SETIL: Italian multicentric epidemiological case-control study on risk factors for childhood leukaemia, non hodgkin lymphoma and neuroblastoma: study population and prevalence of risk factors in Italy.

BACKGROUND: Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case-control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. METHODS: The study was carried out in 14 Italian regions (78.3% of Italian population aged 0-10). It included leukaemia, NHL and neuroblastoma cases incident in 0-10 year olds in 1998-2001, registered by the Italian Association of Paediatric Haematology and Oncology (AIEOP) (accrual over 95% of estimated incidence). Two controls for each leukaemia case were randomly sampled from the Local Health Authorities rolls, matched by gender, birthdate and residence. The same controls were used in NHL and neuroblastoma studies. Parents were interviewed at home on: physical agents (ELF-MF and ionizing radiation), chemicals (smoking, solvents, traffic, insecticides), occupation, medical and personal history of children and parents, infectious diseases, immunizations and associated factors. Occupational exposure was collected using job specific modules. ELF-MF was measured in the main rooms (spot measurement) and close to child's bed (48 hours measurement). RESULTS: The study included: 683 leukaemia cases (87% ALL, 13% AnLL), 97 NHL, 155 neuroblastomas, and 1044 controls. CONCLUSIONS: SETIL represents a data source on exposure of Italian children to a broad array of potential carcinogenic factors.

Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

BACKGROUND: Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. METHODS: Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. RESULTS: Paternal smoke in the conception period was associated with AnLL (OR for ≥ 11 cigarettes/day  = 1.79, 95% CI 1.01-3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97-3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. CONCLUSIONS: This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

Risk of neuroblastoma, maternal characteristics and perinatal exposures: the SETIL study.

PURPOSE: Neuroblastoma (NB) is the most common extra-cranial paediatric solid tumour. Incidence peaks in infancy, suggesting a role of in-utero and neonatal exposures but its aetiology is largely unknown. The aim of the present study is to evaluate the association between maternal characteristics and perinatal factors with the risk of NB, using data from the SETIL database. METHODS: SETIL is a large Italian population-based case-control study established to evaluate several potential cancer risk factors in 0-10 year olds. Information about maternal characteristics, reproductive history, environmental and occupational exposures during pregnancy, as well as newborns' characteristics were obtained using a structured questionnaire. Extremely low frequency magnetic field (ELF-MF) home exposure was measured. The study included 1044 healthy controls and 153 NB cases, diagnosed between 1998 and 2001. RESULTS: A twofold risk was associated to exposure in pregnancy to chemical products for domestic work and to hair dye. The risk associated with the latter was higher among 0-17 month old children (OR = 5.5, 95%CI: 1.0-29.3). Risk was increased for children whose mothers had suffered work related exposure in the preconception period to solvents (OR = 2.0 95%CI: 1.0-4.1) and in particular to aromatic hydrocarbons (OR = 9.2, 95%CI: 2.4-34.3). No association was observed with ELF-MF exposure. A higher risk was found among children with congenital malformations (OR = 4.9, 95%CI: 1.8-13.6) or neurofibromatosis (2 cases and 0 controls, p = 0.016). CONCLUSIONS: Our study suggests maternal exposure to hair dyes and aromatic hydrocarbons plays a role and deserves further investigation. The association with congenital malformations might also be explained by over-diagnosis. External exposure, in particular during and before pregnancy might contribute to NB occurrence.

Tobacco smoke and risk of childhood acute lymphoblastic leukemia: findings from the SETIL case-control study.

