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Background: There is uncertainty regarding the association of occupational exposures with lung cancer. We have studied the association between 52 high-risk job titles and lung cancer incidence in a large prospective study, with more than 200,000 participants followed for more than 6 years and 809 incident cases of lung cancer., Methods: Hazard ratios and 95% confidence intervals were computed by the Cox proportional-hazard regression model, adjusting for country, age, sex, social class, diet, physical activity, and smoking habits. We used a CAREX-based job-exposure matrix to infer exposure to lung carcinogens. False-positive report probability was calculated as a measure of potentially false-positive results., Results: Eighteen occupations, mainly related with agriculture, constructions, and metal processing, were associated with increased risk. In addition, incidence tended to increase with the number of hazardous jobs reported. When the occupations were classified according to the presumed exposure to specific carcinogenic agents, the hazard ratios were 1.5 (95% confidence interval = 1.2-1.9) for asbestos, 1.4 (1.1-1.8) for heavy metals, 1.4 (1.1-1.8) for polycyclic aromatic hydrocarbons, and 1.6 (1.2-2.1) for work-related environmental tobacco smoke. The estimated population attributable risk for employment in at least 1 at-risk job was 16% in men and 12% in women., Conclusions: This large prospective study suggests that exposure to occupational lung carcinogens is still a problem, with such exposures producing moderate to large increases in risk.

Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia)., Patients and Methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR)., Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.

Background: Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution., Methods: We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population., Results: The proportion of lung cancers in never- and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5-7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions., Discussion: We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10-20 ug/m3, whereas levels in Italy are around 30 or 40, or higher).Therefore, further reduction in exposure levels below 30 ug/m3 would correspond to additional lung cancer cases prevented, and our estimate of 5-7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe.

To estimate the relationship between air pollution and lung cancer, a nested case-control study was set up within EPIC (European Prospective Investigation on Cancer and Nutrition). Cases had newly diagnosed lung cancer, accrued after a median follow-up of 7 years among the EPIC ex-smokers (since at least 10 years) and never smokers. Three controls per case were matched. Matching criteria were gender, age (+/-5 years), smoking status, country of recruitment and time elapsed between recruitment and diagnosis. We studied residence in proximity of heavy traffic roads as an indicator of exposure to air pollution. In addition, exposure to air pollutants (NO(2), PM10, SO(2)) was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Cotinine was measured in plasma. We found a nonsignificant association between lung cancer and residence nearby heavy traffic roads (odds ratio = 1.46, 95% confidence interval, CI, 0.89-2.40). Exposure data for single pollutants were available for 197 cases and 556 matched controls. For NO(2) we found an odds ratio of 1.14 (95% CI, 0.78-1.67) for each increment of 10 microg/m(3), and an odds ratio of 1.30 (1.02-1.66) for concentrations greater than 30 microg/m(3). The association with NO(2) did not change after adjustment by cotinine and additional potential confounders, including occupational exposures. No clear association was found with other pollutants.

In cancer patients, plasma often contains mutant DNA released by cancer cells. We have assessed the significance of plasma DNA mutations for subsequent cancer development in healthy subjects in a large longitudinal prospective study. The European Prospective Investigation into Cancer and Nutrition study was analyzed with a nested case-control design. Cases were nonsmokers or ex-smokers for >10 years and newly diagnosed with lung, bladder, or upper aerodigestive tract cancers or leukemia accrued after a median follow-up of 6.3 years. Controls were matched 2:1 for follow-up, age, sex, area of recruitment, and smoking status. KRAS2 mutations were detected by mutant-enriched PCR and sequencing (n = 1,098). TP53 mutations were detected by denaturing high-performance liquid chromatography, temporal temperature gradient electrophoresis, and sequencing (n = 550). KRAS2 or TP53 mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up. Among 137 subjects who developed bladder cancer, 5 had KRAS2 mutations [odds ratio (OR), 4.25; 95% confidence interval (95% CI), 1.27-14.15] and 7 had TP53 mutations (OR, 1.81; 95% CI, 0.66-4.97). There was a nonsignificant trend for association between TP53 mutations and bulky adducts in lymphocyte DNA (OR, 2.78; 95% CI, 0.64-12.17). This is the first report of TP53 or KRAS2 mutations in the plasma of healthy subjects in a prospective study, suggesting that KRAS2 mutation is detectable ahead of bladder cancer diagnosis. TP53 mutation may be associated with environmental exposures. These observations have implications for monitoring early steps of carcinogenesis.

