Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Occupational exposure to nickel and hexavalent chromium and the risk of lung cancer in a pooled analysis of case-control studies (SYNERGY).

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.

Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain).

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (

Exposure to pesticides and risk of Hodgkin lymphoma in an international consortium of agricultural cohorts (AGRICOH).

PURPOSE: Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined associations between agricultural use of 22 individual active ingredients and 13 chemical groups and HL incidence. METHODS: We used data from three agricultural cohorts participating in the AGRICOH consortium: the French Agriculture and Cancer Cohort (2005-2009), Cancer in the Norwegian Agricultural Population (1993-2011), and the US Agricultural Health Study (1993-2011). Lifetime pesticide use was estimated from crop-exposure matrices or self-report. Cohort-specific covariate-adjusted overall and age-specific (< 40 or ≥ 40 years) hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression and combined using random effects meta-analysis. RESULTS: Among 316 270 farmers (75% male) accumulating 3 574 815 person-years at risk, 91 incident cases of HL occurred. We did not observe statistically significant associations for any of the active ingredients or chemical groups studied. The highest risks of HL overall were observed for the pyrethroids deltamethrin (meta-HR = 1.86, 95% CI 0.76-4.52) and esfenvalerate (1.86, 0.78-4.43), and inverse associations of similar magnitude were observed for parathion and glyphosate. Risk of HL at ≥ 40 years of age was highest for ever-use of dicamba (2.04, 0.93-4.50) and lowest for glyphosate (0.46, 0.20-1.07). CONCLUSION: We report the largest prospective investigation of these associations. Nonetheless, low statistical power, a mixture of histological subtypes and a lack of information on tumour EBV status complicate the interpretability of the results. Most HL cases occurred at older ages, thus we could not explore associations with adolescent or young adult HL. Furthermore, estimates may be attenuated due to non-differential exposure misclassification. Future work should aim to extend follow-up and refine both exposure and outcome classification.

Changes in Population Health-Related Behaviors During a COVID-19 Surge: A Natural Experiment.

BACKGROUND: The study of impact of lockdowns on individual health-related behaviors has produced divergent results. PURPOSE: To identify patterns of change in multiple health-related behaviors analyzed as a whole, and their individual determinants. METHODS: Between March and August 2020, we collected data on smoking, alcohol, physical activity, weight, and sleep in a population-based cohort from Catalonia who had available pre-pandemic data. We performed multiple correspondence and cluster analyses to identify patterns of change in health-related behaviors and built multivariable multinomial logistic regressions to identify determinants of behavioral change. RESULTS: In 10,032 participants (59% female, mean (SD) age 55 (8) years), 8,606 individuals (86%) modified their behavior during the lockdown. We identified five patterns of behavioral change that were heterogeneous and directed both towards worsening and improvement in diverse combinations. Patterns ranged from "global worsening" (2,063 participants, 21%) characterized by increases in smoking, alcohol consumption, and weight, and decreases in physical activity levels and sleep time, to "improvement" (2,548 participants, 25%) characterized by increases in physical activity levels, decreases in weight and alcohol consumption, and both increases and decreases in sleep time. Being female, of older age, teleworking, having a higher education level, assuming caregiving responsibilities, and being more exposed to pandemic news were associated with changing behavior (all p < .05), but did not discriminate between favorable or unfavorable changes. CONCLUSIONS: Most of the population experienced changes in health-related behavior during lockdowns. Determinants of behavior modification were not explicitly associated with the direction of changes but allowed the identification of older, teleworking, and highly educated women who assumed caregiving responsibilities at home as susceptible population groups more vulnerable to lockdowns.

