Childhood infectious diseases and risk of multiple myeloma: an analysis of the Italian multicentre case-control study.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph).

BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

Occupational exposure to trichloroethylene and risk of non-Hodgkin lymphoma and its major subtypes: a pooled InterLymph [correction of IinterLlymph] analysis.

OBJECTIVES: We evaluated the association between occupational exposure to trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled analysis of four international case-control studies. METHODS: Overall, the pooled study population included 3788 NHL cases and 4279 controls. Risk of NHL and its major subtypes associated with TCE exposure was calculated with unconditional logistic regression and polytomous regression analysis, adjusting by age, gender and study. RESULTS: Risk of follicular lymphoma (FL), but not NHL overall or other subtypes, increased by probability (p=0.02) and intensity level (p=0.04), and with the combined analysis of four exposure metrics assumed as independent (p=0.004). After restricting the analysis to the most likely exposed study subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01, respectively) and with the combined analysis of duration, frequency and intensity of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B-cell lymphoma, FL and CLL, showed increases in risk ranging 2-3.2-fold in the highest category of exposure intensity. No significant heterogeneity in risk was detected by major NHL subtypes or by study. CONCLUSIONS: Our pooled analysis apparently supports the hypothesis of an increase in risk of specific NHL subtypes associated with occupational exposure to TCE.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

[Epithelial naso-sinusal cancer incidence and the role of work in 100 cases diagnosed in the Province of Brescia (northern Italy), in the period 1978-2002]. / Incidenza dei tumori naso-sinusali epiteliali ed attività lavorative in 100 casi diagnosticati in provincia di Brescia dal 1978 al 2002.

BACKGROUND: Naso-sinusal cancers (NSC) cover a group of rare tumours in Italy for which the role of occupational risk has been established. The systematic survey of NSC in the province of Brescia made it possible to analyse the jobs of the cases occurring in the area. OBJECTIVES: The aims of the research were: estimation of epithelial NSC incidence both in the general population and among wood and leather workers, description of the frequency and type of occupational exposure to substances or manufacturing processes. METHODS: The epithelial type cases were obtained from the Naso-sinusal Cancer Register (population-based) operating in the Province of Brescia since 1994. Work histories were obtained via a standardized questionnaire. RESULTS: The annual incidence ofepithelial NSC (for 100,000) in the entire population (1,090,000 inhabitants, ISTAT census 1991) from 1993 to 1997 and from 1998 to 2002 was nearly the same, 0.82 and 0.90 for men, 0.37 and 0.37 for women, respectively. The nasal cavity was the most affected anatomic site (45%) and squamous cell carcinoma was the most frequent histotype (44%) among the first 100 cases whose case histories were appropriate; in the ethmoidal sinus adenocarcinoma represented 62% of the cases; 25% of all cases were exposed to occupational carcinogens (list A) and particularly to wood dust (17%), even if only of softwood species (30%), and leather dusts (7%) especially in the shoe repair. The average latency period was 47 years (SD 7.4) and 44 years (SD 5.6) respectively; 71% of these epithelial NSC cases involved the ethmoid and 85% were adenocarcinomas. Only 1% of the cases was exposed to chromium and nickel and occurred in galvanization processes. Among the exposures to occupational risks with limited epidemiological evidence (list B) there was one case exposed to formaldehyde and 42 cases occurring in the building, agricultural, metallurgic and textile sectors. Thus all the exposures to occupational risks, both certain and probable (lists A and B) reached 84% among men and 17% among women. Epithelial NSC annual incidence rates (for 100,000) estimated among the wood and leather workers for the period 1985-2002 were 13 and 6.5 respectively. CONCLUSION: The results confirm the meaning of sentinel event for these tumours in occupational health and justify maintaining an active surveillance programme for the cases occurring in the area.

Occupational cancer in Italy.

This article is a discussion of occupational cancer in Italy. The introduction provides the necessary context of Italian industrialization and occupational health regulation. This is followed by a review of Italian epidemiologic studies of occupational cancer risks considered in terms of relative measures of risk and attributable risk of carcinogenic agents or exposure circumstances. We attempt to establish the number of workers exposed to carcinogens in Italy and the intensity of their exposures. Finally, the Italian system of compensation for occupational cancer is discussed. Several cohort and case-control studies have addressed the issue of occupational risks, mostly among male workers. The results of these studies suggest that the growing incidence of and mortality by mesothelioma is explained by the widespread and intense exposure to asbestos in some Italian industrial settings. A high attributable risk of lung tumors among male populations in industrial areas of northern Italy is explained by occupational exposures. However, insufficient data are available for clear definition of the extent and intensity of occupational exposure to carcinogenic substances. In Italy, we must prioritize and maximize resources in occupational cancer epidemiology and revitalize the role of national institutions. Recent legislation has established new regulations on the handling of carcinogenic substances in industrial settings, a new list of occupational diseases, and a national registry of mesothelioma linked to asbestos exposure. These legislative changes are expected to have positive effects.