Objectives were to investigate prospectively the ability of DNA adducts to predict cancer and to study the determinants of adducts, especially air pollutants. DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) investigation. Cases included newly diagnosed lung cancer (n = 115), upper respiratory cancers (pharynx and larynx; n = 82), bladder cancer (n = 124), leukemia (n = 166), and chronic obstructive pulmonary disease or emphysema deaths (n = 77) accrued after a median follow-up of 7 years among the EPIC former smokers and never-smokers. Three controls per case were matched for questionnaire analyses and two controls per case for laboratory analyses. Matching criteria were gender, age, smoking status, country of recruitment, and follow-up time. Individual exposure to air pollution was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Leukocyte DNA adducts were analyzed blindly using 32P postlabeling technique. Adducts were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88-3.93] when comparing detectable versus nondetectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06-15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24-13.88). A positive association was found between DNA adducts and ozone (O3) concentration. Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. Besides, the association of DNA adduct levels with O3 indicates a possible role for photochemical smog in determining DNA damage.

Intake of fruits and vegetables is thought to protect against the development of lung cancer. However, some recent cohort and case-control studies have shown no protective effect. We have assessed the relation between fruit and vegetable intake and lung cancer incidence in the large prospective investigation on diet and cancer, the European Prospective Investigation Into Cancer and Nutrition (EPIC). We studied data from 478,021 individuals that took part in the EPIC study, who were recruited from 10 European countries and who completed a dietary questionnaire during 1992-1998. Follow-up was to December 1998 or 1999, but for some centres with active follow-up to June 2002. During follow-up, 1,074 participants were reported to have developed lung cancer, of whom 860 were eligible for our analysis. We used the Cox proportional hazard model to determine the effect of fruit and vegetable intake on the incidence of lung cancer. We paid particular attention to adjustment for smoking. Relative risk estimates were obtained using fruit and vegetable intake categorised by sex-specific, cohort-wide quintiles. After adjustment for age, smoking, height, weight and gender, there was a significant inverse association between fruit consumption and lung cancer risk: the hazard ratio for the highest quintile of consumption relative to the lowest being 0.60 (95% Confidence Interval 0.46-0.78), p for trend 0.0099. The association was strongest in the Northern Europe centres, and among current smokers at baseline, and was strengthened when the 293 lung cancers diagnosed in the first 2 years of follow-up were excluded from the analysis. There was no association between vegetable consumption or vegetable subtypes and lung cancer risk. The findings from this analysis can be regarded as re-enforcing recommendations with regard to enhanced fruit consumption for populations. However, the effect is likely to be small compared to smoking cessation., (Copyright 2003 Wiley-Liss, Inc.)

A total of 281 male lung-cancer patients were identified from the hospital cancer registry in the Regional Cancer Centre in Trivandrum. The controls were selected from the visitors and patients' bystanders in the hospital. The recruitment of cases and controls started in 1990, and the present study used the cases registered in the first year. The questionnaire administered to cases and controls collected information on tobacco smoking and alcohol habits. Dietary data were collected using a food frequency questionnaire and were analyzed by multiple logistic regression producing odds ratio estimates of the relative risk and deviance chi-squared tests of significance. Analysis was done on the computer package, EGRET. All models included age, education, religion and smoking to adjust for the effect of confounding. Green vegetables and bananas were found to have a protective association with lung cancer. The odds ratio associated with the highest quartile of vegetable consumption compared with the lowest was 0.32 (95% confidence interval 0.13, 0.78). Forward stepwise regression analysis indicated pumpkins and onions as the most consistently significant protective factors. Animal protein foods and dairy products were found to have a predisposing effect on lung cancer in this study. The expected influence of smoking on lung cancer (a considerable increase in risk among smokers) provided evidence of the reliability of the data. In conclusion the results from this study show that diet has a role in lung cancer aetiology, although the association is weak compared to the effects of smoking.

