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Objective: Despite the implementation of the WHO Framework Convention on Tobacco Control (FCTC) program in Iran, the regulation of second-hand smoke (SHS) exposure-an often-overlooked hazard-, still requires improvement. We employed a multi-center case-control study to investigate the association between exposure to secondhand smoke (SHS) from various tobacco products (cigarettes, water-pipes, pipes, and chopogh), opium use, and the risk of lung cancer., Method: We included 627 lung cancer cases and 3477 controls. Exposure to SHS tobacco and SHS opium was collected through a questionnaire. We used mixed-model logistic regressions to estimate odds ratios (ORs) and 95% confidence intervals (CI)., Result: Among the overall population exposed to second-hand tobacco smoke (SHTS), the odds ratio (OR) compared to those never exposed was 1.35 (95% CI: 1.08-1.71). Never smokers who were ever exposed to second-hand tobacco smoke (SHTS) had 1.69-fold risk of lung cancer compared to those who were never exposed (95% CI: 1.13-2.52). Exposure to SHTS between 2-3 per day (OR = 2.27, 95% CI: 1.13-4.53) and more than three hours per day (OR = 2.29, 95% CI: 1.20-4.37) can increase the risk of lung cancer compared with the no exposure group (P-trend <0.01). We did not observe any association between exposure to second-hand opium smoke (SHOS) and the risk of lung cancer, either in the overall population or among never-smokers., Conclusion: Our study estimates the impact of second-hand tobacco smoke (SHTS) on lung cancer risk in both the overall population and never-smokers. Additional studies are required to evaluate the association between exposure to second-hand smoke from opium and other type of tobacco, including water-pipe and the risk of lung cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lotfi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern., Study Design: Multicentre case-control study., Methods: This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users., Results: The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0-1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4-3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8-4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3-2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9-4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1-2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2-2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5)., Conclusions: Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Introduction: Professional visual artists constitute a heterogeneous vocational group, including, but not limited to painters, photographers, textile artists, and sculptors who may face exposure to workplace hazardous substances and lifestyle factors that may contribute to the development of selected cancers. The objective of this registry-based cohort study was to assess the cancer incidence among Nordic visual artists., Materials and Methods: This study is based on data from the Nordic Occupational Cancer (NOCCA) project that combines census data of 15 million people from all Nordic countries and cancer registries from 1961 to 2005. For the present study we selected a cohort of visual artists from Finland, Iceland, Norway, and Sweden. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates., Results: In male visual artists, there were statistically significant excesses in cancers of the tongue (SIR 2.91, 95% confidence interval 1.74-4.55), oral cavity (2.09, 1.26-3.27), pharynx (2.18, 1.45--3.15), testis (1.91, 1.11-3.05), renal pelvis (2.48, 1.42-4.03) and bladder (1.33, 1.14-1.55). The risk was significantly decreased for cancers of the lip (0.45, 0.18-0.93) and stomach (0.65, 0.50-0.84). In female visual artists, the only significantly increased risk was observed for breast cancer (1.29, 1.13-1.48) and the only significantly decreased risk for stomach cancer (0.43, 0.17-0.88). The incidence of lung cancer was close to the population average in both sexes., Conclusions: The non-elevated incidence of lung cancer suggests a similar prevalence of smoking between visual artists and the general population, while the elevated risk of cancers of mouth and pharynx among male visual artists is suggestive of more widespread alcohol drinking. The excess risk of urogenital cancers might be associated with exposure to solvents.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology., (© 2022 UICC.)

