The IARC Monographs: Updated Procedures for Modern and Transparent Evidence Synthesis in Cancer Hazard Identification.

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.

Exploring causality of the association between smoking and Parkinson's disease.

BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.

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.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study.

OBJECTIVE: To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN: Multicentre case-cohort study. SETTING: A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS: 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES: Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS: There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS: Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.

The hazards of hazard identification in environmental epidemiology.

Hazard identification is a major scientific challenge, notably for environmental epidemiology, and is often surrounded, as the recent case of glyphosate shows, by debate arising in the first place by the inherently problematic nature of many components of the identification process. Particularly relevant in this respect are components less amenable to logical or mathematical formalization and essentially dependent on scientists' judgment. Four such potentially hazardous components that are capable of distorting the correct process of hazard identification are reviewed and discussed from an epidemiologist perspective: (1) lexical mix-up of hazard and risk (2) scientific questions as distinct from testable hypotheses, and implications for the hierarchy of strength of evidence obtainable from different types of study designs (3) assumptions in prior beliefs and model choices and (4) conflicts of interest. Four suggestions are put forward to strengthen a process that remains in several aspects judgmental, but not arbitrary, in nature.

European Code against Cancer 4th Edition: Environment, occupation and cancer.

People are exposed throughout life to a wide range of environmental and occupational pollutants from different sources at home, in the workplace or in the general environment - exposures that normally cannot be directly controlled by the individual. Several chemicals, metals, dusts, fibres, and occupations have been established to be causally associated with an increased risk of specific cancers, such as cancers of the lung, skin and urinary bladder, and mesothelioma. Significant amounts of air pollutants - mainly from road transport and industry - continue to be emitted in the European Union (EU); an increased occurrence of lung cancer has been attributed to air pollution even in areas below the EU limits for daily air pollution. Additionally, a wide range of pesticides as well as industrial and household chemicals may lead to widespread human exposure, mainly through food and water. For most environmental pollutants, the most effective measures are regulations and community actions aimed at reducing and eliminating the exposures. Thus, it is imperative to raise awareness about environmental and occupational carcinogens in order to motivate individuals to be proactive in advocating protection and supporting initiatives aimed at reducing pollution. Regulations are not homogeneous across EU countries, and protective measures in the workplace are not used consistently by all workers all the time; compliance with regulations needs to be continuously monitored and enforced. Therefore, the recommendation on Environment and Occupation of the 4th edition of the European Code against Cancer, focusing on what individuals can do to reduce their cancer risk, reads: "In the workplace, protect yourself against cancer-causing substances by following health and safety instructions."

Population health and status of epidemiology in Western European, Balkan and Baltic countries.

BACKGROUND: This article is part of a series commissioned by the International Epidemiological Association, aimed at describing population health and epidemiological resources in the six World Health Organization (WHO) regions. It covers 32 of the 53 WHO European countries, namely the Western European countries, the Balkan countries and the Baltic countries. METHODS: The burdens of mortality and morbidity and the patterns of risk factors and inequalities have been reviewed in order to identify health priorities and challenges. Literature and internet searches were conducted to stock-take epidemiological teaching, research activities, funding and scientific productivity. FINDINGS: These countries have among the highest life expectancies worldwide. However, within- and between-country inequalities persist, which are largely due to inequalities in distribution of main health determinants. There is a long tradition of epidemiological research and teaching in most countries, in particular in the Western European countries. Cross-national networks and collaborations are increasing through the support of the European Union which fosters procedures to standardize educational systems across Europe and provides funding for epidemiological research through framework programmes. The number of Medline-indexed epidemiological research publications per year led by Western European countries has been increasing. The countries accounts for nearly a third of the global epidemiological publication. CONCLUSIONS: Although population health has improved considerably overall, persistent within- and between-country inequalities continue to challenge national and European health institutions. More research, policy and action on the social determinants of health are required in the region. Epidemiological training, research and workforce in the Baltic and Balkan countries should be strengthened. European epidemiologists can play pivotal roles and must influence legislation concerning production and access to high-quality data.

Environment and cancer: the legacy of Lorenzo Tomatis.

