Enzo Merler

Sinonasal cancer and occupational exposures: a pooled analysis of 12 case-control studies

Objective: In order to examine the associations between sinonasal cancer and occupational exposures other than wood dust and leather dust, the data from 12 case–control studies conducted in seven countries were pooled and reanalyzed. Methods: The pooled data set included 195 adenocarcinoma cases (169 men and 26 women), 432 squamous cell carcinomas (330 men and 102 women), and 3136 controls (2349 men and 787 women). Occupational exposures to formaldehyde, silica dust, textile dust, coal dust, flour dust, asbestos, and man-made vitreous fibers were assessed with a job-exposure matrix. Odds ratios (ORs) were adjusted for age, study, wood dust, and leather dust, or other occupational exposures when relevant. 95% confidence intervals (CIs) were estimated by unconditional logistic regression. Results: A significantly increased risk of adenocarcinoma was associated with exposure to formaldehyde. The ORs for the highest level of exposure were 3.0 (CI = 1.5–5.7) among men and 6.2 (CI = 2.0–19.7) among women. An elevated risk of squamous cell carcinoma was observed among men (OR = 2.5, CI = 0.6–10.1) and women (OR = 3.5, CI = 1.2–10.5) with a high probability of exposure to formaldehyde. Exposure to textile dust was associated with non-significantly elevated risk of adenocarcinoma, among women only: the OR for the high level of cumulative exposure was 2.5 (CI = 0.7–9.0). High level of asbestos exposure was associated with a significantly increased risk of squamous cell carcinoma among men (OR = 1.6, CI = 1.1–2.3). Conclusions: The results of this pooled analysis support the hypothesis that occupational exposure to formaldehyde increases the risk of sinonasal cancer, particularly of adenocarcinoma. They also indicate an elevated risk of adenocarcinoma among women exposed to textile dust, and suggest that exposure to asbestos may increase the risk of squamous cell carcinoma.

Sinonasal cancer, occupation, and tobacco smoking in European women and men

BACKGROUND In this analysis of European case-control studies on sinonasal cancer, we examined the risk for occupation and smoking, by gender and histological type. METHODS The pooled data included 104 female and 451 male cases, and 241 female and 1,464 male controls. Lifetime smoking and occupational history were recoded following uniform criteria, and job-exposure matrices were applied for wood and leather dust. RESULTS Wood dust exposure was associated with an excess risk in men (OR = 2.36, 95% CI 1.75-3.2) but not in women (OR = 1.17, 95% CI 0.31-4.47). Exposure to leather dust was associated with an excess risk in both genders. Both wood and leather dust were associated with adenocarcinomas rather than squamous cell carcinomas. Excess risks for smoking were higher for squamous cell carcinomas and higher in men than in women. CONCLUSIONS In these European populations, occupation was associated with about 11% of all sinonasal cancers in women and 39% in men. This difference can, in part, be attributed to variation in exposure patterns between genders.

Pleural mesothelioma incidence in Europe: Evidence of some deceleration in the increasing trends

Objective: To summarize the geographical and temporal variations in incidence of pleural mesothelioma in Europe, using the extensive data available from European general cancer registries, and consider these in light of recent trends in asbestos extraction, use and import in European countries. Material and methods: The data were extracted from the European Cancer Incidence and Mortality database (EUROCIM). The inclusion criteria was acceptance in Volume VII of Cancer Incidence in Five Continents. Truncated age-standardized rates per 100,000 for the ages 40–74 were used to summarise recent geographical variations. Standardized rate ratios and 95% confidence intervals for the periods 1986–1990 and 1991–1995 were compared to assess geographical variations in risk. To investigate changes in the magnitude of most recent trends, regression models fitted to the latest available 10-year period (1988–1997) were compared with trends in the previous decade. Fitted rates in younger (40–64) and older adults (65–74) in the most recent period were also compared. Results: There was a great deal of geographical variation in the risk of mesothelioma, annual rates ranging from around 8 per 100,000 in Scotland, England and The Netherlands, to lower than 1 per 100,000 in Spain (0.96), Estonia (0.85), Poland (0.85) and Yugoslavia, Vojvodina (0.56) among men. The rank of the rates for women was similar to that observed for men, although rates were considerably lower. Between 1978 and 1987, rates in men significantly increased in all countries (excepting Denmark). In the following 10 years, there was a deceleration in trend, and a significant increase was detectable only in England and France. In addition, the magnitude of recent trends in younger men was generally lower than those estimated for older men, in both national and regional cancer registry settings. Conclusions: While mesothelioma incidence rates are still rising in Europe, a deceleration has started in some countries. A decrease may begin in the next few years in certain European populations considering the deceleration of observed trends in mesothelioma and asbestos exposure, as well as the recent ban on its use.

Survival of peritoneal malignant mesothelioma in Italy: a population-based study.

In some population‐based studies, a shorter median survival was observed in peritoneal as compared with pleural, malignant mesothelioma, but in others, longer median survival times or higher proportions of long‐term survivors were reported. Statistical instability could have caused these differences. We analyzed survival in peritoneal mesothelioma in a large and unselected population‐based case series. Cases (338) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan‐Meier) and multivariate (Cox proportional hazards regression) analyses of survival were performed according to selected individual characteristics, including limited treatment information in a subset of 194 cases. The results were compared with those obtained in a parallel study on pleural mesothelioma cases. Epithelioid histotype, younger age at diagnosis and, to a lesser degree, gender (women), and being diagnosed in a hospital with a thoracic surgery unit positively and significantly affected survival. The effect of treatment was positive but not statistically significant. No trend in the risk of death according to calendar period of diagnosis was present. Peritoneal mesothelioma cases had shorter median survival time than pleural cases, but a larger proportion of long‐term survivors. Survival patterns after peritoneal and pleural mesothelioma differed markedly. Treatment was not associated with a statistically significant improvement in survival, but our study included cases first diagnosed before the introduction of the most recent therapeutic approaches. This provides a large historical comparison for future studies on survival trends at the population level.

