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.

Systematic reviews as a 'lens of evidence': Determinants of benefits and harms of breast cancer screening.

This systematic review, stimulated by inconsistency in secondary evidence, reports the benefits and harms of breast cancer (BC) screening and their determinants according to systematic reviews. A systematic search, which identified 9,976 abstracts, led to the inclusion of 58 reviews. BC mortality reduction with screening mammography was 15-25% in trials and 28-56% in observational studies in all age groups, and the risk of stage III+ cancers was reduced for women older than 49 years. Overdiagnosis due to mammography was 1-60% in trials and 1-12% in studies with a low risk of bias, and cumulative false-positive rates were lower with biennial than annual screening (3-17% vs 0.01-41%). There is no consistency in the reviews' conclusions about the magnitude of BC mortality reduction among women younger than 50 years or older than 69 years, or determinants of benefits and harms of mammography, including the type of mammography (digital vs screen-film), the number of views and the screening interval. Similarly, there was no solid evidence on determinants of benefits and harms or BC mortality reduction with screening by ultrasonography or clinical breast examination (sensitivity ranges, 54-84% and 47-69%, respectively), and strong evidence of unfavourable benefit-to-harm ratio with breast self-examination. The reviews' conclusions were not dependent on the quality of the reviews or publication date. Systematic reviews on mammography screening, mainly from high-income countries, systematically disagree on the interpretation of the benefit-to-harm ratio. Future reviews are unlikely to clarify the discrepancies unless new original studies are published.

Cancer mortality in an international cohort of reinforced plastics workers exposed to styrene: a reanalysis.

OBJECTIVE: To investigate the carcinogenicity of styrene by reanalysing data from a previous international cohort study of workers in the reinforced plastics industry. METHODS: Mortality from cancers of prior interest was analysed with more detailed consideration of exposure-response relations and an updated classification of leukaemias and lymphomas in data from a previous international cohort study of 37 021 reinforced plastics workers exposed to airborne styrene. RESULTS: Increased mortality from non-Hodgkin's lymphoma (NHL) was associated with the mean level of exposure to styrene in air (relative risk (RR) 2.31, 95% CI 1.29 to 4.12 per 100 ppm), but not with cumulative styrene exposure. Similar associations with mean exposure were observed for the oesophagus (RR 2.44, 95% CI 1.11 to 5.36 per 100 ppm) and pancreas (RR 1.89, 95% CI 1.17 to 3.09). Oesophageal cancer mortality was also associated with cumulative styrene exposure lagged 20 years (RR 1.16, 95% CI 1.03 to 1.31). No other cancer, including lung cancer, was associated with any indicator of styrene exposure. CONCLUSION: This reanalysis does not substantially change the conclusions of the original study with respect to NHL or lung cancer but new evidence concerning cancers of the oesophagus and pancreas merits further investigation.

Welding fumes and lung cancer: a meta-analysis of case-control and cohort studies.

BACKGROUND: An estimated 110 million workers are exposed to welding fumes worldwide. Welding fumes are classified by the International Agency for Research on Cancer as carcinogenic to humans (group 1), based on sufficient evidence of lung cancer from epidemiological studies. OBJECTIVE: To conduct a meta-analysis of case-control and cohort studies on welding or exposure to welding fumes and risk of lung cancer, accounting for confounding by exposure to asbestos and tobacco smoking. METHODS: The literature was searched comprehensively in PubMed, reference lists of relevant publications and additional databases. Overlapping populations were removed. Meta-relative risks (mRRs) were calculated using random effects models. Publication bias was assessed using funnel plot, Eggers's test and Begg's test. RESULTS: Forty-five studies met the inclusion criteria (20 case-control, 25 cohort/nested case-control), which reduced to 37 when overlapping study populations were removed. For 'ever' compared with 'never' being a welder or exposed to welding fumes, mRRs and 95% CIs were 1.29 (1.20 to 1.39; I2=26.4%; 22 studies) for cohort studies, 1.87 (1.53 to 2.29; I2=44.1%; 15 studies) for case-control studies and 1.17 (1.04 to 1.38; I2=41.2%) for 8 case-control studies that adjusted for smoking and asbestos exposure. The mRRs were 1.32 (95% CI 1.20 to 1.45; I2=6.3%; 15 studies) among 'shipyard welders', 1.44 (95% CI 1.07 to 1.95; I2=35.8%; 3 studies) for 'mild steel welders' and 1.38 (95% CI 0.89 to 2.13; I2=68.1%; 5 studies) among 'stainless steel welders'. Increased risks persisted regardless of time period, geographic location, study design, occupational setting, exposure assessment method and histological subtype. CONCLUSIONS: These results support the conclusion that exposure to welding fumes increases the risk of lung cancer, regardless of the type of steel welded, the welding method (arc vs gas welding) and independent of exposure to asbestos or tobacco smoking.

