Risk of lung cancer among women in relation to lifetime history of tobacco smoking: a population-based case-control study in France (the WELCA study).

BACKGROUND: This study aims to provide new insights on the role of smoking patterns and cigarette dependence in female lung cancer, and to examine differences by histological subtype. METHODS: We conducted a population-based case-control study in the great Paris area among women including 716 incident cases diagnosed between 2014 and 2017 and 757 age-matched controls. Detailed data on smoking history was collected during in-person interviews to assess intensity and duration of tobacco smoking, time since cessation, smoking habits (depth of smoke inhalation, use of filter, type of tobacco, and type of cigarettes) and Fagerström test for cigarette dependence. The comprehensive smoking index (CSI), a score modelling the combined effects of intensity, duration and time since quitting smoking was determined for each subject. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and their confidence intervals (95%CI) of lung cancer associated with smoking variables. RESULTS: Lung cancer risk increased linearly with intensity and duration of tobacco smoking while it decreased with time since cessation, to reach the risk in never-smokers after 20 years of abstinence. The combined effect of intensity and duration of tobacco smoking was more than multiplicative (p-interaction 0.012). The OR in the highest vs the lowest quartile of CSI was 12.64 (95%CI 8.50; 18.80) (p-trend < 0.001). The risk of small cell or squamous cell carcinomas increased with the CSI more sharply than the risk of adenocarcinomas. Deep smoke inhalation, dark vs blond tobacco, conventional vs light cigarettes, and unfiltered vs filtered cigarettes, as well as having mixed smoking habits, were found to be independent risk factors. Having high cigarette addiction behaviours also increased the risk after adjusting for CSI. CONCLUSION: This study provides additional insights on the effects of tobacco smoking patterns on lung cancer risk among women.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

Welding and the risk of head and neck cancer: the ICARE study.

OBJECTIVE: To investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study. METHODS: Analyses were restricted to men (2703 controls and 1588 cases of squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx). Welding activity and potential confounders were assessed by detailed questionnaires. ORs and CIs (95% CI) were estimated by unconditional logistic regression, adjusted for age, area of residence, tobacco smoking, alcohol consumption and occupational exposure to asbestos. RESULTS: Welding was associated with an increased risk of head and neck cancer overall (OR=1.31, 95% CI 1.03 to 1.67). The association was strongest for laryngeal cancer (OR=1.66, 95% CI 1.15 to 2.38) and the risk increased with the cumulative duration (p-trend <0.01) and the weighted duration (p-trend <0.01) of welding. A cumulative duration and a weighted duration of welding of more than 10 years were also associated with a significantly increased risk of oral cancer (OR=1.82, 95% CI 1.09 to 3.04; OR=2.10, 95% CI 0.99 to 4.45, respectively). A long duration of arc welding was associated with laryngeal cancer, whereas a long duration of spot welding was associated with oral cancer. Welding was not associated with the risk of oropharyngeal and hypopharyngeal cancer. CONCLUSION: Our findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.

Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system - Results from three French case-control studies.

OBJECTIVES: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults. METHODS: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2029 lung cancer cases and 2591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure. RESULTS: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR = 1.51; 95% CI: 1.22-1.86 and brain tumors (OR = 1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR = 0.78; 95% CI: 0.46-1.33). CONCLUSION: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.

Diagnostic and Prognostic Performance of Blood Plasma Glycan Features in the Women Epidemiology Lung Cancer (WELCA) Study.

Lung cancer is the leading cause of cancer death in women living in the United States, which accounts for approximately the same percentage of cancer deaths in women as breast, ovary, and uterine cancers combined. Targeted blood plasma glycomics represents a promising source of noninvasive diagnostic and prognostic biomarkers for lung cancer. Here, 208 samples from lung cancer patients and 207 age-matched controls enrolled in the Women Epidemiology Lung Cancer (WELCA) study were analyzed by a bottom-up glycan "node" analysis approach. Glycan features, quantified as single analytical signals, including 2-linked mannose, α2-6 sialylation, ß1-4 branching, ß1-6 branching, 4-linked GlcNAc, and antennary fucosylation, exhibited abilities to distinguish cases from controls (ROC AUCs: 0.68-0.92) and predict survival in patients (hazard ratios: 1.99-2.75) at all stages. Notable alterations of glycan features were observed in stages I-II. Diagnostic and prognostic glycan features were mostly independent of smoking status, age, gender, and histological subtypes of lung cancer.

Occupational exposure to wood dust and risk of lung cancer: the ICARE study.