Background: Globally, lung cancer is the most frequent occupational cancer, but the risk associated with the occupations or occupational environment in Iran is not clear. We aimed to assess occupations with the risk of lung cancer., Methods: We used the IROPICAN nationwide case-control study data including 658 incident lung cancer cases and 3477 controls. We assessed the risk of lung cancer in relation to ever working in major groups of International Standard Classification of Occupations, high-risk occupations for lung cancer and duration of employment and lung cancer subtype among construction workers and farmers while controlling for cigarette smoking and opium consumption. We used unconditional regression logistic models to estimate ORs for the association between increased lung cancer risk and occupations., Results: We observed elevated ORs for lung cancer in male construction workers (OR=1.4; 95% CI: 1.0 to 1.8), petroleum industry workers (OR=3.2; 95% CI: 1.1 to 9.8), female farmers (OR=2.6; 95% CI: 1.3 to 5.3) and female bakers (OR=5.5; 95% CI: 1.0 to 29.8). A positive trend by the duration of employment was observed for male construction workers (p< 0.001). Increased risk of squamous cell carcinoma was observed in male construction workers (OR=1.9; 95% CI: 1.2 to 3.0) and female farmers (OR=4.3; 95% CI: 1.1 to 17.2), who also experienced an increased risk of adenocarcinoma (OR=3.8; 95% CI: 1.4 to 9.9)., Discussion: Although we observed associations between some occupations and lung cancer consistent with the literature, further studies with larger samples focusing on exposures are needed to better understand the occupational lung cancer burden in Iran., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: While the excess in lung cancer risk among lower socioeconomic status individuals has been widely described, the magnitude of this association across lung cancer subtypes, as well as histotype-related long-term incidence trends, are inconclusively reported., Aims: We explored the variation in the incidence of the three main lung cancer histotypes (i.e. squamous cell carcinoma, small cell carcinoma and adenocarcinoma) by socioeconomic status (SES, i.e. upper and lower white collar, upper and lower blue collar, and farming/forestry/fishing) in the adult population of four Nordic countries (i.e. Sweden, Norway, Finland and Denmark)., Materials & Methods: We have used data from the Nordic Occupational Cancer Study (NOCCA), computing age-standardized incidence rates per 100,000 person-years truncated at ages 50-69 years, by sex, histotype, country and SES, for the period 1971-2005. We estimated relative risks and the corresponding 95% confidence intervals through Poisson regression models, including terms for SES, age, sex and country, as indicated., Results: A clear socioeconomic gradient, with a progressive increase in lung cancer risk as SES level decreases, was observed in all subtypes and in both sexes. Favourable lung cancer incidence trends were seen among men for squamous cell and small cell carcinomas, although for adenocarcinomas rates were increasing everywhere except for Finland. Among women, upward temporal trends were seen in all SES groups and for all subtypes, although rates increased to a greater extent for low, compared to high, SES, especially in Denmark and Norway. Farmers showed comparatively lower risks compared to other SES categories., Discussion: This prospective cohort study shows that substantial socioeconomic inequalities in the incidence of the most important lung cancer histotypes exist in the Nordic Countries, and that these inequalities are on the rise, especially among women., Conclusion: Smoking habits are likely to largely explain the observed social gradient for lung cancer histotypes in both sexes., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Airway micro-aspiration might contribute to the proposed associations between gastroesophageal reflux disease (GERD) and some lung diseases, including lung cancer. This study aimed to examine the hypothesis that antireflux surgery decreases the risk of small cell carcinoma, squamous cell carcinoma and adenocarcinoma of the lung differently depending on their location in relation to micro-aspiration., Methods: Population-based cohort study including patients having undergone antireflux surgery during 1980-2014 in Denmark, Finland, Iceland, Norway or Sweden. Patients having undergone antireflux surgery were compared with two groups: 1) the corresponding background population, by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) and 2) non-operated GERD-patients, by calculating hazard ratios (HRs) with 95% CIs using multivariable Cox regression with adjustment for sex, age, calendar period, country, chronic obstructive pulmonary disease and obesity diagnosis or type 2 diabetes., Results: Among all 812,617 GERD-patients, 46,996 (5.8%) had undergone antireflux surgery. The SIRs were statistically significantly decreased for small cell carcinoma (SIR = 0.57, 95% CI 0.41-0.77) and squamous cell carcinoma (SIR = 0.75, 95% CI 0.60-0.92), but not for adenocarcinoma of the lung (SIR = 0.90, 95% CI 0.76-1.06). The HRs were also below unity for small cell carcinoma (HR = 0.63, 95% CI 0.44-0.90) and squamous cell carcinoma (HR = 0.80, 95% CI 0.62-1.03), but not for adenocarcinoma of the lung (HR = 1.03, 95% CI 0.84-1.26). Analyses restricted to patients with objective GERD (reflux oesophagitis or Barrett's oesophagus) showed similar results., Conclusions: This all-Nordic study indicates that patients who undergo antireflux surgery are at decreased risk of small cell carcinoma and squamous cell carcinoma of the lung, but not of adenocarcinoma of the lung., Competing Interests: Conflict of interest statement Authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Although the link between severe mental illness (SMI) and elevated cancer mortality is well established, few studies have examined lung cancer survival and SMI in detail. Our study compared cancer-specific mortality in patients with lung cancer with and without a history of SMI and analysed whether mortality differences could be explained by cancer stage at presentation, comorbidity or differences in cancer treatment., Methods: We identified patients with their first lung cancer diagnosis in 1990-2013 from the Finnish Cancer Registry, their preceding hospital admissions due to SMI from the Hospital Discharge Register and deaths from the Causes of Death statistics. Competing risk analyses were used to estimate hazard ratios (HRs) for the impact of SMI on mortality., Results: Of the 37,852 lung cancer cases, 12% had a history of SMI. Cancer-specific mortality differences were found between patient groups in some cancer types after controlling for stage at representation and treatment. Men with a history of psychosis had excess mortality risk (HR = 1.24, 1.06-1.45) in squamous cell carcinoma. Similar excess risk was found among women with psychosis in small-cell carcinoma (HR = 1.76, 1.41-2.19) and in squamous cell carcinoma (HR = 1.67, 1.26-2.20) and among women with mood disorders in adenocarcinoma (HR = 1.37, 1.08-1.74). Patient group differences in HRs in five-year mortality did not markedly change from the 1990s., Conclusions: We found elevated cancer-specific mortality among persons with a history of SMI. Collaboration between patients, mental healthcare professionals and oncological teams is needed to reduce the mortality gap between patients with cancer with and without SMI., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Although the primary cause of lung cancer is smoking, a considerable proportion of all lung cancers occur in never smokers. Gender influences the risk and characteristics of lung cancer and women are overrepresented among never smokers with the disease. Young age at onset and lack of established environmental risk factors suggest genetic predisposition. In this study, we used population-based sampling of young patients to discover candidate predisposition variants for lung adenocarcinoma in never-smoking women., Materials and Methods: We employed archival normal tissue material from 21 never-smoker women who had been diagnosed with lung adenocarcinoma before the age of 45, and exome sequenced their germline DNA., Results and Conclusion: Potentially pathogenic variants were found in eight Cancer Gene Census germline genes: BRCA1, BRCA2, ERCC4, EXT1, HNF1 A, PTCH1, SMARCB1 and TP53. The variants in TP53, BRCA1, and BRCA2 are likely to have contributed to the early onset lung cancer in the respective patients (3/21 or 14%). This supports the notion that lung adenocarcinoma can be a component of certain cancer predisposition syndromes. Fifteen genes displayed potentially pathogenic mutations in at least two patients: ABCC10, ATP7B, CACNA1S, CFTR, CLIP4, COL6A1, COL6A6, GCN1, GJB6, RYR1, SCN7A, SEC24A, SP100, TTN and USH2A. Four patients showed a mutation in COL6A1, three in CLIP4 and two in the rest of the genes. Some of these candidate genes may explain a subset of female lung adenocarcinoma., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI, 2.47-7.60), the 1990s: 3.17 (95%CI, 2.70-3.71), to the 2000s: 1.76 (95%CI, 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0-12.9-7.53, and for nonmelanoma skin cancer 80.0-29.7-10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status., Methods: Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time-to-event analyses accounting for censoring and competing risk of death to estimate incidence, concordance risk and heritability of liability to develop lung cancer by smoking status., Results: During a median of 28.5 years of follow-up, we recorded 1508 incident lung cancers. Of the 30 MZ and 28 DZ pairs concordant for lung cancer, nearly all were current smokers at baseline and only one concordant pair was seen among never smokers. Among ever smokers, the case-wise concordance of lung cancer, that is the risk before a certain age conditional on lung cancer in the co-twin before that age, was significantly increased compared with the cumulative incidence for both MZ and DZ pairs. This ratio, the relative recurrence risk, significantly decreased by age for MZ but was constant for DZ pairs. Heritability of lung cancer was 0.41 (95% CI 0.26 to 0.56) for currently smoking and 0.37 (95% CI 0.25 to 0.49) for ever smoking pairs. Among smoking discordant pairs, the pairwise HR for lung cancer of the ever smoker twin compared to the never smoker co-twin was 5.4 (95% CI 2.1 to 14.0) in MZ pairs and 5.0 (95% CI 3.2 to 7.9) in DZ pairs., Conclusions: The contribution of familial effects appears to decrease by age. The discordant pair analysis confirms that smoking causes lung cancer., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Among workers employed at a nickel refinery in Harjavalta, Finland an increased risk of lung and sinus cancer has been demonstrated in two previous studies. The current study adds 16 more years of follow-up to these studies., Methods: A total of 1,115 persons exposed to nickel and 194 non-exposed workers in the Harjavalta nickel smelter and refinery were followed up for cancer from 1967 to 2011 through the Finnish Cancer Registry., Results: The total number of cancer cases in men was 251 (Standardized incidence ratio (SIR) 1.05) and in women 12 (SIR 1.22). In the most nickel-exposed work site (refinery), there were 14 lung cancers (SIR 2.01) and 3 sinonasal cancers (SIR 26.7, 95%)., Conclusions: It is likely that exposure to nickel compounds is the main reason for elevated nasal cancer risk among the nickel refinery employees and may also contribute to the excess risk of lung cancer. Am. J. Ind. Med. 60:87-95, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Although stainless steel has been produced for more than a hundred years, exposure-related mortality data for production workers are limited., Aims: To describe cause-specific mortality in Finnish ferrochromium and stainless steel workers., Methods: We studied Finnish stainless steel production chain workers employed between 1967 and 2004, from chromite mining to cold rolling of stainless steel, divided into sub-cohorts by production units with specific exposure patterns. We obtained causes of death for the years 1971-2012 from Statistics Finland. We calculated standardized mortality ratios (SMRs) as ratios of observed and expected numbers of deaths based on population mortality rates of the same region., Results: Among 8088 workers studied, overall mortality was significantly decreased (SMR 0.77; 95% confidence interval [CI] 0.70-0.84), largely due to low mortality from diseases of the circulatory system (SMR 0.71; 95% CI 0.61-0.81). In chromite mine, stainless steel melting shop and metallurgical laboratory workers, the SMR for circulatory disease was below 0.4 (SMR 0.33; 95% CI 0.07-0.95, SMR 0.22; 95% CI 0.05-0.65 and SMR 0.16; 95% CI 0.00-0.90, respectively). Mortality from accidents (SMR 0.84; 95% CI 0.67-1.04) and suicides (SMR 0.72; 95% CI 0.56-0.91) was also lower than in the reference population., Conclusions: Working in the Finnish ferrochromium and stainless steel industry appears not to be associated with increased mortality., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine.)