It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer. A collaborative group of population-based cancer registries and major treatment centers carried out a case-control study, in which 98 cases of lung cancer were identified in patients who had survived at least 1 year following a diagnosis of Hodgkin's disease. A total of 259 matched controls were selected from patients with Hodgkin's disease who did not develop subsequent lung cancer, and for both cases and controls detailed information was abstracted from medical records concerning stage and treatment of Hodgkin's disease. Patients treated with chemotherapy alone had about twice the risk of developing lung cancer than those treated by radiotherapy alone or both modalities. There was no increase in risk with cumulative number of cycles of chemotherapy. Among patients treated with radiotherapy alone, there was an increase in risk related to estimated radiation dose to the lung. There was also a strong association between cigarette smoking and the risk of lung cancer. The finding of a higher risk following chemotherapy than following radiotherapy was unexpected, but could not be explained by any identified methodological flaws. A plausible inference from the study is that all forms of Hodgkin's disease therapy are carcinogenic to the lung and that, in particular, chemotherapy is associated with an increase in risk which is at least comparable to and perhaps higher than the risk produced by radiotherapy.

Significant differences in the incidence levels of lung cancer have been observed among major Chinese dialect groups or communities (Kokkien, Teochew and Cantonese) in Singapore. Among males, the incidence rate is highest in the Hokkiens (age-standardized incidence rate per 100,000 persons per year in Hokkien 67.8, Teochew 55.3, Cantonese 54.0) and among females, it is highest in the Cantonese (Hokkien 12.4, Teochew 12.8, Cantonese 27.2). The present investigation was undertaken to determine the incidence rates of each of the main histological types of lung cancer in the Chinese population and to determine whether there are any correlations between histological patterns and the dialect group differentials that may be of aetiological significance. During the period 1968-1972, a total of 1,747 cases of lung cancer (1,285 males and 462 females) were reported to the Singapore Cancer Registry. It proved possible to type the neoplasms histologically in 476 males (37.0%) and 154 females (33.3%). Age-standardized rates by histological type were computed on the assumption that those histologically typed were a representative sample of all lung cancers. This study shows that Hokkien males have a significantly higher incidence rate of epidermoid carcinoma than the other dialect groups (Hokkien 36.1, Teochew 21.1, Cantonese 17.3). The Cantonese females have significantly higher incidence rates of both epidermoid carcinoma (Hokkien 3.7, Teochew 2.3, Cantonese 5.9) and adenocarcinoma (Hokkien 4.6, Teochew 3.6, Cantonese 11.9). Various sources of bias in studied of this type were examined; it is concluded that the differences in the histologic-specific incidence rates of lung cancer among the various Chinese dialect groups in Singapore are real and not artefactual. The significance of these findings in relation to possible aetiological factors is discussed.

A case-control study was undertaken to clarify reasons for a four-fold increased incidence of mesothelioma discovered among white males in coastal Tidewater, Va., from 1972 to 1978. Sixty-one cases were identified. Interviews with next of kin revealed that the excess was linked to employment in area shipyards. Three-fourths of the cases had been employed in the shipbuilding industry, nearly all beginning employment prior to 1950. Most were career employees, but an increased risk was also found among those who worked only temporarily, mainly during World War II, and were reportedly exposed to asbestos. More of the cases than controls were pipecoverers or pipefitters, but cases were reported to work in a variety of shipyard trades. Few of the mesothelioma cases were heavy smokers, a trend that may be related in part to the competing risks for fatal diseases caused by the interactions of smoking and asbestos exposure. Information obtained by interview for five of the six white females diagnosed with mesothelioma revealed that the husband of four had been employed in the shipbuilding industry.

The high incidence of lung cancer in Chinese females in Singapore, especially among those belonging to the Cantonese dialect group, and the relatively high rates in Chinese males have been studied by means of interviews of cases and controls. A significant dose-response effect of cigarette smoking was found for all male and female groups, but neither smoking nor any other exposure explains the high incidence of lung cancer observed in Cantonese females who exhibit high rates of adenocarcinoma appraently unrelated to smoking. In general, persons with a low consumption of green vegetables were at higher risk for lung cancer. This finding might be due to an increased susceptibility in the presence of a relative deficiency of vitamin A.