OBJECTIVES: In a previous analysis of data from a French population-based case-control study (the Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE) study), 'having ever worked' in wood-related occupations was associated with excess lung cancer risk after adjusting for smoking but not for occupational factors. The present study aimed to investigate the relationship between lung cancer risk and wood dust exposure after adjusting for occupational exposures. METHODS: Data were obtained from 2276 cases and 2780 controls on smoking habits and lifelong occupational history, using a standardised questionnaire with a job-specific questionnaire for wood dust exposure. Logistic regression models were used to calculate ORs and 95% CIs adjusted for age, area of residence, tobacco smoking, the number of job periods and exposure to silica, asbestos and diesel motor exhaust (DME). RESULTS: No significant association was found between lung cancer and wood dust exposure after adjustment for smoking, asbestos, silica and DME exposures. The risk of lung cancer was slightly increased among those who were exposed to wood dust more than 10 years, and had over 40 years since the first exposure. CONCLUSION: Our findings do not provide a strong support to the hypothesis that wood dust exposure is a risk factor for lung cancer. This study showed the importance of taking into account smoking and occupational coexposures in studies on lung cancer and wood dust exposure. Further studies evaluating the level and frequency of exposure during various tasks in woodwork are needed.

Head and neck cancer and occupational exposure to leather dust: results from the ICARE study, a French case-control study.

BACKGROUND: Leather dust is an established carcinogen of the sinonasal cavities; however, evidence is lacking regarding its association with other head and neck cancers (HNC). To date, few studies have been conducted on the association between occupational leather dust exposure and the risk of oral, pharyngeal, and laryngeal cancers. The objective of this study was to investigate the association between the risk of HNC and occupational exposure to leather dust. METHODS: Lifestyle habits and occupational history were collected for 2161 patients with squamous cell carcinoma of oral cavity, pharynx, and larynx, and 3555 controls, using a standardized questionnaire. Occupational exposure to leather dust was assessed using a job-exposure matrix. Odds ratios (OR) and 95% confidence intervals (CI) for HNC globally and by subsite were estimated using multivariate unconditional, and polytomous logistic regressions, respectively. RESULTS: Cumulative lifetime exposure to leather dust < 6 mg/m3-years was associated with an increased risk of laryngeal cancer (OR = 2.26, 95% CI: 1.07-4.76); higher levels were not related to elevated risks of HNC. Some tasks performed and the use of some glues were associated with elevated, although non-significant, risks of HNC. No dose-response relationships were observed. CONCLUSION: Our study did not provide enough evidence for an increased risk of HNC related to occupational exposure to leather dust. Further studies are needed to understand the risks of specific tasks in the leather industry.

Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France: the ICARE study.

BACKGROUND: To examine associations between occupational exposure to petroleum-based and oxygenated solvents and the risk of hypopharyngeal and laryngeal cancer. METHODS: ICARE is a large, frequency-matched population-based case-control study conducted in France. Lifetime occupational history, tobacco smoking and alcohol consumption were collected. Analyses were restricted to men and included 383 cases of hypopharyngeal cancer, 454 cases of laryngeal cancer, and 2780 controls. Job-exposure matrices were used to assess exposure to five petroleum-based solvents (benzene; gasoline; white spirits; diesel, fuels and kerosene; special petroleum products) and to five oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). Odds ratios (ORs) adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals (CI) were estimated with unconditional logistic models. RESULTS: No significant association was found between hypopharyngeal or laryngeal cancer risk and exposure to the solvents under study. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of white spirits (OR = 1.46; 95% CI: 0.88-2.43) and tetrahydrofuran (OR = 2.63; 95CI%: 0.55-12.65), with some indication of a dose-response relationship (p for trend: 0.09 and 0.07 respectively). CONCLUSION: This study provides weak evidence for an association between hypopharyngeal cancer and exposure to white spirits and tetrahydrofuran, and overall does not suggest a substantial role of exposure to petroleum-based or oxygenated solvents in hypopharyngeal or laryngeal cancer risk.

Body mass index and lung cancer risk: a pooled analysis based on nested case-control studies from four cohort studies.