Coffee Drinking and the Risk of Endometrial Cancer: An Updated Meta-Analysis of Observational Studies.

BACKGROUND: Several compounds contained in coffee have been found to suppress carcinogenesis in experimental studies. We conducted a dose-response meta-analysis to assess the impact of coffee consumption on the risk of endometrial cancer. MATERIALS AND METHODS: We searched MEDLINE and EMBASE databases for studies published up to August 2016. Using random effects models, we estimated summary relative risks (RR) for cohort studies and odds ratios (OR) for case-control studies with 95% confidence intervals (CI). Dose-response analyses were conducted by using generalized least square trend estimation. RESULTS: We identified 12 cohort studies and 8 case-control studies eligible for inclusion, contributing with 11,663 and 2,746 endometrial cancer cases, respectively. The summary RR for highest compared with lowest coffee intake was 0.74 (95% CI: 0.68-0.81; pheterogeneity = 0.09, I2 = 32%). The corresponding summary RR among cohort studies was 0.78 (95% CI: 0.71-0.85; pheterogeneity = 0.14, I2 = 31.9%) and 0.63 (95% CI: 0.53-0.76; pheterogeneity = 0.57, I2 = 0%) for case-control studies. One-cup increment per day was associated with 3% risk reduction (95% CI: 2-4%) in cohort studies and 12% (95% CI: 5-18%) in case-control studies. After pooling the results from 5 cohort studies, the association remained significant only in women with body mass index over 30 (RR = 0.71, 95% CI: 0.61-0.81). CONCLUSION: The results from our meta-analysis strengthen the evidence of a protective effect of coffee consumption on the risk of EC and further suggest that increased coffee intake might be particularly beneficial for women with obesity.

Identifying occupational carcinogens: an update from the IARC Monographs.

The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data.

Target Organ Metabolism, Toxicity, and Mechanisms of Trichloroethylene and Perchloroethylene: Key Similarities, Differences, and Data Gaps.

Trichloroethylene (TCE) and perchloroethylene or tetrachloroethylene (PCE) are high-production volume chemicals with numerous industrial applications. As a consequence of their widespread use, these chemicals are ubiquitous environmental contaminants to which the general population is commonly exposed. It is widely assumed that TCE and PCE are toxicologically similar; both are simple olefins with three (TCE) or four (PCE) chlorines. Nonetheless, despite decades of research on the adverse health effects of TCE or PCE, few studies have directly compared these two toxicants. Although the metabolic pathways are qualitatively similar, quantitative differences in the flux and yield of metabolites exist. Recent human health assessments have uncovered some overlap in target organs that are affected by exposure to TCE or PCE, and divergent species- and sex-specificity with regard to cancer and noncancer hazards. The objective of this minireview is to highlight key similarities, differences, and data gaps in target organ metabolism and mechanism of toxicity. The main anticipated outcome of this review is to encourage research to 1) directly compare the responses to TCE and PCE using more sensitive biochemical techniques and robust statistical comparisons; 2) more closely examine interindividual variability in the relationship between toxicokinetics and toxicodynamics for TCE and PCE; 3) elucidate the effect of coexposure to these two toxicants; and 4) explore new mechanisms for target organ toxicity associated with TCE and/or PCE exposure.

Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control.

We conducted a random-effects meta-analysis of 50 publications assessing the relationship between oral/oropharyngeal cancer and chewing betel quid, with (BQ+T) or without added tobacco (BQ-T), a common practice in many parts of Asia and globally among Asian immigrants. Exposure-response, by daily amount and years of BQ chewed, was assessed using spline models. Attributable fractions (PAF%) were calculated to estimate the public health impact if BQ were no longer chewed. The meta-relative risk (mRR) for oral/oropharyngeal cancer in the Indian subcontinent was 2.56 (95%CI, 2.00-3.28; 15 studies) for BQ-T and 7.74 (95%CI, 5.38-11.13; 31 studies) for BQ+T; in Taiwan, China, the mRR for BQ-T was 10.98 (95%CI, 4.86-24.84; 13 studies). Restricting to studies that adjusted for tobacco and alcohol use had only a small effect on the risk estimates. For BQ+T in the Indian subcontinent, the mRR was much higher in women (mRR, 14.56; 95%CI, 7.63-27.76) than in men. Exposure-response analyses showed that the risk of oral/oropharyngeal cancer increased with increasing daily amount and duration (years) of chewing BQ in India and Taiwan, China. Roughly half of oral cancers in these countries could be prevented if BQ were no longer chewed (PAF%=53.7% for BQ-T in Taiwan, China; PAF%=49.5% for BQ+T in India). We demonstrate that betel quid chewing, with or without added tobacco, increases the risk of oral/oropharyngeal cancer in an exposure-dependent manner, independently of tobacco and alcohol use. Further work is needed to explain the higher risks associated with chewing BQ-T in Taiwan, China.