PURPOSE: Tobacco smoke could cause childhood acute lymphoblastic leukemia (ALL) through at least three pathways: (1) prenatal parental smoking; (2) fetal exposure through maternal smoking during pregnancy; and (3) childhood exposure to secondhand smoke (SHS). We tested these hypotheses in a large population-based case-control study (SETIL) primarily designed to evaluate the role of electromagnetic fields in childhood hematopoietic malignancies. METHODS: From 1998 to 2003, we enrolled 602 incident cases of ALL from 14 Italian Regions, and 918 controls were individually matched by birthdate, sex, and area of residence. Cases (n = 557) and controls (n = 855) with complete information were analyzed; odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated with logistic regression models conditioned on matching variables and adjusted by birth order, birthweight, duration of breastfeeding, parental age at delivery, education, and occupational exposure to benzene. RESULTS: No evidence associating paternal smoking in the conception period or maternal smoking during the pregnancy with ALL was found. An association of ALL with maternal exposure to SHS during pregnancy (adjusted OR for mothers exposed more than 4 h/day = 2.18, 95 % CI 1.39-3.42) was observed, but recall bias cannot be excluded. Exposure of the children to SHS was associated with ALL only in unadjusted analysis (unadjusted OR for highly exposed children = 1.64; 95 % CI 1.10-2.45). CONCLUSIONS: This study does not support the hypothesis that parental active smoking is associated with ALL. We found very weak evidence of increased risk of ALL for children exposed to SHS. Maternal exposure to SHS was associated with ALL, but recall bias is likely to inflate our estimates.

Risk of childhood leukaemia and non-Hodgkin's lymphoma after parental occupational exposure to solvents and other agents: the SETIL Study.

AIM: In the context of the Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma (SETIL), the risk of childhood cancer was investigated in relation to parental occupational exposures. METHODS: All cases of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in children aged 0-10 years were identified. Controls were chosen at random from the local population in each region. Parents were interviewed using a structured questionnaire. The collected data were blindly reviewed by expert industrial hygienists in order to estimate exposure to a list of agents. Statistical analyses were performed for each agent using unconditional multivariable logistic regression models, taking into account timing of exposure. RESULTS: 683 cases of acute childhood leukaemia, 97 cases of NHL and 1044 controls were identified. Increased risk of childhood leukaemia was found for maternal exposure to aliphatic (OR 4.3) or aromatic hydrocarbons (OR 3.8) in the preconception period, and for paternal exposure to diesel exhaust (OR 1.4), lead exposure (OR 1.7) and mineral oils (OR 1.4)[corrected]. Risk of NHL appeared to be related to paternal exposure to oxygenated solvents (OR 2.5) and petrol exhaust (OR 2.2). CONCLUSIONS: We found increased risk for childhood leukaemia associated with maternal occupational exposure to aromatic and aliphatic hydrocarbons, particularly in the preconception period; increased risks were also observed for paternal exposure to diesel exhaust fumes, mineral oils and lead. The risk of NHL appeared to be related to paternal exposure to oxygenated solvent and petrol exhausts.

[Solar ultraviolet radiation risk in outdoor workers: a specific project of Tuscany Region (Italy)]. / Rischio da radiazione solare ultravioletta nei lavoratori outdoor: piano mirato della Regione Toscana.

OBJECTIVE: The aims of Tuscany Regional project were: to study the sun protection attitude of outdoor workers; to measure solar ultraviolet (UV) exposure in work environment; to describe the frequency of photoaging, precancerous lesions, and skin cancers in outdoor workers; to collect information on solar ultraviolet radiation exposure from incident cases of Non-Melanoma Skin Cancer (NMSC) recruited from Tuscany Cancer Registry. DESIGN: Outdoor workers completed a questionnaire devoted to collect information on sun protection attitudes during a typical summer working week. Environmental and personal measurements were carried out. Expert dermatologists examined outdoor workers to assess the frequency of photoaging, precancerous lesions, and skin cancer. A structured questionnaire was mailed to incident cases of NMSC. Information were collected on personal habits and working history, focusing on solar ultraviolet radiation exposure. SETTING AND PARTICIPANTS: Agriculture, construction, quarrying and fishing activities were considered: 292 employees responded to questions about the type of clothing used in the morning and in the afternoon,while working outdoors; 637 outdoor workers underwent skin examination. We contacted 743 cases of NMSC occurred in 2004; 498 subjects accepted to participate in this study. RESULTS: The clothing worn by surveyed subjects was often inadequate compared to the high level of exposure to UV. The skin examination of 637 outdoor workers highlighted 2 melanomas, 7 epitheliomas and 35 actinic keratoses. Among the 498 cases of NMSC, 135 (27%) were diagnosed in outdoor workers. Most represented economic activity sectors were: agriculture, construction, transport, sports. CONCLUSION: The characterization of outside workers revealed unsatisfactory sun protection behaviours. Moreover, previously undetected skin cancers were diagnosed. The study on MNSC confirms the complexity of studying the exposure to UV radiation. The Tuscany Regional project provided useful information on the risk of solar ultraviolet radiation in outdoor workers. Prevention programs are needed.