BACKGROUND: Obesity has been proposed as a potential protective factor against lung cancer. We examined the association between BMI and lung cancer risk in a pooled analysis based on nested case-control studies from four cohort studies. METHODS: A case-control study was nested within four cohorts in USA, Europe, China and Singapore that included 4172 cases and 8471 control subjects. BMI at baseline was calculated as weight in kilograms divided by height in meters squared (kg/m2), and classified into 4 categories: underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (≥30). Odds ratios (ORs) and 95% confidence intervals (CIs) for BMI-lung cancer associations were estimated using unconditional logistic regression, adjusting for potential confounders. RESULTS: Considering all participants, and using normal weight as the reference group, a decreased risk of lung cancer was observed for those who were overweight (OR 0.77, 95% CI: 0.68-0.86) and obese (OR 0.69, 95% CI: 0.59-0.82). In the stratified analysis by smoking status, the decreased risk for lung cancer was observed among current, former and never smokers (P for interaction 0.002). The adjusted ORs for overweight and obese groups were 0.79 (95% CI: 0.68-0.92) and 0.75 (95% CI: 0.60-0.93) for current smokers, 0.70 (95% CI: 0.53-0.93) and 0.55 (95% CI: 0.37-0.80) for former smokers, 0.77 (95% CI: 0.59-0.99), and 0.71 (95% CI: 0.44-1.14) for never smokers, respectively. While no statistically significant association was observed for underweight subjects who were current smokers (OR 1.24, 95% CI: 0.98-1.58), former smokers (OR 0.27, 95% CI: 0.12-0.61) and never smokers (OR 0.83, 95% CI: 0.5.-1.28). CONCLUSION: The results of this study provide additional evidence that obesity is associated with a decreased risk of lung cancer. Further biological studies are needed to address this association.

Time-dependent effect of intensity of smoking and of occupational exposure to asbestos on the risk of lung cancer: results from the ICARE case-control study.

OBJECTIVE: To estimate the impact of intensity of both smoking and occupational exposure to asbestos on the risk of lung cancer throughout the whole exposure history. METHODS: Data on 2026 male cases and 2610 male controls came from the French ICARE (Investigation of occupational and environmental causes of respiratory cancers) population-based, case-control study. Lifetime smoking history and occupational history were collected from standardised questionnaires and face-to-face interviews. Occupational exposure to asbestos was assessed using a job exposure matrix. The effects of annual average daily intensity of smoking (reported average number of cigarettes smoked per day) and asbestos exposure (estimated average daily air concentration of asbestos fibres at work) were estimated using a flexible weighted cumulative index of exposure in logistic regression models. RESULTS: Intensity of smoking in the 10 years preceding diagnosis had a much stronger association with the risk of lung cancer than more distant intensity. By contrast, intensity of asbestos exposure that occurred more than 40 years before diagnosis had a stronger association with the risk of lung cancer than more recent intensity, even if intensity in the 10 years preceding diagnosis also had a significant effect. CONCLUSION: Our results illustrate the dynamic of the effect of intensity of both smoking and occupational exposure to asbestos on the risk of lung cancer. They confirm that the timing of exposure plays an important role, and suggest that standard analytical methods assuming equal weights of intensity over the whole exposure history may be questionable.

Occupational exposure to flour dust and the risk of head and neck cancer.

BACKGROUND: To investigate the association between head and neck squamous cell cancer (HNSCC) risk and occupational exposure to flour dust in women and men, using data from ICARE, a French population-based case-control study. METHODS: The analysis included 2053 cases of HNSCC and 3507 controls. Lifelong occupational history was collected. A job-exposure matrix was used to assess exposure to flour dust. Odds-ratios (ORs) and 95% confidence intervals (CI), adjusted for smoking, alcohol drinking, and asbestos exposure, were estimated with logistic regression models. RESULTS: Ever exposure to flour dust was associated with elevated ORs in women (OR = 2.15, 95%CI: 1.01 4.55) and in men (OR = 1.55, 95%CI: 1.11 2.17). In women, the risk increased with the probability, the duration, and the cumulative level of exposure. No dose-response relationships were observed in men. CONCLUSIONS: Although the results were less conclusive in men than in women, overall, these findings provide some support to the hypothesis of a role of flour dust in the occurrence of HNSCC.

Occupational exposure to textile dust and lung cancer risk: Results from the ICARE Study.

BACKGROUND: To investigate the association of lung cancer with occupational exposure to textile dust and specifically to cotton dust in the population-based case-control study ICARE. METHODS: Lifelong occupational history of 2926 cases and 3555 controls was collected using standardized questionnaires, with specific questions for textile dust exposure. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models controlling for confounding factors including smoking and asbestos exposure. RESULTS: An inverse association between textile dust exposure and lung cancer was found among workers exposed ≥5% of their work time (OR = 0.80, 95%CI = 0.58-1.09), more pronounced for distant exposures (40+ years; up to a 56% reduced risk, statistically significant). The OR of lung cancer was significantly decreased among workers exposed to cotton fibers (OR = 0.70, 95%CI = 0.48-0.97). CONCLUSIONS: Our results provide some evidence of a decreased risk of lung cancer associated with exposure to textile dust, particularly cotton.