Lockdowns implemented during the first surge of the COVID-19 pandemic created highly disruptive scenarios impacting many aspects of life, including health-related behaviors. While early studies on isolated health-related behaviors partly aid in the understanding of changes in some of these behaviors, there is robust evidence supporting the idea that health-related behaviors and their changes often co-occur and should be studied and analyzed as a whole. Hence, in this study, we used hypothesis-free methods to identify inter-dependent patterns of change in health-related behaviors including tobacco smoking, alcohol consumption, physical activity, sleep, and weight in a population-based sample of 10,032 adults from Catalonia, Spain. We found that 86% of participants modified their health-related behavior during the lockdown as we identified five patterns of behavioral change, ranging from general worsening to improvement, in diverse combinations. Additionally, we found that being female, older age, teleworking, highly educated, assuming caregiving responsibilities, and having a high exposure to pandemic news were main the determinants of patterns characterized by changing behaviors (both worsening and improving). Overall, our results highlight the heterogeneity, co-occurrence, and inter-play between health-related behaviors under a natural experiment, and identify common demographic, socio-environmental and behavioral factors that might predict changes in behavior.

Lung cancer mortality in the European cohort of titanium dioxide workers: a reanalysis of the exposure-response relationship.

OBJECTIVES: Animal bioassays have demonstrated convincing evidence of the potential carcinogenicity to humans of titanium dioxide (TiO2), but limitations in cohort studies have been identified, among which is the healthy worker survivor effect (HWSE). We aimed to address this bias in a pooled study of four cohorts of TiO2 workers. METHODS: We reanalysed data on respirable TiO2 dust exposure and lung cancer mortality among 7341 male workers employed in TiO2 production in Finland, France, UK and Italy using the parametric g-formula, considering three hypothetical interventions: setting annual exposures at 2.4 (U.S. occupational exposure limit), 0.3 (German limit) and 0 mg/m3 for 25 and 35 years. RESULTS: The HWSE was evidenced. Taking this into account, we observed a positive association between lagged cumulative exposure to TiO2 and lung cancer mortality. The estimated number of lung cancer deaths at each age group decreased across increasingly stringent intervention levels. At age 70 years, the estimated number of lung cancer deaths expected in the cohort after 35-year exposure was 293 for exposure set at 2.4 mg/m3, 235 for exposure set at 0.3 mg/m3, and 211 for exposure set at 0 mg/m3. CONCLUSION: This analysis shows that HWSE can hide an exposure-response relationship. It also shows that TiO2 epidemiological data could demonstrate an exposure-effects relationship if analysed appropriately. More epidemiological studies and similar reanalyses of existing cohort studies are warranted to corroborate the human carcinogenicity of TiO2. This human evidence, when combined with the animal evidence, strengthens the overall evidence of carcinogenicity of TiO2.

Conducting evaluations of evidence that are transparent, timely and can lead to health-protective actions.

BACKGROUND: In February 2021, over one hundred scientists and policy experts participated in a web-based Workshop to discuss the ways that divergent evaluations of evidence and scientific uncertainties are used to delay timely protection of human health and the environment from exposures to hazardous agents. The Workshop arose from a previous workshop organized by the European Environment Agency (EEA) in 2008 and which also drew on case studies from the EEA reports on 'Late Lessons from Early Warnings' (2001, 2013). These reports documented dozens of hazardous agents including many chemicals, for which risk reduction measures were delayed for decades after scientists and others had issued early and later warnings about the harm likely to be caused by those agents. RESULTS: Workshop participants used recent case studies including Perfluorooctanoic acid (PFOA), Extremely Low Frequency - Electrical Magnetic Fields (ELF-EMF fields), glyphosate, and Bisphenol A (BPA) to explore myriad reasons for divergent outcomes of evaluations, which has led to delayed and inadequate protection of the public's health. Strategies to overcome these barriers must, therefore, at a minimum include approaches that 1) Make better use of existing data and information, 2) Ensure timeliness, 3) Increase transparency, consistency and minimize bias in evidence evaluations, and 4) Minimize the influence of financial conflicts of interest. CONCLUSION: The recommendations should enhance the production of "actionable evidence," that is, reliable evaluations of the scientific evidence to support timely actions to protect health and environments from exposures to hazardous agents. The recommendations are applicable to policy and regulatory settings at the local, state, federal and international levels.

Secondhand smoke exposure and oral cancer risk: a systematic review and meta-analysis.

