International Agency For Research On Cancer Evaluation Research Articles

The carcinogenicity of opium consumption: a systematic review and meta-analysis

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding.In total, 2 prospective cohort studies and 33 case–control studies were included. The overall pooled mRR estimated for ‘ever or regular’ versus ‘never’ use of opium ranged from 1.50 (95% CI 1.13–1.99, I2 = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79–13.3, I2 = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.

The history of compensation system for workers with pneumoconiosis-related lung cancer

To review the historical aspects of compensation system for workers with pneumoconiosis who developed lung cancer. Materials and papers published on the compensation system as discussed in administrative meetings were utilized. Legal claims for compensation for lung cancer among individuals with pneumoconiosis increased during the period of rapid economic growth in Japan. A possible causal relationship between pneumoconiosis and lung cancer in workers has been discussed by committees of specialists. The Expert Committee on Pneumoconiosis and Lung Cancer in 1978 did not find a causal relationship between them. However, a survey of physicians specializing in pneumoconiosis revealed medical disadvantages among individuals diagnosed with pneumoconiosis who developed lung cancer. The Ministry of Labour announced the risk of work-related lung cancer in patients with advanced pneumoconiosis (class IV or equivalent severity). Since then, numerous lung cancer patients with pneumoconiosis have been adjudicated. In 1997, the International Agency for Research on Cancer (IARC) re-evaluated the carcinogenicity of silica and declared it to be a Group I carcinogen in humans. The Expert Committee on Compensation of Lung Cancer Cases Developing from Pneumoconiosis discussed the IARC evaluation but did not accept this classification. However, the Committee of Occupational Exposure Limits in the Japan Society of Occupational Health upheld the IARC evaluation of silica as a Group I carcinogen. Because the Expert Committee of Medical Disadvantage of Lung Cancer Patients with Pneumoconiosis accepted the increased risk of lung cancer in patients with class III or equivalent severity pneumoconiosis, the Ministry of Labour announced worker compensation for such patients. The Expert Committee of Health Control of Pneumoconiosis Complicated with Lung Cancer reported in 2002 that a meta-analysis revealed no increased risk of lung cancer among workers exposed to crystalline silica; however, there was an increased risk of lung cancer in patients with pneumoconiosis. The Ministry of Labour has added lung cancer to the list of complications from pneumoconiosis and, if necessary, regular medical checkups for lung cancer. After Leaving dust work, the Health Care System provides for workers who are diagnosed With class II or higher pneumoconiosis. Therefore, if an individual with pneumoconiosis develops class II or higher lung cancer, that individual becomes eligible for workers' compensation. The conclusion of the Expert Committee in 2002 and the decision of the Ministry of Labour to add lung cancer to its list of complications of pneumoconiosis are evaluated to be appropriate.

Lung cancer risk in never-smokers: An overview of environmental and genetic factors.

Lung cancer is the leading cause of cancer-related mortality globally, accounting for 1.8 million deaths in 2020. While the vast majority are caused by tobacco smoking, 15%−25% of all lung cancer cases occur in lifelong never-smokers. The International Agency for Research on Cancer (IARC) has classified multiple agents with sufficient evidence for lung carcinogenesis in humans, which include tobacco smoking, as well as several environmental exposures such as radon, second-hand tobacco smoke, outdoor air pollution, household combustion of coal and several occupational hazards. However, the IARC evaluation had not been stratified based on smoking status, and notably lung cancer in never-smokers (LCINS) has different epidemiological, clinicopathologic and molecular characteristics from lung cancer in ever-smokers. Among several risk factors proposed for the development of LCINS, environmental factors have the most available evidence for their association with LCINS and their roles cannot be overemphasized. Additionally, while initial genetic studies largely focused on lung cancer as a whole, recent studies have also identified genetic risk factors for LCINS. This article presents an overview of several environmental factors associated with LCINS, and some of the emerging evidence for genetic factors associated with LCINS. An increased understanding of the risk factors associated with LCINS not only helps to evaluate a never-smoker’s personal risk for lung cancer, but also has important public health implications for the prevention and early detection of the disease. Conclusive evidence on causal associations could inform longer-term policy reform in a range of areas including occupational health and safety, urban design, energy use and particle emissions, and the importance of considering the impacts of second-hand smoke in tobacco control policy.