Prevalence of occupational exposure to asbestos and crystalline silica according to phenotypes of lung cancer from the CaProMat study: A case-only study.

BACKGROUND: The objective of the study was to compare the prevalence of occupational exposure to asbestos and crystalline silica according to histological types of lung cancer and age at diagnosis. METHODS: CaProMat study is a pooled case-only study conducted between 1996 and 2011. The current study consisted of 6521 lung cancer cases. Occupational exposure to asbestos and crystalline silica was assessed by two Job-Exposure Matrices. A weighted prevalence of exposure was derived and compared according to histological types and age at diagnosis. RESULTS: There was no difference of weighted prevalence of exposure to asbestos and crystalline silica according to histological types of lung cancer. There was a statistically significant difference of weighted prevalence of exposure to asbestos and crystalline silica according to age at diagnosis. CONCLUSIONS: Due to the limited clinical importance of the difference, neither the histological type, nor the age at diagnosis can be used as an indicator for the occupational exposure to asbestos or crystalline silica.

Menstrual and reproductive factors and lung cancer risk: A pooled analysis from the international lung cancer consortium.

Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in nonreproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression. Subgroup analyses were done for menopause status, smoking habits and histology. We found no strong support for an association of age at menarche and at menopause with lung cancer, but peri/postmenopausal women were at higher risk compared to premenopausal (OR 1.47, 95% CI 1.11-1.93). Premenopausal women showed increased risks associated with parity (OR 1.74, 95% CI 1.03-2.93) and number of children (OR 2.88, 95% CI 1.21-6.93 for more than 3 children; p for trend 0.01) and decreased with breastfeeding (OR 0.54, 95% CI 0.30-0.98). In contrast, peri/postmenopausal subjects had ORs around unity for the same exposures. No major effect modification was exerted by smoking status or cancer histology. Menstrual and reproductive factors may play a role in the genesis of lung cancer, yet the mechanisms are unclear, and smoking remains the most important modifiable risk factor. More investigations in large well-designed studies are needed to confirm these findings and to clarify the underlying mechanisms of gender differences in lung cancer risk.

Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study.

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies.

BACKGROUND: Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies. METHODS: We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends. RESULTS: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women. CONCLUSIONS: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.).

Occupational exposure to endotoxins and lung cancer risk: results of the ICARE Study.

OBJECTIVES: To investigate the role of occupational exposure to endotoxins in lung cancer in a French population-based case-control study (ICARE (Investigation of occupational and environmental causes of respiratory cancers)). METHODS: Detailed information was collected on the occupational history and smoking habits from 2926 patients with histologically confirmed lung cancer and 3555 matched controls. We evaluated each subject's endotoxin exposure after cross referencing International Standard Classification of Occupations (ISCO) codes (for job tasks) and Nomenclature d'Activités Françaises (NAF) codes (for activity sectors). Endotoxin exposure levels were attributed to each work environment based on literature reports. ORs and 95% CIs were estimated using unconditional logistic regression models and controlled for main confounding factors. RESULTS: An inverse association between exposure to endotoxins and lung cancer was found (OR=0.80, 95% CI 0.66 to 0.95). Negative trends were shown with duration and cumulative exposure, and the risk was decreased decades after exposure cessation (all statistically significant). Lung cancer risk was particularly reduced among workers highly exposed (eg, in dairy, cattle, poultry, pig farms), but also in those weakly exposed (eg, in waste treatment). Statistically significant interactions were shown with smoking, and never/light smokers were more sensitive to an endotoxin effect than heavy smokers (eg, OR=0.14, 95% CI 0.06 to 0.32 and OR=0.80, 95% CI 0.45 to 1.40, respectively, for the quartiles with the highest cumulative exposure, compared with those never exposed). Pronounced inverse associations were shown with adenocarcinoma histological subtype (OR=0.37, 95% CI 0.25 to 0.55 in the highly exposed). CONCLUSIONS: Our findings suggest that exposure to endotoxins, even at a low level, reduces the risk of lung cancer.

Occupational exposure to chlorinated solvents and risk of head and neck cancer in men: a population-based case-control study in France.