OBJECTIVES: Inhalation of secondhand smoke (SHS) causes several diseases, including lung cancer. Tobacco smoking is a known cause of oral cancer; however, it has not been established whether SHS also causes oral cancer . The aim of this study was to evaluate the potential association between SHS exposure and the risk of oral cancer. METHODS: A systematic review and meta-analysis study (following the PRISMA guidelines) was developed to examine the studies reporting on the associations of SHS and the risk of oral cancer, employing a search strategy on electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, Open Grey, and ProQuest databases for dissertations) until 10 May 2020. Meta-analyses and sensitivity analyses were performed using random-effect models. The protocol was registered in PROSPERO (CRD42020189970). RESULTS: Following the application of eligibility criteria, five studies were included, comprising a total of 1179 cases and 5798 controls, with 3452 individuals exposed and 3525 individuals not exposed to SHS. An overall OR of 1.51 (95% CI 1.2o to 1.91, p=0.0004) for oral cancer was observed, without significant heterogeneity (I2=0%, p=0.41). The duration of exposure of more than 10 or 15 years increased the risk of oral cancer (OR 2.07, 95% CI 1.54 to 2.79, p<0.00001), compared with non-exposed individuals, without significant heterogeneity (I2=0%, p=0.76). CONCLUSIONS: This systematic review and meta-analysis supports a causal association between SHS exposure and oral cancer. Our results could provide guidance to public health professionals, researchers, and policymakers to further support effective SHS exposure prevention programs worldwide.

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

Aspartame and cancer - new evidence for causation.

BACKGROUND: Aspartame is one of the world's most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI's diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. METHODS: To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. FINDINGS: This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. INTERPRETATION: These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame's health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame's carcinogenicity to humans.

Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case-Control Studies.

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

Parental occupational exposure to pesticides, animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C).

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case-control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97-10.68; insecticides HR = 2.86, 95% CI = 0.99-8.23; animals HR = 3.89, 95% CI = 1.18-12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12-5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31-0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.

Occupational Noise Exposure and Vestibular Schwannoma: A Case-Control Study in Sweden.

It has been suggested that the association between self-reported occupational noise exposure and vestibular schwannoma (VS), found in several studies, represents recall bias. Therefore, we aimed to study the relationship in a large case-control study using occupational noise measurements. We performed a case-control study using data from Sweden for 1,913 VS cases diagnosed in 1961-2009 and 9,566 age- and sex-matched population controls. We defined occupational history by linkage to national censuses from 1960, 1970, 1980, and 1990. We estimated occupational noise exposure for each case and control using a job-exposure matrix. There was no association between occupational noise exposure and VS. Among subjects assessed as ever exposed to occupational noise levels of ≥85 dB (214 cases and 1,142 controls), the odds ratio for VS per 5 years of exposure was 1.02 (95% confidence interval: 0.90, 1.17). Workers with noise levels of ≥85 dB for at least 15 years (5-year latency period), showed no increased risk of VS (odds ratio = 0.98, 95% confidence interval: 0.73, 1.31) compared with those who had never been exposed to noise levels of 75 dB or higher. In summary, our large study does not support an association between occupational noise exposure and VS.

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.

Lung cancer mortality in the French cohort of titanium dioxide workers: some aetiological insights.