Managing Occupational Exposure to Welding Fume: New Evidence Suggests a More Precautionary Approach is Needed.

Welding is a common industrial process with many millions of workers exposed worldwide. In October 2017, the International Agency for Research on Cancer (IARC) concluded that exposure to welding fumes causes lung cancer in humans, based primarily on the available epidemiological literature. These research studies did not show that the cancer risk differed between mild steel and stainless steel welding but were related to the total welding aerosol. Lung cancer risks were observable at very low exposure levels; below 1 mg m-3 and perhaps as low as 0.1 mg m-3, averaged over a working lifetime. As a result of this IARC evaluation, in Britain, the Health and Safety Executive has acted to strengthen its enforcement expectations for fume control at welding activities. In the light of these developments, it would seem appropriate to review current health-based exposure limits for metal dust and fumes from welding to ensure they are protective.

Public health and evidence-informed policy-making: The case of a commonly used herbicide.

Public health and evidence-informed policy-making: The case of a commonly used herbicide.

Night Shift Work and Risk of Breast Cancer

Night work is increasingly common and a necessity in certain sectors of the modern 24-h society. The embedded exposure to light-at-night, which suppresses the nocturnal hormone melatonin with oncostatic properties and circadian disruption, i.e., misalignment between internal and external night and between cells and organs, are suggested as main mechanisms involved in carcinogenesis. In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as probably carcinogenic to humans based on limited evidence from eight epidemiologic studies on breast cancer, in addition to sufficient evidence from animal experiments. The aim of this review is a critical update of the IARC evaluation, including subsequent and the most recent epidemiologic evidence on breast cancer risk after night work. After 2007, in total nine new case-control studies, one case-cohort study, and eight cohort studies are published, which triples the number of studies. Further, two previous cohorts have been updated with extended follow-up. The assessment of night shift work is different in all of the 26 existing studies. There is some evidence that high number of consecutive night shifts has impact on the extent of circadian disruption, and thereby increased breast cancer risk, but this information is missing in almost all cohort studies. This in combination with short-term follow-up of aging cohorts may explain why some cohort studies may have null findings. The more recent case-control studies have contributed interesting results concerning breast cancer subtypes in relation to both menopausal status and different hormonal subtypes. The large differences in definitions of both exposure and outcome may contribute to the observed heterogeneity of results from studies of night work and breast cancer, which overall points in the direction of an increased breast cancer risk, in particular after over 20years of night shifts. Overall, there is a tendency of increased risk of breast cancer either after over 20years of night shift or after shorter periods with many consecutive shifts. More epidemiologic research using standardized definitions of night work metrics and breast cancer subtypes as well as other cancers is needed in order to improve the epidemiologic evidence in combination with animal models of night work. Also, evidence-based preventive interventions are needed.

IARC use of oxidative stress as key mode of action characteristic for facilitating cancer classification: Glyphosate case example illustrating a lack of robustness in interpretative implementation

The International Agency for Research on Cancer (IARC) has formulated 10 key characteristics of human carcinogens to incorporate mechanistic data into cancer hazard classifications. The analysis used glyphosate as a case example to examine the robustness of IARC's determination of oxidative stress as “strong” evidence supporting a plausible cancer mechanism in humans. The IARC analysis primarily relied on 14 human/mammalian studies; 19 non-mammalian studies were uninformative of human cancer given the broad spectrum of test species and extensive use of formulations and aquatic testing. The mammalian studies had substantial experimental limitations for informing cancer mechanism including use of: single doses and time points; cytotoxic/toxic test doses; tissues not identified as potential cancer targets; glyphosate formulations or mixtures; technically limited oxidative stress biomarkers. The doses were many orders of magnitude higher than human exposures determined in human biomonitoring studies. The glyphosate case example reveals that the IARC evaluation fell substantially short of “strong” supporting evidence of oxidative stress as a plausible human cancer mechanism, and suggests that other IARC monographs relying on the 10 key characteristics approach should be similarly examined for a lack of robust data integration fundamental to reasonable mode of action evaluations.

Prevention of disease caused by fluoro-edenite fibrous amphibole: the way forward.