BACKGROUND: Few epidemiological studies have investigated the link between occupational exposure to solvents and head and neck cancer risk, and available findings are sparse and inconsistent. The objective of this study was to examine the association between occupational exposure to chlorinated solvents and head and neck cancer risk. METHODS: We analyzed data from 4637 men (1857 cases and 2780 controls) included in a population-based case-control study, ICARE (France). Occupational exposure to five chlorinated solvents (perchloroethylene [PCE], trichloroethylene [TCE], methylene chloride [MC], chloroform [CF], and carbon tetrachloride [CT]) was assessed through job-exposure matrices. Odds ratios (ORs) and confidence intervals (95% CI) were estimated by unconditional logistic regression, adjusted for age, tobacco smoking, alcohol consumption, asbestos exposure, and other potential confounders. RESULTS: We observed no association between chlorinated solvent exposure and head and neck cancer risk, despite a non-significant increase in risk among subjects who had the highest cumulative level of exposure to PCE, (OR = 1.81; 95% CI = 0.68 to 4.82). In subsite analysis, the risk of laryngeal cancer increased with cumulative exposure to PCE (p for trend = 0.04). The OR was 3.86 (95% CI = 1.30 to 11.48) for those exposed to the highest levels of PCE. A non-significant elevated risk of hypopharyngeal cancer was also observed in subjects exposed to the highest levels of MC (OR = 2.36; 95% CI = 0.98 to 5.85). CONCLUSION: Our findings provide evidence that high exposure to PCE increases the risk of laryngeal cancer, and suggest an association between exposure to MC and hypopharyngeal cancer. Exposure to other chlorinated solvents was not associated with the risk of head and neck cancer.

Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions.

BACKGROUND: Tobacco smoking is the main cause of lung cancer, but it is not the sole causal factor. Significant proportions of workers are smokers and exposed to occupational lung carcinogens. This study aims to systematically review the statistical interaction between occupational lung carcinogens and tobacco smoking, in particular asbestos, crystalline silica and diesel engine exhaust emissions. METHODS: Articles were identified using Scopus, PubMed, and Web of Science, and were limited to those published in English or French, without limitation of time. The reference list of selected studies was reviewed to identify other relevant papers. One reviewer selected the articles based on the inclusion and exclusion criteria. Two reviewers checked the eligibility of articles to be included in the systematic review. Data were extracted by one reviewer and revised by two other reviewers. Cohorts and case-control studies were analyzed separately. The risk of bias was evaluated for each study based on the outcome. The results of the interaction between the tobacco smoking and each carcinogen was evaluated and reported separately. RESULTS: Fifteen original studies were included for asbestos-smoking interaction, seven for silica-smoking interaction and two for diesel-smoking interaction. The results suggested the absence of multiplicative interaction between the three occupational lung carcinogens and smoking. There is no enough evidence from the literature to conclude for the additive interaction. We believe there is a limited risk of publication bias as several studies reporting negative results were published. CONCLUSION: There are no multiplicative interactions between tobacco smoking and occupational lung carcinogens, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Even though, specific programs should be developed and promoted to reduce concomitantly the exposure to occupational lung carcinogens and tobacco smoking.

Women Epidemiology Lung Cancer (WELCA) study: reproductive, hormonal, occupational risk factors and biobank.

BACKGROUND: Lung cancer aetiology and clinical aspects have been mainly studied in men, although specific risk factors probably exist in women. Here we present the rationale, design and organization of the WELCA study (Women Epidemiology Lung CAncer) that has been launched to investigate lung cancer in women, focusing particularly on hormonal and occupational factors. METHODS/DESIGN: WELCA is a population based case-control study and planned to recruit 1000 cases and 1000 controls in three years, based on study power calculation. Eligible cases are female patients newly diagnosed with lung cancer, living in Paris and the Ile de France area and aged up to 75 years. Almost all Parisian pneumology and oncology clinical departments are involved. The control group is a random sample of the population living in the same area, frequency-matched on age and additionally stratified on the distribution of socio-professional categories of women residing there. After acquisition of written consent, research nurses administer standardized computer assisted questionnaires to all the subjects in face-to-face interviews and acquire anthropometric measures. Besides usual socio-demographic characteristics, information is gathered about menstrual and reproductive factors, hormonal treatments, lifestyle and leisure characteristics, occupational history, personal and familial medical history. Biological samples are also collected, in order to establish a biobank for molecular epidemiology studies. Molecular characteristics of the tumours will be obtained and patients will be followed up for five years. DISCUSSION: The WELCA study aims to answer key questions in lung cancer aetiology and clinical characteristics specifically in women. The role of hormonal impregnation is investigated, and the interactions with cigarette smoking or body mass index (BMI) will be analyzed in detail. The occupational history of the subjects is carefully reconstructed, focusing in particular on the service sector. The creation of a biobank for collection of serum, plasma, DNA and tumour tissue will allow the genetic and biochemical characterization of both the subjets and the tumours. The follow-up of the patients will help in disentangling the role of hormonal factors and tumour molecular characteristics in survival.