Background and Objective: To analyze the long-term incidence of cancer after the first diagnosis of saccular intracranial aneurysm (sIA) disease., Methods: The Neurosurgery Department of the Kuopio University Hospital (KUH) solely serves a defined Eastern Finnish population. The Kuopio sIA database contains 2,904 consecutive sIA cases from 1980 to 2007, 618 unruptured (170 familial and 448 sporadic) and 2,286 ruptured aneurysmal subarachnoid hemorrhage (aSAH) cases (308 familial and 1,978 sporadic). They were followed for the incidence of cancer (Finnish Cancer Registry) until death (n = 1,176) or until December 31, 2008, giving a total of 26,844 person-years. Their standardized incidence ratios (SIRs) of different cancers were calculated as compared to the corresponding KUH population (year of follow-up, gender, age)., Results: Lung cancer after the first sIA diagnosis occurred in 30 of the 1,340 male patients [SIR = 2.0; 95% confidence interval (CI) = 1.4-2.9], and in 10 of the 1,564 female patients (SIR = 2.6; 95% CI = 1.2-4.7). Poisson regression analysis identified male gender and increasing diameter of the ruptured sIA as independent risk factors for lung cancer, while familial sIA disease, age at aSAH, site of ruptured sIA, or the presence of associated unruptured sIAs had no significant effect., Conclusions: Carriers of the sIA disease have an increased risk of developing lung cancer. Their long-term smoking habits after the sIA diagnosis should be elucidated for preventive purposes., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: To identify biomarkers for cancer in asbestosis patients., Methods: SELDI-TOF and CART were used to identify serum biomarker profiles in 35 asbestosis patients who subsequently developed cancer and 35 did not develop cancer., Results: Three polypeptide peaks (5707.01, 6598.10, and 20,780.70 Da) could predict the development of cancer with 87% sensitivity and 70% specificity. The first two peaks were identified as KIF18A and KIF5A, respectively, and are part of the Kinesin Superfamily of proteins., Conclusions: We identified two Kinesin proteins that can be potentially used as blood biomarkers to identify asbestosis patients at risk of developing lung cancer.

Background: A carcinogenic role of human papillomavirus (HPV) in lung cancer development has been suggested through both clinical and laboratory research during the last two decades., Methods: We did a population-based case-control study nested within the Finnish Maternity Cohort to assess the role of HPV16/18 infections in female lung carcinogenesis. The Finnish Maternity Cohort containing samples from more than 600,000 subjects were linked with nationwide cancer registries (1973-2006). Serum samples were retrieved from 311 women who developed lung cancer and 930 matched controls. The samples were analyzed for antibodies to HPV types 16 and 18 and cotinine (a biomarker of tobacco exposure). Conditional logistic regression-based estimates of odds ratios and 95% confidence intervals adjusted for cotinine levels were calculated., Results: Overall, there was no evidence of increased risk of lung cancer associated with HPV 16 and 18 type-specific infections among nonsmokers and smokers, assessed via cotinine levels., Conclusions: The question of HPV etiologic effect on lung carcinoma deserves further longitudinal studies using different HPV detection methods., Impact: Our results bring new insights into female HPV lung cancer research.

Background: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC., Methods: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC)., Results: Among SCC patients, male SIR=1.58 (95% confidence interval (CI)=1.50-1.66) and female SIR=2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR=1.25, 95% CI=1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men., Conclusion: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC.

Objectives: Exposure to iron fumes and dust and welding fumes is widespread and may increase the risk of lung cancer. The aim of this study was to identify associations between exposure to iron and welding fumes and the incidence of lung cancer among Finnish men., Methods: The cohort of all economically active Finnish men, born in 1906-1945, who participated in the national census in 1970 was followed through the Finnish Cancer Registry for lung cancer cases (N=30,137) during 1971-1995. Their census occupations in 1970 were converted to estimates of cumulative exposure to iron and welding fumes with the Finnish job-exposure matrix on the basis of likelihood, average level, and estimated duration of exposure. Relative risk estimates for categorized cumulative exposure were defined by a Poisson regression, adjusted for smoking, socioeconomic status, and exposure to asbestos and silica dust., Results: The relative risks for lung cancer increased as the cumulative exposure to iron and welding fumes increased. Relative risks in the highest exposure category was 1.35 [95% confidence interval (95% CI) 1.05-1.73] for iron and 1.15 (95% CI 0.90-1.46) for welding fumes. The respective relative risks estimated for squamous-cell carcinoma of the lungs were 1.94 (95% CI 1.35-2.78) and 1.55 (95% CI 1.08-2.24). There was no excess risk of small-cell carcinoma in any exposure category., Conclusions: Occupational exposure to iron and welding fumes was associated with an increase in lung cancer risk, mainly that of squamous-cell carcinoma. The simultaneous exposure to both of these agents and other potential work-related carcinogens complicates the interpretation of the independent roles of the risk factors.