Few months after the publication of the monographic section of Annali dell'Istituto Superiore di Sanità second issue of 2014 "Health impact of fibres with fluoro-edenitic composition", the carcinogenicity of fluoro-edenite was assessed by the International Agency for Research on Cancer (IARC) in the frame of Monograph 111. The IARC Working Group concluded that there is sufficient evidence in humans that exposure to fluoro-edenite fibrous amphibole causes mesothelioma, and sufficient evidence of carcinogenicity in experimental animals. Fluoro-edenite was allocated to Group 1 (the agent is carcinogenic to humans). Now, in view of the recent IARC evaluation, preventive action in Biancavilla requires an upgrade. First of all, environmental monitoring has to be further implemented. All operations of house cleaning should be performed employing wet tools, in order to avoid dust-raising. It is very important that environmental and biological monitoring be related to epidemiological surveillance. The recently approved act of the Sicilian Government concerning a plan of health interventions in Biancavilla will favour cooperation between national, regional and local health institutions with the common goal of improving the quality and appropriateness of diagnostic and therapeutics procedures offered by the health services.

Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis.

Background: Particulate matter (PM) in outdoor air pollution was recently designated a Group I carcinogen by the International Agency for Research on Cancer (IARC). This determination was based on the evidence regarding the relationship of PM2.5 and PM10 to lung cancer risk; however, the IARC evaluation did not include a quantitative summary of the evidence.Objective: Our goal was to provide a systematic review and quantitative summary of the evidence regarding the relationship between PM and lung cancer.Methods: We conducted meta-analyses of studies examining the relationship of exposure to PM2.5 and PM10 with lung cancer incidence and mortality. In total, 18 studies met our inclusion criteria and provided the information necessary to estimate the change in lung cancer risk per 10-μg/m3 increase in exposure to PM. We used random-effects analyses to allow between-study variability to contribute to meta-estimates.Results: The meta-relative risk for lung cancer associated with PM2.5 was 1.09 (95% CI: 1.04, 1.14). The meta-relative risk of lung cancer associated with PM10 was similar, but less precise: 1.08 (95% CI: 1.00, 1.17). Estimates were robust to restriction to studies that considered potential confounders, as well as subanalyses by exposure assessment method. Analyses by smoking status showed that lung cancer risk associated with PM2.5 was greatest for former smokers [1.44 (95% CI: 1.04, 2.01)], followed by never-smokers [1.18 (95% CI: 1.00, 1.39)], and then current smokers [1.06 (95% CI: 0.97, 1.15)]. In addition, meta-estimates for adenocarcinoma associated with PM2.5 and PM10 were 1.40 (95% CI: 1.07, 1.83) and 1.29 (95% CI: 1.02, 1.63), respectively.Conclusion: The results of these analyses, and the decision of the IARC Working Group to classify PM and outdoor air pollution as carcinogenic (Group 1), further justify efforts to reduce exposures to air pollutants that can arise from many sources.Citation: Hamra GB, Guha N, Cohen A, Laden F, Raaschou-Nielsen O, Samet JM, Vineis P, Forastiere F, Saldiva P, Yorifuji T, Loomis D. 2014. Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis. Environ Health Perspect 122:906–911; http://dx.doi.org/10.1289/ehp.1408092

0314 Using meta-data from occupational studies to inform hazard identification and cancer control: the IARC Monographs and beyond0314 Using meta-data from occupational studies to inform hazard identification and cancer control: the IARC Monographs and beyond

ObjectivesTo present extensions to the International Agency for Research on Cancer (IARC) Monographs process, providing examples of application of meta-data to identifying carcinogenic hazard identifications and research gaps, and the...

Carcinogenic potential of formaldehyde in occupational settings: a critical assessment and possible impact on occupational exposure levels