Malignant pleural and peritoneal mesotheliomas in former miners and millers of crocidolite at Wittenoom, Western Australia

Aims: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2000, and to compare this with earlier predictions. Methods: A group of 6493 men and 415 women who had worked at the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2000. Results: The cumulative number of mesotheliomas up to 2000 was 235 in men (202 pleural, 33 peritoneal) and seven (all pleural) in women. There had been 231 deaths with mesothelioma (9% of known deaths). Conclusions: The number of deaths in men with mesothelioma between 1987 and 2000 was at the low end of the predictions made earlier based on the number of cases to 1986. If this trend continues, it is predicted that about another 110 deaths with mesothelioma will occur in men by 2020.

Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register.

Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992), a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004, a case‐list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardized incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N = 4,577 cases), while 4.4% was due to cohabitation with someone (generally, the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group, 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers, the median year of first exposure was 1957, and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signaled as “at risk” (asbestos‐cement industry, shipbuilding and repair and railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all‐too‐predictable asbestos effects should be transferred to developing countries where asbestos use is spreading.

Mortality from cardiovascular diseases and exposure to inorganic mercury

OBJECTIVE To study the mortality from cardiovascular and other chronic non-neoplastic diseases after long term exposure to inorganic mercury. Limited information is available on the effect of chronic exposure to mercury on the cardiovascular system. METHODS The mortality was studied among 6784 male and 265 female workers from four mercury mines and mills in Spain, Slovenia, Italy, and the Ukraine. Workers were employed between 1900 and 1990; the follow up period lasted from the 1950s to the 1990s. The mortality of the workers was compared with national reference rates. RESULTS Among men, there was a slight increase in overall mortality (standardised mortality ratio (SMR) 1.08, 95% confidence interval (95% CI) 1.04 to 1.12). An increased mortality was found from hypertension (SMR 1.46, 95% CI 1.08 to 1.93), heart diseases other than ischaemic (SMR 1.36, 95% CI 1.20 to 1.53), pneumoconiosis (SMR 27.1, 95% CI 23.1 to 31.6), and nephritis and nephrosis (SMR 1.55, 95% CI 1.13 to 2.06). The increase in mortality from cardiovascular diseases was not consistent among countries. Mortality from hypertension and other heart diseases increased with estimated cumulative exposure to mercury; mortality from ischaemic heart disease and cerebrovascular diseases increased with duration of employment, but not with estimated exposure to mercury. Results among women were hampered by few deaths. CONCLUSION Despite limited quantitative data on exposure, possible confounding, and likely misclassification of disease, the study suggests a possible association between employment in mercury mining and refining and risk in some groups of cardiovascular diseases.

Mesothelioma risk after 40 years since first exposure to asbestos: a pooled analysis

Background The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40 years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time. Methods The data from six cohort studies of exposed workers and two cohorts with residential exposure have been pooled. A nested case control design matched cases and controls on calendar period and age. Conditional logistic regression modelled the relationship between time since first exposure and risk of MM. Results The combined data consisted of 22 048 people with asbestos exposure (5769 women), 707 cases of pleural MM (165 in women) and 155 cases of peritoneal MM (32 in women). Median time since first exposure for pleural MM cases was 38.4 years (IQR 31.3–45.3). Median duration of exposure for pleural MM cases was 3.75 years (IQR 0.7–18.2). The rate and risk of pleural MM increased until 45 years following first exposure and then appeared to increase at a slower power of time since first exposure. The rate of increase in peritoneal MM over the 10–50 years since first exposure continued to increase. Conclusions Exposure to asbestos confers a long-term risk of developing pleural and peritoneal mesothelioma which increases following cessation of exposure. While the rate of increase appears to start to level out after 40–50 years no one survives long enough for the excess risk to disappear.

Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case–control study

AbstractObjective:To discover whether tobacco smoking and intake of different types of alcoholic drinks are associated with small bowel adenocarcinoma (SBA). Methods:A population-based European multi-center case–control study was conducted from 1995 to 1997. Results:After a histological review using uniform diagnostic criteria, 47 (33%) of the 142 identified cases of SBA were excluded due to reclassification as either tumors of the papilla of Vater (n = 22), stromal tumors, or metastases; 95 cases were accepted for study. In all, 70 cases of SBA together with 2070 controls matched by age, sex, and region were interviewed. A high intake (more than 24 g alcohol per day) of beer or spirits was associated with SBA, an odds ratio (OR) of 3.5 and 95% confidence intervals (CI) of 1.5–8.0 and 3.4 (95% CI 1.3–9.2), respectively). There was no association with wine intake or total alcohol intake. Tobacco smoking was probably unrelated to SBA. Conclusions:A high intake of beer or spirits seems to be a risk factor for SBA. Since this association was not seen for wine drinkers, protective components of wine may counterbalance a carcinogenic effect of alcohol on the small bowel. Alternatively, the result may be confounded by other factors, e.g. dietary factors.

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substances potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen . The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ‘glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential’. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected. EFSA concluded ‘that there is very limited evidence for an association between glyphosate-based formulations …