Background: There is inconclusive evidence concerning cancer risks of organic dusts., Aim: The carcinogenic exposures are mainly inhalatory and the authors therefore studied associations between occupational exposure to eight different organic dusts and respiratory cancers in Finland., Methods: The authors followed up a cohort of all economically active Finns born between 1906 and 1945 for 30 million person-years during 1971-95. Incident cases of nasal, laryngeal, and lung cancer and mesotheliomas were identified through a record linkage with the Finnish Cancer Registry. Occupations from the population census in 1970 were converted to exposures to eight organic dusts with a job-exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as a product of prevalence, level, and estimated duration of exposure. Standardised incidence ratios (SIR) and 95% confidence intervals (CI) adjusted for age, period, and social class were calculated for each organic dust using the economically active population as the reference., Results: A total of 20 426 incident cases of respiratory cancer were observed. Slightly increased risk was observed among men exposed to wood dust for nasal cancer (SIR 1.42, 95% CI 0.79 to 2.44). For laryngeal cancer, men exposed to plant dust (mainly grain millers) had a raised SIR in the high exposure class (SIR 3.55, 95% CI 1.30 to 7.72). Men exposed to wood dust had a raised SIR for lung cancer, but only in the low exposure class (SIR 1.11, 95% CI 1.04 to 1.18). Women exposed to wood dust showed an increased SIR for mesotheliomas in the low exposure class (SIR 4.57, 95% CI 1.25 to 11.7) and some excess in the medium exposure category., Conclusions: Exposure to organic dusts is unlikely to be a major risk factor of respiratory cancer. Even exposure to wood dust which is a major exposure in Finland seems to have minor effect for nasal cancer. The authors found suggestive evidence that exposure to grain dust may increase the risk of laryngeal cancer, and some support to the hypothesis that exposure to textile dust, and to plant and animal dust (agricultural dusts) may decrease the risk of lung cancer.

The objective of this study was to determine the site-specific cancer incidence of hypertensive patients and examine the effect of blood pressure-related variables on the risk of cancers with elevated incidence among the hypertensive patients. A record linkage study of Hypertension Register of the North Karelia Project and the Finnish Cancer Registry was conducted. The mean follow-up time was 16 years. A total of 20 529 hypertensive patients were studied. Main outcome measures were standardised incidence ratios and hazard ratios. The overall cancer incidence was close to that of the general population for both men and women. The incidence rate for the kidney cancer was significantly increased in hypertensive patients (standardised incidence ratio 1.34, 95% confidence interval (CI) 1.11-1.60), as well as incidence rates for cancers of pancreas (1.26, 1.02-1.54), and endometrium (1.22, 1.01-1.44) in hypertensive women. The incidence of lung cancer was significantly decreased (0.86, 0.77-0.95). The incidence of liver cancer was elevated with borderline significance (1.36, 0.99-1.82). In Cox regression models, the use of antihypertensive drugs at baseline was a significant predictor of kidney (hazard ratio for use of antihypertensive drugs 1.89, 95% CI 0.96-3.75) and pancreatic cancer (1.78, 0.99-3.22) in women but not in men. The incidence of endometrial cancer or liver cancer was not related to blood pressure levels or the use of antihypertensive drugs. In women, obesity was a significant predictor of cancers of the endometrium, kidney and liver. In conclusion, increased occurrence of some cancer types among hypertensive patients seem to be partly explained by obesity and the use of antihypertensive drugs.

Objectives: The aim of this study was to increase the understanding of the alternative exposure metrics and analysis methods in studies applying job-exposure matrices in analyses of health outcomes, the association between crystalline silica and cancer being used as an example., Methods: Observed and expected numbers of cancer cases during 1971-1995 among Finns born in 1906-1945 were calculated for 393 occupational categories, as defined in the 1970 population census. According to the Finnish Cancer Registry, there were 43 433 lung and 21 444 prostate cancer cases. The Finnish job-exposure matrix (FINJEM) provided estimates of the proportion of exposed persons and the mean level of exposure among the exposed in each occupation., Results: The most comprehensive exposure metric included period- and age-specific estimates of exposure and an estimate of occupational stability, but also remarkably simpler metrics gave significantly elevated estimates of the risk ratio (RR) between 1.36 and 1.50 for lung cancer for occupations with the highest estimated cumulative silica exposure (> or = 10 mg/m3-years), allowing a lag time of 20 years. It proved important to adjust the risk ratios at least for the socioeconomic status and occupational exposure to asbestos. The risk ratios for prostate cancer were close to 1.0 in every model., Conclusions: The results showed that the FINJEM-based analysis was able to replicate the well-known association between exposure to crystalline silica and lung cancer. The FINJEM-based method gives valid results, and it can be used to analyze large sets of register-based data on health outcomes.

Because TP53 mutations can induce an immune response and can occur early in the carcinogenic process for some tumors, p53 autoantibodies may be useful biomarkers for risk of development of cancer. Using banked serum samples from an asbestosis cohort at high risk for cancer, we demonstrate for the first time a statistically significant relationship between p53 autoantibodies and the subsequent development of malignancy (hazard ratio [HR] = 5.5, 95% confidence interval [CI] = 2.8-10.9) with a positive predictive value of 0.76 and an average lead time to diagnosis of 3.5 years. p53 autoantibodies were also significantly associated with p53 alterations in the resultant tumors (kappa = 0.78, p = 0.01).