[PAH exposure in asphalt workers]. / Monitoraggio biologico dell'esposizione ad idrocarburi policiclici aromatici in un gruppo di asfaltatori.

BACKGROUND: There has been interest in evaluating the potential carcinogenicity of bitumen fumes in asphalt workers since the 1960's. The IARC classified air-refined bitumens as possible human carcinogens, while coal-tar fumes were classified as known carcinogens. Occupational/environmental PAH exposure can be measured by several urinary markers. Urinary 1-OHP has become the most commonly used biological marker of PAH exposure in asphalt workers. OBJECTIVES: The aim of this study was to assess asphalt workers' exposure levels by monitoring 1-OHP urinary excretion and compare this data with those of non-occupationally exposed subjects. METHODS: We investigated three groups of asphalt workers: 100 in summer 2007, 29 in winter 2007, and 148 during summer 2008 and compared 1-OHP urinary concentrations using Kruskall-Wallis test. RESULTS: Median 1-OHP urinary concentrations during the three biomonitoring sampling periods were 0.65, 0.17 and 0.53 microg/g creatinine respectively. There was a significant difference in 1-OHP values between the three groups (p < 0.001). CONCLUSIONS: our study showed that PAH exposure of asphalt workers' is higher than that observed in the general population and in workers in urban areas. Our results suggest that PAH exposure in the three groups studied is not sufficiently kept under control by the use of personal protective equipment and that biomonitoring is useful in evaluating PAH exposure and for risk assessment. Regulations need to be enforced for workers exposed to cancer risk, such as the register of workers exposed to carcinogens.

[Work-related carpal tunnel syndrome. Motivations and results of a surveillance system]. / Sindrome del tunnel carpale da attività lavorativa. Motivazioni e risultati di un sistema di sorveglianza.

BACKGROUND: Current statistics show that work-related carpal tunnel syndrome (CTS) has been increasing constantly over the last ten years. Nevertheless, available data on the incidence of CTS in the general population and on the occupational proportion of the aetiology of this disease suggest considerable underreporting of work-related cases, which reflects on the number of cases reported to INAIL (National Insurance Institute for Industrial Accidents) and does not give an accurate epidemiological picture of their origin and distribution. For this reason, in the course of a prevention programme of upper limb disorders due to biomechanical overload, a second experiment concerning CTS surveillance system was carried out by collecting self-reported information via postal questionnaires. The aim of this study was to estimate the prevalence of work-related cases in the selected group of the general population and to identify work tasks and factories with significant risk of CTS clusters. METHODS: From the hospital discharge lists of the Province of Brescia for 2001 and 2005, 1558 surgical cases were selected, aged 18-65 years, excluding housewives (nearly 25% of the total); thus 637 surgical cases were included in the study (68.6% female and 31.4% male). RESULTS AND CONCLUSIONS: Obesity frequency was observed to be higher in the sample than in the general population. This was not the case for diabetes. The probability of surgical CTS cases attributable to occupational exposure was estimated by dividing the 637 cases into three exposure categories:probable, possible and improbable with results of respectively 44.4%, 36.6% and 19%; in the first category, the frequency among females was 78.8%. The CTS cases among females less than 40 years old was 40% in the probable exposure category versus 10% into the improbable exposure category. In the latter category, the prevalence of concomitant hand tendinitis was 11% versus 22% in the probable exposure category. Obese patients fell into the three occupational risk groups in the same proportion. Among the 283 STC cases considered as probable occupational exposure cases, only 11 were reported as required by law to the Occupational Health Service. Whereas a number of work tasks and work sectors with high risk factors were confirmed, there were relatively few factories with a possible presence of clusters, probably due to the small sample size compared to the general population and to the density of the factories potentially at risk. The epidemiological surveillance thus carried out provided more evidence confirming the serious underreporting of the work-related STC cases in a highly industrialised province and also provided useful information on the local situation regarding high-risk occupations, which need to be addressed via interventions of primary prevention should, possibly with greater involvement of the occupational physicians.