OBJECTIVES: Titanium dioxide (TiO2) is widely used in construction, food, cosmetic and medical industry. The current evidence on TiO2 carcinogenicity in humans is considered inadequate. As French participants of the European cohort of TiO2 workers exhibited an increase in mortality from lung cancer, we aimed at investigating whether TiO2 exposure, co-exposures or smoking can explain this increase. METHODS: We reanalysed the data of 833 French male workers (follow-up period 1968-1997) and used multiple imputation to complete their smoking status. We considered respirable TiO2 dust as primary exposure of interest, estimated as continuous cumulative (mg/m3-year) and annual average (mg/m3) concentrations and binary and 4-class categorical variables, with cut-off values of 0.3 and 2.4 mg/m3 (the German and American occupational exposure limits, respectively). For each exposure metric, we estimated HRs and associated 95% CIs, using Cox regression models adjusted for calendar period, exposure duration and smoking. RESULTS: The fully adjusted model yielded a HR=3.7 (95% CI=0.79 to 17.95) for TiO2-exposed workers vs unexposed and a HR=27.33 (95% CI=4.35 to 171.84) for those exposed to >2.4 mg/m3 as annual average concentration. Employment duration was negatively related with lung cancer mortality, therefore cumulative exposure had a small effect on mortality (HR=1.03 (95% CI=0.99 to 1.08) per mg/m3-year). CONCLUSION: This study suggests a positive relationship between TiO2 exposure and lung cancer mortality in TiO2 workers, whatever the exposure variable used, despite a limited statistical power in some models. The results question the current evidence on TiO2 carcinogenicity in humans but need to be confirmed in other cohorts, using different statistical approaches.

Smokeless tobacco control in 180 countries across the globe: call to action for full implementation of WHO FCTC measures.

Smokeless tobacco is consumed by 356 million people globally and is a leading cause of head and neck cancers. However, global efforts to control smokeless tobacco use trail behind the progress made in curbing cigarette consumption. In this Policy Review, we describe the extent of the policy implementation gap in smokeless tobacco control, discuss key reasons on why it exists, and make recommendations on how to bridge this gap. Although 180 countries have agreed that the WHO Framework Convention on Tobacco Control is the best approach to control the demand and supply of smokeless tobacco, only 138 (77%) Parties define smokeless tobacco in their statutes. Only 34 (19%) Parties tax or report taxing smokeless tobacco products, six (3%) measure content and emissions of smokeless tobacco products, and 41 (23%) mandate pictorial health warnings on these products. Although awareness of the harms related to smokeless tobacco is growing in many parts of the world, few Parties collect or present data on smokeless tobacco use under global or national surveillance mechanisms (eg, Global Tobacco Surveillance System and WHO STEPwise). Only 16 (9%) Parties have implemented a comprehensive ban on smokeless tobacco advertisement, promotion, and sponsorships. Globally, a smaller proportion of smokeless tobacco users are advised to quit the use of smokeless tobacco products compared to tobacco users. Use of smokeless tobacco is becoming a global cause of concern, requiring a greater commitment on the full implementation of the WHO Framework Convention on Tobacco Control measures.

Cancer incidence among workers with blood lead measurements in two countries.

OBJECTIVE: Study carcinogenicity of inorganic lead, classified as 'probably carcinogenic' to humans by the International Agency for Research on Cancer (brain, lung, kidney and stomach). METHODS: We conducted internal and external analyses for cancer incidence in two cohorts of 29 874 lead-exposed workers with past blood lead data (Finland, n=20 752, Great Britain=9122), with 6790 incident cancers. Exposure was maximum measured blood lead. RESULTS: The combined cohort had a median maximum blood lead of 29 µg/dL, a mean first blood lead test of 1977, and was 87% male. Significant (p<0.05) positive trends, using the log of maximum blood lead, were found for brain cancer (malignant), Hodgkin's lymphoma, lung cancer and rectal cancer, while a significant negative trend was found for melanoma. Borderline significant positive trends (0.05≤p≤0.10) were found for oesophageal cancer, meningioma and combined malignant/benign brain cancer. Categorical analyses reflected these trends. Significant interactions by country were found for lung, brain and oesophageal cancer, with Finland showing strong positive trends, and Great Britain showing modest or no trends. Larynx cancer in Finland also showed a positive trend (p=0.05). External analyses for high exposure workers (maximum blood lead >40 µg/dL) showed a significant excess for lung cancer in both countries combined, and significant excesses in Finland for brain and lung cancer. The Great Britain data were limited by small numbers for some cancers, and limited variation in exposure. CONCLUSIONS: We found strong positive incidence trends with increasing blood lead level, for several outcomes in internal analysis. Two of these, lung and brain cancer, were sites of a priori interest.