As an introduction to the series of papers arising from the first 'Lorenzo Tomatis Conference on Environment and Cancer' , Tomatis' contributions to research in cancer prevention are first noted, especially the ongoing programme 'IARC Monographs on Carcinogenic Risk for humans' that he established at the International Agency for Research on Cancer' , of which he was the Director from 1982 to 1993. The programme, started in 1972, has become an international authoritative reference and represents an early 'evidence-based' development bringing together a comprehensive evaluation of both experimental and epidemiological data. Next the recurrent issue of how large is the contribution of environmental factors to cancer etiology is examined pointing to the several limitations making estimates of the population fraction of cancers attributable to environment delicate to interpret or sometimes even misleading. Finally mention is made of societal issues such as social inequalities in cancer occurrence and fatality, communication in the clinical oncology and cancer prevention and screening areas and the relation between these and the blossoming basic cancer research boosted by the revolution in molecular biology and genetics.

Second-hand smoke, cotinine levels, and risk of circulatory mortality in a large cohort study of never-smokers.

BACKGROUND: Exposure to second-hand smoke has been shown to be associated with increased cardiovascular mortality in several, but not all, epidemiologic studies. Our aim was to investigate the risk of circulatory death associated with exposure to second-hand smoke in never-smokers in a very large prospective study, the European Prospective Investigation into Cancer and Nutrition. A secondary aim was to use cotinine levels for cross-validating self-reported second-hand smoke exposure. METHODS: Cox proportional hazard models were used to investigate the risk of death due to circulatory causes associated with second-hand smoke exposure in 135,233 never-smokers. Exposure to second-hand smoke was assessed through a questionnaire at enrollment and then validated against plasma cotinine measurements in a subsample. RESULTS: Study participants who reported second-hand smoke exposure at home had higher cotinine levels (median plasma cotinine concentration in exposed = 0.82 microg/L; in those unexposed 0.02 microg/L). Second-hand smoke exposure at home was associated with an increased risk of dying from cardiovascular diseases (hazard ratio [HR] = 1.38 [95% confidence interval = 1.01-1.90]), all circulatory diseases (1.28 [0.98-1.69]), and coronary heart disease (1.31 [0.83-2.08]) after adjustment for age, sex, education, physical activity, and body mass index. Dose-response relationships were observed between exposure to second-hand smoke at home and risk of circulatory death (HR per each additional hour/d = 1.25 [1.04-1.50]). Having a partner who smokes more than 30 cigarettes per day considerably increased the risk of a circulatory death (2.94 [1.11-7.78]). Second-hand smoke exposure at home was not associated with total mortality (1.03 [0.93-1.13]). DISCUSSION: Exposure to second-hand smoke at home (as confirmed by plasma cotinine levels) increases the risk of cardiovascular mortality.

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC.

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by (32)P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 micromol GSH g(-1) haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.

International collaborations in cancer control and the Third International Cancer Control Congress.

Over the past few decades, there has been growing support for the idea that cancer needs an interdisciplinary approach. Therefore, the international cancer community has developed several strategies as outlined in the WHO non-communicable diseases Action Plan (which includes cancer control) as the World Health Assembly and the UICC World Cancer Declaration, which both include primary prevention, early diagnosis, treatment, and palliative care. This paper highlights experiences/ideas in cancer control for international collaborations between low, middle, and high income countries, including collaborations between the European Union (EU) and African Union (AU) Member States, the Latin-American and Caribbean countries, and the Eastern Mediterranean countries. These proposals are presented within the context of the global vision on cancer control set forth by WHO in partnership with the International Union Against Cancer (UICC), in addition to issues that should be considered for collaborations at the global level: cancer survival (similar to the project CONCORD), cancer control for youth and adaptation of Clinical Practice Guidelines. Since cancer control is given lower priority on the health agenda of low and middle income countries and is less represented in global health efforts in those countries, EU and AU cancer stakeholders are working to put cancer control on the agenda of the EU-AU treaty for collaborations, and are proposing to consider palliative care, population-based cancer registration, and training and education focusing on primary prevention as core tools. A Community of Practice, such as the Third International Cancer Control Congress (ICCC-3), is an ideal place to share new proposals, learn from other experiences, and formulate new ideas. The aim of the ICCC-3 is to foster new international collaborations to promote cancer control actions in low and middle income countries. The development of supranational collaborations has been hindered by the fact that cancer control is not part of the objectives of the Millennium Development Goals (MGGs). As a consequence, less resources of development aids are allocated to control NCDs including cancer.