasurable at high initial particle concentrations. The net effect of ETS on human health is suggested to be a complicated function of the initial housing conditions, the concentration of particles introduced by smoking, the target generation considered, and the smoking status of exposed populations. This situation precludes any simple statements concerning the role of ETS in governing the incidence of lung cancer in a population.

RETRACTED ARTICLE: Personality, stress, smoking, and genetic predisposition as synergistic risk factors for cancer and coronary heart disease

Risk factors for cancer have been found in the past to act synergistically in a number of studies. However, these studies were not always designed to test the hypothesis of synergism, and have sometimes failed to equate for important variables, which might influence the results. The present study tests the hypothesis that psychosocial variables and physical ones (personality/stress, smoking, and genetic predisposition) interact in a synergistic fashion in the causation of lung cancer and coronary heart disease (CHD).

A case-control study of air pollution and tobacco smoking in lung cancer among women in Athens

Background. A case-control study exploring the role of smoking and outdoor air pollution in the causation of lung cancer, by histologic type, in nonsmoking women, was undertaken in Athens between 1987 and 1989. Methods. One hundred one women with lung cancer and 89 comparison women with fractures or other orthopedic conditions, all permanent residents of Greater Athens, were included in the study. Smoking habits were ascertained through interviews, whereas lifetime exposure to air pollution was assessed by linking blindly lifelong residential and employment addresses of all subjects with objectively estimated or presumed air pollution levels. Results. The age-adjusted relative risk and 95% confidence intervals for lung cancer among current smokers compared with nonsmokers was 3.40 (1.75–6.61); it was 7.43 (2.88–19.13) among those smoking for more than 30 years and 7.46 (2.40–23.17) among those smoking more than 20 cigarettes per day. The age-adjusted relative risk was 1.70 (0.75–3.89) for adenocarcinoma and 6.45 (2.73–15.25) for other histologic types of lung cancer; statistically significant dose-response trends were evident for both histologic groups. Air pollution levels were associated with increased risk for lung cancer but the relative risk was small and statistically not significant. However, when both air pollution and duration (or quantity) of tobacco smoking, as well as their interaction, were introduced in a multiple logistic regression model, the interaction term was significant at the suggestive level of 0.10. Conclusion. Whereas there is no effect of air pollution among nonsmokers, the relative risk contrasting extreme quartiles of air pollution among smokers of 30 years duration was 2.23. The interaction was almost exclusively accounted for by the nonadenocarcinoma lung tumors.

Passive smoking and diet in the etiology of lung cancer among non-smokets

A case-control study was undertaken in Athens to explore the role of passive smoking and diet in the causation of lung cancer, by histologic type, in non-smoking women. Among 160 women with lung cancer admitted to one of seven major hospitals in Greater Athens between 1987 and 1989, 154 were interviewed in person; of those interviewed, 91 were life-long non-smokers. Among 160 identified controls with fractures or other orthopedic conditions, 145 were interviewed in person; of those interviewed, 120 were life-long non-smokers. Marriage of a non-smoking woman to a smoker was associated with a relative risk for lung cancer of 2.1 (95% confidence interval [CI] 1.1-4.1); number of cigarettes smoked daily by the husband and years of exposure to husband's smoking were positively, but not significantly, related to lung cancer risk. There was no evidence of any association with exposure to smoking of other household members, and the association with exposure to passive smoking at work was small and not statistically significant. Dietary data collected through a semi-quantitative food-frequency questionnaire indicated that high consumption of fruits was inversely related to the risk of lung cancer (the relative risk between extreme quartiles was 0.27 (CI 0.10-0.74)). Neither vegetables nor any other food group had an additional protective effect; furthermore, the apparent protective effect of vegetables was not due to carotenoid vitamin A content and was only partly explained in terms of vitamin C. The associations of lung cancer risk with passive smoking and reduced fruit intake were independent and did not confound each other.(ABSTRACT TRUNCATED AT 250 WORDS)