Evaluation of inhaled and cutaneous doses of imidacloprid during stapling ornamental plants in tunnels or greenhouses.

The aim of this research was to assess dermal and respiratory exposure of workers to imidacloprid during manual operations with ornamental plants previously treated in greenhouses or tunnels. A total of 10 female workers, 5 in greenhouses and 5 in tunnels, were monitored for 3 or 5 consecutive days. Actual skin contamination, excluding hands, was evaluated using nine filter paper pads placed directly on the skin. To evaluate the efficacy of protective clothing in reducing occupational exposure we also placed four pads on top of the outer clothing. Hand contamination was evaluated by washing with 95% ethanol. Respiratory exposure was evaluated by personal air sampling. Respiratory dose was calculated on the basis of a lung ventilation of 15 l/min. Absorbed doses were calculated assuming a skin penetration of 10% and a respiratory retention of 100%. Dislodgeable foliar residues (DFRs) were determined during the days of re-entry in order to determine the dermal transfer factor. From the dependence of dermal exposure of hands from DFRs, a mean transfer factor was estimated to be 36.4 cm(2)/h. Imidacloprid was determined by liquid chromatography with selective mass detection and electrospray interface in all matrices analysed. Respiratory dose was 4.1+/-4.0 (0.1-14.3)% and 3.0+/-2.0 (0.6-6.9)% (mean+/-SD (range)) of the total real dose during work in tunnels and greenhouses, respectively. The estimated absorbed doses, 0.29+/-0.45 microg/kg (0.06-2.25 microg/kg) body weight and 0.32+/-0.18 microg/kg (0.07-0.66 microg/kg) body weight (mean+/-SD (range)) in tunnels and in greenhouses, respectively, were less than the acceptable operator exposure level of 0.15 mg/kg body weight and than the acceptable daily intake of 0.05 mg/kg body weight. The hands and exposed skin of all workers were found to be contaminated, indicating that greater precautions, such as daily changing of gloves and clothing, are necessary to reduce skin exposure.

Risk of leukemia and multiple myeloma associated with exposure to benzene and other organic solvents: evidence from the Italian Multicenter Case-control study.

BACKGROUND: While there is a general consensus about the ability of benzene to induce acute myeloid leukemia (AML), its effects on chronic lymphoid leukemia and multiple myeloma (MM) are still under debate. We conducted a population-based case-control study to evaluate the association between exposure to organic solvents and risk of myeloid and lymphoid leukemia and MM. METHODS: Five hundred eighty-six cases of leukemia (and 1,278 population controls), 263 cases of MM (and 1,100 population controls) were collected. Experts assessed exposure at individual level to a range of chemicals. RESULTS: We found no association between exposure to any solvent and AML. There were elevated point estimates for the associations between medium/high benzene exposure and chronic lymphatic leukemia (OR = 1.8, 95% CI = 0.9-3.9) and MM (OR = 1.9, 95% CI = 0.9-3.9). Risks of chronic lymphatic leukemia were somewhat elevated, albeit with wide confidence intervals, from medium/high exposure to xylene and toluene as well. CONCLUSIONS: We did not confirm the known association between benzene and AML, though this is likely explained by the strict regulation of benzene in Italy nearly three decades prior to study initiation. Our results support the association between benzene, xylene, and toluene and chronic lymphatic leukemia and between benzene and MM with longer latencies than have been observed for AML in other studies.

Cancer and pesticides: an overview and some results of the Italian multicenter case-control study on hematolymphopoietic malignancies.