To review epidemiological studies which led to a change in the classification of formaldehyde by the International Agency for Research on Cancer (IARC) in 2004 as well as studies published thereafter, with the objective to examine whether occupational exposure levels for formaldehyde should be adapted. Cohort and case-control studies investigating the association between occupational exposure to formaldehyde and nasopharyngeal cancer (NPC) and reporting estimates of formaldehyde exposure as well as the most recent meta-analyses, published after 1994, were reviewed. Evidence of an association between occupational formaldehyde exposure and NPC appears debatable. Results of the cohort studied by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) were key findings in the IARC evaluation. In this study, mortality from NPC was elevated compared with that of the US general population. However, internal comparison analysis using alternative categorization revealed that none of the relative risk for NPC was statistically significantly increased in any category of exposure (Marsh and Youk in Regul Toxicol Pharmacol 42(3):275-283, 2005) and re-analyses of the data highlighted the inappropriateness of the exposure assessment used by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) and Marsh et al. (Regul Toxicol Pharmacol 47(1):59-67, 2007). Two other cohorts (Coggon et al. in J Natl Cancer Inst 95(21):1608-1615, 2003; Pinkerton et al. in Occup Environ Med 61(3)193-200, 2004) reported no increase in NPC. Two case-control studies brought some evidence of an increased risk of NPC but the assessment of exposure levels was uncertain. Human studies fail to raise a convincing conclusion concerning the carcinogenicity of formaldehyde and are not helpful to delineate a possible dose-response relationship. Experimental data indicate that in rats, the carcinogenic activity of formaldehyde is associated with cytotoxic/proliferative mechanisms. Therefore protecting from these effects associated with formaldehyde exposure should be sufficient to protect from its potential carcinogenic effects, if any in humans. Current occupational exposure levels to formaldehyde, set to protect against local irritation, should not be adapted.

Folgerungen der IARC-Neubewertung von alkoholischen Getränken und Ethylcarbamat für die Lebensmittelüberwachung

In February 2007, the International Agency for Research on Cancer (IARC) has reassessed the carcinogenicity of alcoholic beverages within its monographs programme. Ethanol in alcoholic beverages was classified as to humans (Group 1). Many studies have consistently shown that regular alcohol consumption is causally related with an increased risk for cancer of the oral cavity, pharynx, larynx, oesophagus, liver, female breast and colorectum. In contrast to the previous evaluation of alcohol drinking in 1988, the IARC working group found evidence that ethanol and not other constituents or contaminants cause the carcinogenicity. In general, the risk for cancer increases with the amount of alcohol intake, e.g. the daily consumption of around 50 g of alcohol increases the risk of cancer of the oral cavity three-fold, compared to the risk of non-drinkers. An association with different types of alcoholic beverages (beer, wine, or spirits) was not observed. A separate evaluation was made for ethyl carbamate (urethane), a frequent contaminant of fermented foods and beverages. Ethyl carbamate was upgraded into Group 2A (probably carcinogenic to humans). The IARC evaluations emphasize the importance and necessity of avoiding and of controling further carcinogenic contaminants in alcoholic beverages (besides ethyl carbamate, e.g. nitrosamines, mycotoxins, lead, cadmium, arsenic), as there exists the possibility of synergistic effects on carcinogenicity between ethanol and other contaminants. In consideration of the IARC evaluation of alcohol as carcinogenic, the EU Health Claims Regulation is appreciated for its prohibiton of nutrition or health claims in the labelling of alcoholic beverages. Furthermore, the proposals for warning labels on alcoholic beverages similar to those on tobacco products are discussed.

An IARC evaluation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans as risk factors in human carcinogenesis.

The International Agency for Research on Cancer (IARC) Monographs program reevaluated polychlorinated dibenzo-p-dioxins and evaluated polychlorinated dibenzofurans as possible carcinogenic hazards to humans in February 1997, using the most recent epidemiologic data on exposed human populations, experimental carcinogenicity bioassays in laboratory animals, and supporting evidence on relevant mechanisms of carcinogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was evaluated as carcinogenic to humans (IARC group 1 classification) on the basis of limited evidence of carcinogenicity to humans derived from follow-up of workers who had been heavily exposed in industrial accidents and sufficient evidence of carcinogenicity in experimental animals. The evaluation also considered the following supporting evidence: TCDD is a multisite carcinogen in experimental animals and has been shown by several lines of evidence to act through a mechanism involving the aryl hydrocarbon receptor; this receptor is highly conserved in an evolutionary sense and functions the same way in humans as in experimental animals; tissue concentrations of TCDD are similar in heavily exposed human populations in which an increased overall cancer risk was observed and in exposed rats that developed tumors in carcinogenicity tests. Other polychlorinated dibenzo-p-dioxins, the nonchlorinated dibenzo-p-dioxin, and polychlorinated dibenzofurans were evaluated as not classifiable as to their carcinogenicity to humans (group 3).