Objectives: To assess the risk of lung cancer mortality related to occupational exposure to titanium dioxide (TiO2)., Methods: A mortality follow-up study of 15,017 workers (14,331 men) employed in 11 factories producing TiO2 in Europe. Exposure to TiO2 dust was reconstructed for each occupational title; exposure estimates were linked with the occupational history. Observed mortality was compared with national rates, and internal comparisons were based on multivariate Cox regression analysis., Results: The cohort contributed 371,067 person-years of observation (3.3% were lost to follow-up and 0.7% emigrated). 2652 cohort members died during the follow-up, yielding standardized mortality ratios (SMRs) of 0.87 (95% confidence interval [CI] 0.83-0.90) among men and 0.58 (95% CI 0.40-0.82) among women. Among men, the SMR of lung cancer was significantly increased (1.23, 95% CI 1.10-1.38); however, mortality from lung cancer did not increase with duration of employment or estimated cumulative exposure to TiO2 dust. Data on smoking were available for over one third of cohort members. In three countries, the prevalence of smokers was higher among cohort members compared to the national populations., Conclusions: The results of the study do not suggest a carcinogenic effect of TiO2 dust on the human lung.

Background: Studies on engine exhausts and lung cancer have given inconsistent results., Methods: Economically active Finns were followed-up for lung cancer during 1971-95 (33,664 cases). Their Census occupations in 1970 were converted to exposures to diesel and gasoline engine exhausts with a job-exposure matrix. The relative risks (RRs) for cumulative exposure (CE) were defined by Poisson regression, adjusted for smoking, asbestos, and quartz dust exposure, and socioeconomic status., Results: RR for engine exhausts among men did not increase with increasing CE. In women, RR for gasoline engine exhaust was 1.58 (95% CI 1.10-2.26) in the CE-category of 1-99 mg/m(3)-y and 1.66 (1.11-2.50) among those with > or =100 mg/m(3)-y (lag 20 years). With a lag of 10 years RR for the middle/highest diesel exhaust category in women was 1.42 (0.94-2.13)., Conclusions: Occupational exposure to engine exhausts was not consistently associated with lung cancer in this study, possibly due to low exposure levels., (Copyright 2004 Wiley-Liss, Inc.)

Few studies have suggested that elevated blood pressure might be associated with increased risk of lung cancer and that this association might vary according to smoking status. The aim of this study was to assess the effect of blood pressure and its possible interaction with smoking on lung cancer incidence in hypertensive patients. Lung cancer incidence was determined for 7,908 men enrolled in the hypertension register of the North Karelia Project between 1972 and 1988 by record linkage to the nationwide Finnish Cancer Registry. In a Cox regression model, both systolic and diastolic blood pressures were significant predictors of lung cancer, with a 10% increase in risk per 10-mmHg increment in blood pressure. In smokers, the age-adjusted hazard ratio associated with a 10-mmHg increment in diastolic blood pressure was 1.17 (95% confidence interval: 1.05, 1.29), and in nonsmokers it was 0.98 (95% confidence interval: 0.80, 1.16). For systolic blood pressure, these hazard ratios were 1.11 (95% confidence interval: 1.05, 1.17) for smokers and 1.04 (95% confidence interval: 0.95, 1.14) for nonsmokers. These findings suggest that high blood pressure levels are associated with increased risk of lung cancer in smoking, hypertensive men.

Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.

To analyze occupation, expert-evaluated cumulative exposure, and radiographic abnormalities as indicators of asbestos-related cancer risk we followed 16,696 male construction workers for cancer in 1990-2000. We calculated standardized incidence ratios (SIR) in comparison to the Finnish population and relative risks (RR) in a multivariate analysis in comparison to the internal low-exposure category of each indicator. Overall, the risk was increased for mesothelioma (SIR 2.0, 95% CI = 1.0-3.3), but not for lung cancer (SIR 1.1, 95% CI = 0.9-1.2). Radiographic lung fibrosis indicated a 2-fold and a high value of the exposure index a 3-fold RR of lung cancer, while there was no risk among those with pleural plaques. The risk of lung cancer was the highest in insulators (RR 3.7, 95% CI = 1.4-9.9). Occupation, expert-evaluated cumulative exposure, and lung fibrosis are useful indicators of lung cancer risk among construction workers.

Background: Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use., Methods: Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided., Results: Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1-4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment., Conclusions: Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco.

Objectives: To describe the small area system developed in Finland. To illustrate the use of the system with analyses of incidence of lung cancer around an asbestos mine. To compare the performance of different spatial statistical models when applied to sparse data., Methods: In the small area system, cancer and population data are available by sex, age, and socioeconomic status in adjacent "pixels", squares of size 0.5 km x 0.5 km. The study area was partitioned into sub-areas based on estimated exposure. The original data at the pixel level were used in a spatial random field model. For comparison, standardised incidence ratios were estimated, and full bayesian and empirical bayesian models were fitted to aggregated data. Incidence of lung cancer around a former asbestos mine was used as an illustration., Results: The spatial random field model, which has been used in former small area studies, did not converge with present fine resolution data. The number of neighbouring pixels used in smoothing had to be enlarged, and informative distributions for hyperparameters were used to stabilise the unobserved random field. The ordered spatial random field model gave lower estimates than the Poisson model. When one of the three effects of area were fixed, the model gave similar estimates with a narrower interval than the Poisson model., Conclusions: The use of fine resolution data and socioeconomic status as a means of controlling for confounding related to lifestyle is useful when estimating risk of cancer around point sources. However, better statistical methods are needed for spatial modelling of fine resolution data.

The risk of a new primary cancer (NPC) among 77548 Finnish lung cancer patients from 1953 to 1995 was analysed by the histological type of the lung cancer. The relative risks were expressed as standardised incidence ratios (SIR, ratio of the observed and expected numbers of cases). During the follow-up, 1148 NPCs were observed among men and 152 among women. After exclusion of lung cancers, the risk of NPC was elevated in both males (SIR 1.07; 95% confidence interval (CI) 1.00-1.14) and females (SIR 1.21; 95% CI 1.02-1.42). The excess was larger among lung cancer patients with small-cell carcinoma and adenocarcinoma than those with squamous-cell carcinoma. In all major histological groups of lung cancer, significant excess risks were found for cancers of the larynx (SIRs 2.94-4.25), and bladder (SIRs 2.16-2.86). Significantly elevated SIRs were also found for cancers of the stomach (SIR 1.42; 95% CI 1.12-1.76) and kidney (SIR 2.18; 95% CI 1.56-2.97) in squamous-cell carcinoma; for brain tumours (SIR 3.26; 95% CI 1.20-7.09) in small-cell carcinoma; and for cancers of the prostate (SIR 1.68; 95% CI 1.21-2.27) and thyroid (SIR 3.79; 95% CI 1.23-8.85), and brain tumours (SIR 2.34; 95% CI 1.07-4.43) in adenocarcinoma. The risk of contracting NPC at sites where the majority of tumours are adenocarcinomas was elevated among patients with adenocarcinoma of the lung, but not among squamous-cell or small-cell carcinoma patients. In adenocarcinoma, the excess risks of several smoking-related cancers tended to be somewhat lower than those in the other two histological categories. The relative risk of a NPC among patients diagnosed with lung cancer in 1985-1995 was higher than that of patients from earlier periods in all comparable follow-up categories (up to 10 years), possibly suggesting that the increased use of cytostatic drugs had increased the risk of NPC.