Exposure to solvents in the shoe and leather goods industries.

The shoe and leather goods industries are two of the main economic sectors in Tuscany. Organic solvents are the most important risk factors responsible for leukaemias and polyneuropathies. Job exposure matrices for solvents have been developed with two different aims: to contribute to the general matrix in different industries involving exposure to solvents and to provide a data source for use by health professionals. The matrices have been constructed on the basis of: scientific literature, notices of chemical compositions of trade products, technical reports collected by local services, the survey of a sample of industries in the province of Florence.

Pesticide exposure assessment: a crop exposure matrix. The Working Group on Pesticide Exposure Assessment.

A crop exposure matrix (CEM) was developed in the context of two Italian case-control studies. The CEM relates agricultural practices to pesticide exposures taking into account change over time and the use of chemicals by geographical area for farming. The matrix is specific to 14 areas and to 10 major crops. The exposure axis is made up of 440 chemicals used in the last 40 years in the areas of interest. In the matrix the association between crop growing and pesticides is expressed in terms of presence or absence of exposure. Accuracy of the matrix was initially evaluated using 26 occupational histories collected within the two case-control studies. Sensitivity and specificity of CEM for some compounds were estimated versus assessment of exposure by experts. Sensitivity ranges from 83.3% to 100%, specificity from 66.2% to 95.8% depending on the chemicals.

Delayed infection, family size and malignant lymphomas.

BACKGROUND: The annual incidence of non-Hodgkin's lymphomas (NHL) is increasing by 3%-4% in different parts of the developed world. Excesses of NHL have been observed in populations exposed to immunosuppressants and to HIV, but these causes do not explain the increasing trends. It is suggested that delayed infection could explain NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. METHODS: In a population-based study on 1388 patients with NHL, 354 with Hodgkin's disease (HD) and 1718 healthy controls, the age of first occurrence of bacterial and viral diseases was investigated. Clinical records were perused in one centre to check the anamnestic data. FINDINGS: The age of occurrence of bacterial and viral diseases was significantly higher among NHL patients than in the controls. The association between later age at first bacterial or viral disease was limited to small families (OR= 1.95; 95% confidence intervals 1.26, 3.00, for age 4-8 at first infection; OR=1.91; 1.19, 3.06, for age 9+, compared with less than 4). The association was more obvious for bacterial diseases (possibly for the lower degree of misclassification). High grade lymphomas showed the strongest association. The later age of occurrence of bacterial or viral diseases in NHL patients is consistent with a higher incidence of lymphomas observed in higher social groups. No clear association was found between HD and age at first bacterial or viral diseases. INTERPRETATION: It is proposed that delayed infection could explain the increasing NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. The model of delayed infection has been proposed also to explain increasing prevalence rates of asthma.

Haematopoietic cancer and medical history: a multicentre case control study.

BACKGROUND: Viruses (such as Epstein-Barr virus) and pathological conditions (mainly involving immunosuppression) have been shown to increase the risk of haematolymphopoietic malignancies. Other associations (diabetes, tonsillectomy, autoimmune diseases) have been inconsistently reported. METHODS: The association between different haematolymphopoietic malignancies (lymphomas, myelomas and leukaemias) and the previous medical history has been studied in a population-based case-control investigation conducted in Italy, based on face to face interviews to 2669 cases and 1718 population controls (refusal rates 10% and 19%, respectively). Controls were a random sample of the general population. RESULTS: Previous findings were confirmed concerning the association between non-Hodgkin's lymphoma (NHL) and lupus erythematosus (odds ratio, OR=8.4; 95% CI 1. 6, 45), tuberculosis (OR=1.6; 1.05, 2.5) and hepatitis (1.8; 1.4, 2. 3). An association was found also between NHL and maternal (OR=2.8; 1.1, 6.9) or paternal tuberculosis (OR=1.7; 0.7, 3.9). Odds ratios of 4.0 (1.4, 11.8) and 4.4 (1.1, 6.6) were detected for the association between NHL and Hodgkin's disease, respectively, and previous infectious mononucleosis, but recall bias cannot be ruled out. No association was found with diabetes, tonsillectomy and adenoidectomy. An association with malaria at young age and "low grade" lymphatic malignancies is suggested. One interesting finding was the observation of four cases of poliomyelitis among NHL patients, one among Hodgkin's disease and one among myeloid leukaemia patients, compared with none among the controls (Fisher's exact test for NHL and Hodgkin's disease, p= 0.03, one tail). CONCLUSIONS: Some of these findings are confirmatory of previous evidence. Other observations, such as the putative role of the polio virus and of malaria are new. A unifying theory on the mechanisms by which previous medical history may increase the risk of haematolymphopoietic malignancies is still lacking.