Variation in xenobiotic transport and metabolism genes, household chemical exposures, and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk. METHODS: We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures. RESULTS: We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively. CONCLUSIONS: Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants.

The role of alcohol dehydrogenase genes in head and neck cancers: a systematic review and meta-analysis of ADH1B and ADH1C.

Alcohol drinking is a major risk factor for head and neck cancer (HNC). This risk may be modified by alcohol dehydrogenase (ADH) genes, particularly ADH1B and ADH1C, that oxidise ethanol to its carcinogenic metabolite, acetaldehyde. A meta-analysis was conducted to assess the association between ADH1B and ADH1C and HNC risk. Twenty-nine studies from 28 articles identified from a literature search were included. Summary odds ratios (meta-ORs) were generated using random effect models. A reduced risk for HNC was associated with carrying the ADH1B*2 and ADH1C*1 alleles that confer faster metabolism of ethanol to acetaldehyde [meta-OR ADH1B, 0.50; 95% confidence interval (CI): 0.37-0.68, 13 studies; meta-OR ADH1C, 0.87; 95% CI: 0.76-0.99, 22 studies]. ADH1B*2 and ADH1C*1 alleles appear to be protective for HNC, possibly due to: (i) decreasing the opportunity for oral microflora to produce acetaldehyde locally from a prolonged systemic circulation of ethanol, (ii) preventing ethanol from acting as a solvent for other carcinogens, and (iii) decreasing the amount of ethanol a person consumes since a consequent peak in systemic acetaldehyde could cause discomfort. These results underscore the importance of ADH1B and ADH1C in the association between alcohol consumption and the risk for HNC.

The effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are the producers of the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). Welding fumes have been classified as carcinogenic to humans (Group 1) by the WHO International Agency for Research on Cancer (IARC) in IARC Monograph 118; this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus, and lung cancer attributable to occupational exposure to welding fumes, to inform the development of WHO/ILO Joint Estimates on this burden of disease (if considered feasible). OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of any (or high) occupational exposure to welding fumes, compared with no (or low) occupational exposure to welding fumes, on trachea, bronchus, and lung cancer (three outcomes: prevalence, incidence, and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CENTRAL and CISDOC. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but excluded children (<15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies, and other non-randomized intervention studies with an estimate of the effect of any (or high) occupational exposure to welding fumes, compared with occupational exposure to no (or low) welding fumes, on trachea, bronchus, and lung cancer (prevalence, incidence, and mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. If studies reported odds ratios, these were converted to risk ratios (RRs). We combined all RRs using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence, and strength of evidence, using the Navigation Guide tools and approaches adapted to this project. Subgroup (e.g., by WHO region and sex) and sensitivity analyses (e.g., studies judged to be of "high"/"probably high" risk of bias compared with "low"/"probably low" risk of bias) were conducted. RESULTS: Forty-one records from 40 studies (29 case control studies and 11 cohort studies) met the inclusion criteria, comprising over 1,265,512 participants (≥22,761 females) in 21 countries in three WHO regions (Region of the Americas, European Region, and Western Pacific Region). The exposure and outcome were generally assessed by job title or self-report, and medical or administrative records, respectively. Across included studies, risk of bias was overall generally probably low/low, with risk judged high or probably high for several studies in the domains for misclassification bias and confounding. Our search identified no evidence on the outcome of having trachea, bronchus, and lung cancer (prevalence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk of acquiring trachea, bronchus, and lung cancer (incidence) by an estimated 48 % (RR 1.48, 95 % confidence interval [CI] 1.29-1.70, 23 studies, 57,931 participants, I2 24 %; moderate quality of evidence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk dying from trachea, bronchus, and lung cancer (mortality) by an estimated 27 % (RR 1.27, 95 % CI 1.04-1.56, 3 studies, 8,686 participants, I2 0 %; low quality of evidence). Our subgroup analyses found no evidence for difference by WHO region and sex. Sensitivity analyses supported the main analyses. CONCLUSIONS: Overall, for incidence and mortality of trachea, bronchus, and lung cancer, we judged the existing body of evidence for human data as "sufficient evidence of harmfulness" and "limited evidence of harmfulness", respectively. Occupational exposure to welding fumes increased the risk of acquiring and dying from trachea, bronchus, and lung cancer. Producing estimates for the burden of trachea, bronchus, and lung cancer attributable to any (or high) occupational exposure to welding fumes appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates. PROTOCOL IDENTIFIER: https://doi.org/10.1016/j.envint.2020.106089.

Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Lung Cancer Risk: Results from a Pooled Analysis of Case-Control Studies (SYNERGY).

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAH) occurs widely in occupational settings. We investigated the association between occupational exposure to PAH and lung cancer risk and joint effects with smoking within the SYNERGY project. METHODS: We pooled 14 case-control studies with information on lifetime occupational and smoking histories conducted between 1985 and 2010 in Europe and Canada. Exposure to benzo[a]pyrene (BaP) was used as a proxy of PAH and estimated from a quantitative general population job-exposure matrix. Multivariable unconditional logistic regression models, adjusted for smoking and exposure to other occupational lung carcinogens, estimated ORs, and 95% confidence intervals (CI). RESULTS: We included 16,901 lung cancer cases and 20,965 frequency-matched controls. Adjusted OR for PAH exposure (ever) was 1.08 (CI, 1.02-1.15) in men and 1.20 (CI, 1.04-1.38) in women. When stratified by smoking status and histologic subtype, the OR for cumulative exposure ≥0.24 BaP µg/m3-years in men was higher in never smokers overall [1.31 (CI, 0.98-1.75)], for small cell [2.53 (CI, 1.28-4.99)] and squamous cell cancers [1.33 (CI, 0.80-2.21)]. Joint effects between PAH and smoking were observed. Restricting analysis to the most recent studies showed no increased risk. CONCLUSIONS: Elevated lung cancer risk associated with PAH exposure was observed in both sexes, particularly for small cell and squamous cell cancers, after accounting for cigarette smoking and exposure to other occupational lung carcinogens. IMPACT: The lack of association between PAH and lung cancer in more recent studies merits further research under today's exposure conditions and worker protection measures.

Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia.

OBJECTIVE: Folate is involved in the one-carbon metabolism that plays an essential role in the synthesis, repair, and methylation of DNA. We examined whether child's germline genetic variation in the folate pathway is associated with childhood acute lymphoblastic leukemia (ALL), and whether periconception maternal folate and alcohol intake modify the risk. METHODS: Seventy-six single nucleotide polymorphisms (SNPs), including 66 haplotype-tagging SNPs in 10 genes (CBS, DHFR, FOLH1, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS), were genotyped in 377 ALL cases and 448 controls. Log-additive associations between genotypes and ALL risk were adjusted for age, sex, Hispanic ethnicity (when appropriate), and maternal race. RESULTS: Single and haplotype SNPs analyses showed statistically significant associations between SNPs located in (or adjacent to) CBS, MTRR, TYMS/ENOFS, and childhood ALL. Many regions of CBS were associated with childhood ALL in Hispanics and non-Hispanics (p < 0.01). Levels of maternal folate intake modified associations with SNPs in CBS, MTRR, and TYMS. CONCLUSION: Our data suggest the importance of genetic variability in the folate pathway and childhood ALL risk.

Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes. METHODS: We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002. RESULTS: We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL. CONCLUSIONS: These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis.

The IARC Monographs on the carcinogenicity of crystalline silica.

BACKGROUND: Through extensive review of the published literature, two independent expert panels convened by the International Agency for Research on Cancer (IARC) Monographs Programme have classified crystalline silica as carcinogenic to humans while amorphous silica was not classifiable as to its carcinogenicity in humans. The panel remarked that crystalline silica in the form of quartz or cristobalite dust causes lung cancer in humans. OBJECTIVES: We discuss the literature and rationale used to support the IARC evaluations of silica. METHODS: A critical review, with a focus on lung tumors, was conducted of the pertinent literature on the carcinogenic effects of crystalline silica in humans and experimental animals as well as supportive mechanistic evidence. RESULTS: The strongest supportive evidence comes from pooled and meta-analyses that employed quantitative exposure assessment, focused on silicotics, accounted for potential confounding and demonstrated exposure-response trends. Consistency of the effect was observed despite some heterogeneity between individual studies. Tumor site concordance was observed with rodents and further supported by mechanistic data. CONCLUSIONS: Several million workers worldwide are exposed to crystalline silica. Silicosis and lung cancer in these workers are completely preventable diseases. The IARC evaluations are critical to supporting public health interventions to protect persons at high-risk.