Study Objectives: To explore whether the progression of asbestosis correlates with the risk of lung cancer among patients with asbestosis., Design: A group of 85 asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer., Results: Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or ex-smokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity., Conclusions: Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.

Flavonoids are effective antioxidants and, in theory, may provide protection against cancer, although direct human evidence of this is scarce. The relation between the intake of antioxidant flavonoids and subsequent risk of cancer was studied among 9,959 Finnish men and women aged 15-99 years and initially cancer free. Food consumption was estimated by the dietary history method, covering the total habitual diet during the previous year. During a follow-up in 1967-1991, 997 cancer cases and 151 lung cancer cases were diagnosed. An inverse association was observed between the intake of flavonoids and incidence of all sites of cancer combined. The sex- and age-adjusted relative risk of all sites of cancer combined between the highest and lowest quartiles of flavonoid intake was 0.80 (95% confidence interval 0.67-0.96). This association was mainly a result of lung cancer, which presented a corresponding relative risk of 0.54 (95% confidence interval 0.34-0.87). The association between flavonoid intake and lung cancer incidence was not due to the intake of antioxidant vitamins or other potential confounding factors, as adjustment for factors such as smoking and intakes of energy, vitamin E, vitamin C, and beta-carotene did not materially alter the results. The association was strongest in persons under 50 years of age and in nonsmokers with relative risks of 0.33 (95% confidence interval 0.15-0.77) and 0.13 (95% confidence interval 0.03-0.58), respectively. Of the major dietary flavonoid sources, the consumption of apples showed an inverse association with lung cancer incidence, with a relative risk of 0.42 (95% confidence interval 0.23-0.76) after adjustment for the intake of other fruits and vegetables. The results are in line with the hypothesis that flavonoid intake in some circumstances may be involved in the cancer process, resulting in lowered risks.

Although it has been hypothesized that depressive persons have an excess risk of cancer, few prospective data are available. The association between depressiveness and subsequent incidence of lung cancer was studied in the nationally representative Mini-Finland Health Survey. The study population comprised 7,018 adult men and women, free from cancer at the baseline, carried out in 1978-1980. During a 14-year follow-up, 605 cancer cases occurred, of which 70 were male lung cancer patients. Mental problems and disorders were assessed at the baseline examination using standard interview techniques (General Health Questionnaire and Present State Examination). The relative risk of lung cancer between depressive persons and individuals with a normal depressiveness score was 3.32 (95% confidence interval 1.53-7.20). Neither adjustment for the potential confounding factors of age, education, geographic area, smoking, alcohol consumption, body mass index, serum cholesterol, leisure-time exercise, general health, and use of antidepressant medication nor exclusion of cancer cases occurring during the first 4 years of follow-up notably altered the results. There was a strong interaction between depressiveness and smoking. The relative risks of lung cancer between smokers and nonsmokers were 3.38 (95% confidence interval 1.09-10.52) at normal depressiveness score levels and 19.67 (95% confidence interval 2.57-150.7) at strongly elevated levels, respectively. It is possible that depressiveness modifies the effect of smoking on lung cancer risk either by biologic mechanisms or by affecting smoking behavior.

Background: Inhaled radon has been shown to cause lung cancer among underground miners exposed to very high radon concentrations, but the results regarding the effects of residential radon have been conflicting., Purpose: Our aim was to assess the effect of indoor radon exposure on the risk of lung cancer., Methods: To investigate this effect, a nested case-control study was conducted in Finland. The subjects of the study were the 1973 lung cancer case patients (excluding patients with cancers of the pleura) diagnosed from January 1, 1986, until March 31, 1992, within a cohort of Finns residing in the same one-family house from January 1, 1967, or earlier, until the end of 1985 and 2885 control subjects identified from the same cohort and matched by age and sex. In September 1992, a letter was sent to all study subjects or proxy respondents explaining the purpose and methods of the study. After giving informed consent, the study participants were asked to fill out a questionnaire on smoking habits, occupational exposures, and other determinants of lung cancer risk and radon exposure. The odds ratio (OR) of lung cancer was estimated from matched and unmatched logistic regression analyses relative to indoor radon concentration assessed by use of a 12-month measurement with a passive alpha track detector. RESULTS. Five hundred seventeen case-control pairs were used in the matched analysis, and 1055 case subjects and 1544 control subjects were used in the unmatched analysis. The OR of lung cancer for indoor radon exposure obtained from matched analysis was 1.01 (95% confidence interval [CI] = 0.94-1.08) per 2.7 pCi/L (100 Bq m-3) after adjustment for the cigarette smoking status, intensity, duration, and age at commencement of smoking by subjects. For indoor radon concentrations 1.4-2.6, 2.7-5.3, 5.4-10.7, and 10.8-34.5 pCi/L (50-99, 100-199, 200-399, and 400-1277 Bq m-3, respectively), the matched ORs were 1.03 (95% CI = 0.84-1.26), 1.00 (95% CI = 0.78-1.29), 0.91 (95% CI = 0.61-1.35), and 1.15 (95% CI = 0.69-1.93), respectively, relative to the concentration below 1.4 pCi/L (0-49 Bq m-3). The unmatched analysis yielded similar results with somewhat smaller CIs. In the analyses stratified by age, sex, smoking status, or histologic type of lung cancer, no statistically significant indications of increased risk of lung cancer related to indoor radon concentration were observed for any of the subgroups., Conclusions: Our results do not indicate increased risk of lung cancer from indoor radon exposure., Implication: Indoor radon exposure does not appear to be an important cause of lung cancer.