Cytogenetic monitoring of a group of Italian floriculturists: no evidence of DNA damage related to pesticide exposure.

The induction of sister chromatid exchanges (SCE), structural chromosome aberrations (CA) or micronuclei (MN) was investigated in peripheral lymphocytes of a group of Italian floriculturists exposed to a mixture of pesticides. No statistically significant difference in the frequencies of cytogenetic damage was detected between exposed and control subjects. Assessment of the effect of confounding factors indicated that smoking affected both SCE and CA frequencies. Multiple regression analysis showed that in heavy smokers (> or = 20 cigarettes/day), SCE and CA levels increased significantly by 17% and 54%, respectively, as compared to non-smokers.

Solvents in pesticides.

Solvents are extensively used in pesticide formulations. This study concerns the solvents notified to the Italian Registry of Pesticides, which has information on approximately 8000 pesticide formulations. Solvents with evidence of carcinogenicity in humans or animals, including benzene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,4-dioxane, and 2-nitropropane, have been notified for use in pesticides. Exposure to such solvents could partly explain some of the reported excesses of leukemia and non-Hodgkin's lymphoma among farmers.

Aplastic anemia, leukemia and other cancer mortality in a cohort of shoe workers exposed to benzene.

Benzene is a well documented carcinogen for the hematic and lymphopoietic system, and experimental research confirms its carcinogenicity for tumors of other sites. This report presents the results of a historical cohort study in a shoe manufacturing plant in Florence where cases of aplastic anemia and leukemia were reported in the 1960s. A total of 1008 men and 1005 women were considered eligible members of the cohort. For total mortality, comparing the rates of the cohort with the national rates, the standardized mortality ratio (SMR) was 79 for the women and 95 for the men. For the men excesses of risk for aplastic anemia [SMR 1566; 95% confidence interval (95% CI) 547-3264] and leukemia (SMR 400, 95% CI 146-870) were observed. The increased risk occurred among workers first employed during the period in which benzene was used, but the expected number of cases in the subsequent period was too small to evaluate whether any reduction in risk had occurred. No increasing pattern with duration of employment was discernible.

[Occupational cancer in Italy]. / I tumori causati dal lavoro in Italia.

The paper is a discussion of occupational cancer in Italy. The introductory section provides the necessary context of Italian industrialization and occupational health regulation. This is followed by a review of Italian epidemiological studies of occupational cancer risks, considered in terms of relative measures of risk and Attributable Risk to carcinogenic agents or exposure circumstances. A section attempts to establish the number of workers who have been exposed to carcinogens in Italy and the intensity of their exposures. Several cohort and case-control studies have addressed the issue of occupational risks, mostly among male workers. The results of these studies suggest that the growing incidence of and mortality by mesothelioma is explained by the widespread and intense exposure to asbestos in some Italian industrial settings. A high Attributable Risk of lung tumors among male populations in industrial areas of northern Italy is explained by occupational exposures. However, insufficient data are available for the clear definition of the extent and intensity of occupational exposure to carcinogenic substances. In Italy, we need to prioritize and maximize resources in occupational cancer epidemiology and to revitalize the role of national institutions. Recent legislation has established new regulations on the handling of carcinogenic substances in industrial settings, a new list of occupational diseases, and a national registry of mesothelioma linked to asbestos exposure. These legislative changes are expected to have positive effects.

[An Italian multicenter case-control study on malignant neoplasms of the hematolymphopoietic system. Hypothesis and preliminary results on work-related risks. WILL (Working Group on Hematolymphopoietic Malignancies in Italy)]. / Studio caso-controllo multicentrico italiano sulle neoplasie maligne del sistema emolinfopoietico. Ipotesi in studio e risultati preliminari sui rischi associati alle attività lavorative. WILL. Working Group on Hematolymphopoietic Malignancies in Italy.

A multicenter case-control study was conducted in Italy in twelve areas covering a population of 7 million persons with the aim of verifying the hypothesis of an association between exposure to herbicides and to organic solvents and occurrence of lymphoma, leukaemia and multiple myeloma. 3420 cases were recruited in a three-year period (1991-1993), through periodical surveys in the main hospitals in each area. A random sample of the general population (2317 subjects) constitutes the control group. Cases and controls were face to face interviewed by trained personnel. A questionnaire was used asking about personal habits, residential and occupational history, past health status. Preliminary analyses, concerning a total of 1388 cases and 1718 controls, focused risks by occupation. Elevated risks of non Hodgkin's lymphoma (OR: 1.7; IC 95%: 0.92-3.02; based on 28 exposed cases), and of multiple myeloma (OR: 3.6; IC 95%: 1.51-8.63; based on 9 exposed cases) were shown for welders. Among female hairdressers there were elevated risks of non Hodgkin's lymphoma (OR: 1.8; IC 95%: 0.76-4.30; based on 8 exposed cases), multiple myeloma (OR: 3.3; IC 95%: 0.77-14.15; based on 3 exposed cases) and Hodgkin's disease (OR: 2.0; IC 95%: 0.93-4.47; based on 16 exposed cases).

Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study.

BACKGROUND: Few studies have analysed the association between alcohol intake and Hodgkin's lymphoma (HL) or multiple myeloma (MM) risks. MATERIALS AND METHODS: A multicentre population-based case-control study of 363 HL, 270 MM cases, and 1771 controls offered the opportunity to evaluate the relationship between alcohol and HL/MM risks. Unconditional logistic regression was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs), associated with alcohol intake (servings per week, grams per day of ethanol intake) or duration of exposure (year). RESULTS: For HL, considering nonsmokers only, ever drinkers had a significantly decreased risk than never drinkers (OR=0.46). Significantly lower risks in all levels of total alcohol intake were also detected, considering servings per week (OR for one to four servings per week=0.51, 95% CI 0.32-0.82; OR for five to nine servings per week=0.39, 95% CI 0.21-0.73; OR for 10-19 servings per week=0.26, 95% CI 0.12-0.54; OR for >or=20 servings per week=0.34, 95% CI 0.15-0.79) and grams per day of ethanol intake (OR for 0.1-9.0 g/day=0.45, 95% CI 0.27-0.74; OR for 9.1-17.9 g/day=0.52, 95% CI 0.30-0.90; OR for 18.0-31.7 g/day=0.27, 95% CI 0.13-0.57; OR for >31.7 g/day=0.35, 95% CI 0.15-0.79). In the analysis for ever-smoking HL cases and controls, ever drinkers had the same risk as never drinkers. For MM, ever drinkers had a non-significantly decreased risk than non-drinkers (OR=0.74), and ORs in almost all consumption levels were not significant (OR for 0.1-9.0 g/day=0.93; OR for 9.1-17.9 g/day=0.82; OR for 18.0-31.7 g/day=0.47; 95% CI 0.28-0.81; OR for >31.7 g/day=0.68). For HL and MM, the beverage type did not affect the risk significantly, and no consistent dose-response relationships were found, considering intensity or duration of alcohol consumption. CONCLUSIONS: Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases.

Cigarette smoking and alcohol consumption as determinants of survival in non-Hodgkin's lymphoma: a population-based study.

BACKGROUND: The risk of non-Hodgkin's lymphoma (NHL) seems to be enhanced by cigarette smoking and lowered by alcohol drinking. PATIENTS AND METHODS: To assess whether cigarette smoking and alcohol drinking affect NHL survival, a population-based prospective study on 1138 Italian patients, diagnosed in 1991-1993, followed-up until 2002, was carried out. At diagnosis, clinical and socio-demographic data were recorded and lifestyle habits were assessed through a validated questionnaire. Survival analysis was performed with Kaplan-Meier methods. Hazard ratios (HR) were estimated by Cox regression. RESULTS: The mean follow-up was 6.6 years (standard deviation (SD) 4.3). The mean survival time was 7.56 years (SD 0.155). At both univariate and multivariate analysis heavy cigarette smoking and alcohol drinking were associated with poor survival. Compared with those with a lower cumulative exposure to tobacco smoking, those who had smoked>31 pack-years had a worse survival (HR=1.60, 95%CI=1.18-2.18). Drinkers had a higher risk of death compared with non-drinkers (HR=1.41, 95%CI=1.10-1.81). Considering only those who had NHL as cause of death, the HR for the higher category of pack-years smoked, compared with the lowest, was 1.63 (95% CI=1.15-2.33) and for drinkers, compared with non-drinkers, it was 1.33 (95% CI=1.01-1.80). CONCLUSIONS: cigarette smoking and alcohol drinking may influence NHL survival.

Health and work among women in Italy: an overview of the epidemiological literature.

The objective of this paper is to give an overview of the epidemiological studies completed in Italy during the past 25 years, about the role of occupational exposures on the development of adverse health effects on women. The implications for research developments are also discussed. The epidemiological investigations of selected categories of work-related health effects published in Italy in the years 1970-1995 were identified from the medical literature databases. The total number of studies is 142, including cohort mortality studies (n = 12), case-control studies of different neoplasms (n = 14), investigations of adverse reproductive effects (n = 8) and studies of occupational diseases different from the above (n = 94). In most investigations, women workers were not the main study objective and hence the number of females under study was small. The conclusions is that in Italy, given the dearth of studies of female workers and the preponderance of women in many economic sectors, i.e. the textile and shoe industry, health care, personal services and schools, there is a need to identify women workers in the above industries and occupations as priorities for epidemiological research and surveillance.