Objective: Studies on experimental animals suggest that inorganic lead is a carcinogen. The purpose of the study was to examine whether occupational exposure to lead increases the risk of cancer., Methods: The study population comprised 20,700 workers who had been biologically monitored for their blood lead (B-Pb) concentrations during 1973-1983. The mortality and cancer incidence rates were followed among the monitored workers and compared with those of the Finnish general population. An internal comparison of the cancer incidence rates was also done between subcohorts formed according to individual B-Pb levels. Questionnaire-based information was also collected on lifetime occupational history and potential confounders, and exposure history was assessed on an individual basis with a nested case-referent design for lung cancer., Results: The internal comparison within the cohort showed a 1.4-fold increase in the overall cancer incidence and a 1.8-fold increase in the incidence of lung cancer among those who had ever had a blood lead level of > or = 1.0 mumol.l-1. In the case-referent study, an increased odds ratio for lung cancer was found for concomitant exposure to lead and engine exhaust. The odds ratio for squamous-cell carcinoma of the lung was increased even when the blood lead level had been slightly elevated. Bias or confounding did not explain the risks., Conclusions: The results suggest that exposure to lead increases the risk of lung cancer. Co-exposure to engine exhaust and lead may be associated with the risk.

The risk of a second cancer among lung cancer patients was investigated using Finnish Cancer Registry data from 1953 to 1989. Among the 36,528 patients with a primary cancer of the lung, 504 new cancers were diagnosed six months or more after the diagnosis of lung cancer, yielding a standardized incidence ratio significantly lower than expected (SIR = 0.81). A significant excess of cancers of the larynx (SIR = 2.10) and urinary bladder (SIR = 1.35) was observed Among lung cancer patients below 60 years of age, the risks of oesophageal cancer (SIR = 2.47) and kidney cancer (SIR = 2.48) were also significantly elevated. The risk of a second cancer among lung cancer patients increased with the length of follow-up, and there was some indication of an excess risk of oesophageal cancer and leukaemia among lung cancer patients subject to radiotherapy.

Cancer incidence during 1953 to 1991 in 811 Finnish silicotic patients diagnosed between 1936 and 1977 was evaluated. In comparison with the general population, excesses were observed for all cancers (standardized incidence ratio, 1.7 [95% confidence interval, 1.4 to 1.9]), all lung cancers (2.9 [2.4 to 3.5]), squamous cell lung cancers (3.3 [2.3 to 4.5]), and skin cancers: melanoma (3.0 [0.8 to 7.6]) and nonmelanoma (2.9 [1.2 to 6.1]). Confounding by tobacco smoking did not explain the lung cancer increment. The consistency of the association between silicosis and lung cancer across a large number of studies suggests that silicosis represents a direct or indirect lung cancer hazard. The skin cancer excess, a relatively novel finding, may be explained either by carcinogens in foundries, or silica-induced lowering of immunocompetence, which would lead to a more pronounced effect of solar ultraviolet radiation.

Bronchial asthma itself or the treatment of asthma may modify the immunological response to cancer. The survival of lung cancer patients with a preceding diagnosis of bronchial asthma was compared with that of non-asthmatic lung cancer patients in Finland during 1970-1989. This was accomplished by linking two nation-wide data registers, the medication reimbursement register and the cancer registry. For 921 out of the 926 asthmatic patients with lung cancer diagnosed after the diagnosis of bronchial asthma, a non-asthmatic referent patient, matching with respect to sex, anatomical site, and histological type of tumour, as well as to age and year of lung cancer diagnosis, was successfully found in the files of the Cancer Registry. Another referent group was formed by using the stage of lung cancer at diagnosis as an extra matching criterion; this search was successful for 895 asthmatic lung cancer patients. The corrected 5-year survival rate of asthmatic lung cancer patients was 8.4% and that of the referent patients, not matched for stage, 9.6%. When stage was included as matching criterion the corresponding rates were 8.5% and 8.1% respectively. None of these differences were significant. The prognosis of asthmatic and non-asthmatic lung cancer patients thus seemed to be similar.

A total of 1,388 workers employed for at least 3 months at a copper/nickel smelter and nickel refinery were followed up for cancer from 1953 to 1987 through the Finnish Cancer Registry. There were 1,339 male and 49 female workers, making a total of 27,130 and 706 person-years, respectively. All of the women worked in the refinery, which opened in 1960, the same year the smelting of nickel began. A total of 67 cancers were diagnosed among the men, the standardized incidence ratio for all cancers being 1.0. No cancer was found among the women (1.8 expected). The risk of cancer among men was analysed according to primary site, exposure to nickel, type of work, years since first exposure and age at diagnosis. In the subcohort of nickel refinery workers, one case of sinonasal cancer was observed, against 0.02 expected, but otherwise no significantly increased risks of cancer were found. In addition to the small size of the cohort, the non-positive finding concerning lung cancer might be related to the relatively low arsenic exposure and, perhaps, to the late commencement of nickel production.

Body mass index (weight/height2) was studied for its prediction of lung cancer in Finnish men examined by the Social Insurance Institution's Mobile Clinic and followed up by the Finnish Cancer Registry. Among 25,994 participants aged 20 to 75 years and free from cancer at the start of the study, 504 lung-cancer cases were diagnosed during a maximum follow-up of 19 years. There was a significant inverse gradient between body mass index and the incidence of lung cancer. This association was not due to confounding by age, smoking, social class, self-perceived general health, history of stress symptoms, chronic cough or chest X-ray findings, although these factors correlated with body mass index and were also significantly predictive of lung cancer. After adjustment for these factors, the relative risks of lung cancer were 1.0, 1.4, 1.5 and 1.8 (p for trend less than 0.001) from the highest to the lowest quartiles of body mass index. The association was noted among current smokers, but it was most obvious among men who had never smoked, the relative risk of lung cancer between the lowest and highest quartiles of body mass index being 7.6 (95% confidence interval = 2.0 to 29.4). The inverse gradient persisted throughout the entire follow-up period, and was most distinct after the first 10 years of follow-up, the relative risks for the quartiles of body mass index being 1.0, 1.9, 2.3 and 2.6 (p less than 0.001). The present study shows that the thinner the man, the more liable he is to develop lung cancer. Leanness or some factor or cluster of factors closely correlated to it, may play an aetiological role in lung cancer.

The relation between the intake of retinoids, carotenoids, vitamin E, vitamin C, and selenium and the subsequent risk of lung cancer was studied among 4,538 initially cancer-free Finnish men aged 20-69 years. During a follow-up of 20 years beginning in 1966-1972, 117 lung cancer cases were diagnosed. Inverse gradients were observed between the intake of carotenoids, vitamin E, and vitamin C and the incidence of lung cancer among nonsmokers, for whom the age-adjusted relative risks of lung cancer in the lowest tertile of intake compared with that in the highest tertile were 2.5 (p value for trend = 0.04), 3.1 (p = 0.12), and 3.1 (p less than 0.01) for the three intakes, respectively. Adjustment for various potential confounding factors did not materially alter the results, and the associations did not seem to be due to preclinical cancer. In the total cohort, there was an inverse association between intake of margarine and fruits and risk of lung cancer. The relative risk of lung cancer for the lowest compared with the highest tertile of margarine intake was 4.0 (p less than 0.001), and that for fruits was 1.8 (p = 0.01). These associations persisted after adjustment for the micronutrient intakes and were stronger among nonsmokers. The results suggest that carotenoids, vitamin E, and vitamin C may be protective against lung cancer among nonsmokers. Food sources rich in these micronutrients may also have other constituents with independent protective effects against lung cancer.

The relation between dietary cholesterol and fatty acids and the incidence of lung cancer was studied among 4,538 Finnish men aged 20-69 years and initially free of cancer. During 20 years of follow-up, 117 lung cancer cases were diagnosed. Cholesterol intake was not associated with lung cancer risk, the age-, smoking-, and energy-adjusted relative risk between the lowest and highest tertiles being 1.0 [95% confidence interval (CI) = 0.6-1.9]. The intake of saturated fatty acids was nonsignificantly related with lung cancer incidence, the relative risk for the lowest compared with the highest tertile being 1.6 (CI = 0.8-3.2). The association was stronger among smokers than among nonsmokers, the relative risks being 2.1 (CI = 1.0-4.3) and 1.3 (CI = 0.4-4.1), respectively. The relative risk among smokers, however, decreased to 1.5 after adjustment for the amount they smoked. In the total cohort, there was a significantly elevated risk of lung cancer among men with a high intake of butter, one of the main sources of saturated fatty acids, the relative risk being 1.9 (CI = 1.1-3.2). The present data do not confirm previous results suggesting that dietary cholesterol predicts the occurrence of lung cancer among men. The association between intake of saturated fatty acids and lung cancer observed in the present study may be partly due to heavy smoking among high consumers of saturated fat.

Respiratory cancer was examined in relation to occupational formaldehyde exposure in a case-referent study (136 cases, 408 referents) nested in a woodworker cohort. Plant- and time-specific job-exposure matrices were constructed for formaldehyde exposure. Over 3 ppm-months of formaldehyde exposure was associated with an odds ratio of 1.4 [90% confidence interval (90% CI) 0.5-4.1]. The odds ratios for lung cancer were near unity, the excess risk concentrating on the upper respiratory tract. That for combined exposure to formaldehyde-phenol exposure (all respiratory cancers) was 1.6 (90% CI 0.6-4.4) but 1.0 for formaldehyde only. No consistent exposure-response patterns emerged for the level, duration, or cumulative exposure. The results are hardly more than debatable support for the hypothesis concerning formaldehyde as a carcinogen in humans, the possible risk seemingly concentrating on the upper respiratory tract rather than the lung.

A total of 3749 workers employed for at least three months in two Finnish glass factories (cohorts A and B) were followed up for cancer in 1953-86 through the Finnish Cancer Registry. In cohort A (1353 men, 1261 women), 106 primary cancers were diagnosed among men, and their standardised incidence ratio (SIR) for all cancers was 99. Among women the risk was low (65 cases, SIR 64). In cohort B (450 men, 685 women), the relative risk of cancer was close to unity for both men (57 cases) and women (75 cases). The risk of cancer was analysed by primary site, type of work, years since first exposure, and age at diagnosis. The only significantly increased risks were those of lung cancer among men (SIR 130, 95% CI 100-167, cohorts A and B combined), and skin cancer among glass blowers (SIR 625, 95% CI 129-1827). An increased risk of lung, stomach, and colon cancer as well as of brain tumours has been reported in previous studies. It is postulated that the excess risk of lung cancer, detected in this study, can also be accounted for by lifestyle, and not only by possible occupational exposures, because a similar excess risk of lung cancer has been found previously for all industrial workers in Finland. Although the risk of stomach cancer in this study was increased among glass blowers, it was not high in the largest groups of plain glass workers. The risks of tumours of the central nervous system and colon were not increased either.

A case-referent study was undertaken to investigate the associations between formaldehyde exposure and respiratory and related cancers. Fifty-seven such cancers from a retrospective cohort of male woodworkers formed the case group. They were matched by year of birth with 171 referents. Exposure to formaldehyde was assessed with job-exposure matrices. The median of the time-weighted average concentration was about 1 ppm, and the mean duration of exposure was 10 years among the exposed. Odds ratios (OR) were calculated for formaldehyde exposure (1.44), peak exposure to formaldehyde (1.26), and exposure to formaldehyde-containing wood dust (1.22). None of the values exceeded unity with statistical significance. Allowance was also made for a 10-year period from the onset of exposure. Birth year, cigarette smoking and exposure to wood dust, chlorophenols, pesticides, and terpenes were controlled by stratification. The adjusted ORs did not change appreciably. The highest OR was 1.95 for formaldehyde exposure without allowance for minimum latency, adjusted for exposure to terpenes. No exposure-response relation was observed for the level, duration, or dose (ppm-years) of formaldehyde exposure. The result is nonpositive and may be explained by absence of effect, by too short a follow-up, or by insufficient power for detecting a mild excess risk.

The standardized incidence ratio (SIR) of lung cancer was determined for different occupational groups in Finland. The data on all cases of lung cancer diagnosed in Finland in age groups of 35-69 years in 1971-1975 were supplemented by information on occupation from the 1970 census (Central Statistical Office). The expected numbers of cases were based on the sex, age and occupation-specific numbers of person-years computed in the Central Statistical Office, and sex- and age-specific incidence rates of lung cancer among the economically active population (as defined 1 January 1971). Compared with the risk of the total economically active population, the relative risk of those not active (SIR) was 1.69 for men and 0.86 for women. Lower than expected relative risks were encountered among highly educated and white-collar male workers (religious, legal, pedagogical, medical, technical and administrative work), in sales work, transport service work and among farmers. High SIRs were found in mining and quarrying, forestry, woodworking (joiners), construction, painting and among unskilled workers. Among women the numbers of cases were small and only one significant SIR was obtained; the risk was lower than expected in farming. Data on the smoking habits of males in different main occupational categories in Finland show that variation between different occupational groups in the prevalence of smoking closely corresponds to that in the SIR for lung cancer (R = 0.96).