Exposure to pesticides is recognized as an important environmental risk factor associated with development of cancer. Epidemiological studies, although sometimes contradictory, have linked phenoxy acid herbicides with non-Hodgkin's lymphoma (NHL) and Soft Tissue Sarcoma (STS); organochlorine insecticides with STS, NHL, and leukemia; organophosphorous compounds with NHL and leukemia; and triazine herbicides with ovarian cancer. Exposure assessment is a crucial point in studying the association between cancer and pesticides. In order to investigate the association between hematolymphopoietic malignancies and occupational exposures, including pesticides, a population-based case-control study was carried out in Italy in 11 areas, 9 of which are agricultural or mixed areas. All newly diagnosed cases of hematolymphopoietic malignancies were collected in a 3-year period (1991-1993). The control group consisted of a random sample of the population residing in each area. The approach to infer exposures in agriculture was based on: the use of an agricultural questionnaire with 24 crop-specific questionnaires; expert agronomists who reviewed the collected information for each subject and translated it into pesticides histories. In total, 1925 cases and 1232 controls were interviewed in the nine agricultural areas. Increased risk was observed for some specific classes of pesticides. Furthermore, a nonstatistically significant increased risk of NHL was observed for subjects who were exposed to phenoxy herbicides not using protective equipment and a significant increased risk for exposure to 2, 4-dichlorophenoxy acetic acid (2,4-D).

Occupational exposure to solvents and the risk of lymphomas.

BACKGROUND: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case-control study in Italy. METHODS: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991-1993 were identified in 8 areas in Italy. The control group was formed by a random sample of the general population in the areas under study stratified by sex and 5-year age groups. We interviewed 1428 non-Hodgkin lymphoma cases, 304 Hodgkin disease cases, and 1530 controls. Experts examined the questionnaire data and assessed a level of probability and intensity of exposure to a range of chemicals. RESULTS: Those in the medium/high level of exposure had an increased risk of non-Hodgkin lymphoma with exposure to toluene (odds ratio = 1.8; 95% confidence interval = 1.1-2.8), xylene 1.7 (1.0-2.6), and benzene 1.6 (1.0-2.4). Subjects exposed to all 3 aromatic hydrocarbons (benzene, toluene, and xylene; medium/high intensity compared with none) had an odds ratio of 2.1 (1.1-4.3). We observed an increased risk for Hodgkin disease for those exposed to technical solvents (2.7; 1.2-6.5) and aliphatic solvents (2.7; 1.2-5.7). CONCLUSION: This study suggests that aromatic and chlorinated hydrocarbons are a risk factor for non-Hodgkin lymphomas, and provides preliminary evidence for an association between solvents and Hodgkin disease.

Prognostic significance of p53 and Ki-67 antigen expression in surgically treated non-small cell lung cancer: immunocytochemical detection with imprint cytology.

The purpose of this study was to determine the prognostic significance of the expression of p53 and Ki-67 in non-small cell lung cancer (NSCLC) using immunocytochemical detection. All consecutive NSCLC cases were selected for study, and, after surgery, a part of each tumor sample was frozen at -20 degrees C and stored for immunocytochemical studies. Overexpression of p53 was associated significantly with worse patient outcome in stage I disease, whereas no excess risk was evident in stage II and III cases. The same pattern was observed for Ki-67 expression. The excess risk in stage I cases with p53 and Ki-67 overexpression was observed only in adenocarcinoma. These findings are in agreement with other retrospective studies and support the hypothesis that p53 alteration may have different roles in adenocarcinoma and in squamous cell carcinoma, such as a carcinogenic factor for both cellular types but progression only for adenocarcinoma.

Personal use of hair dyes and hematolymphopoietic malignancies.

In the context of a population-based case-control study in Italy, the authors investigated the possible association between the personal use of hair dyes and non-Hodgkin's lymphoma (NHL), leukemia, multiple myeloma, and Hodgkin's disease. They collected all incident cases of hematolymphopoietic malignancies; the control group was formed with a random sample of the general population. Overall, the authors interviewed 2,737 research subjects and 1,779 control subjects. Among women, the authors found no association between ever using hair dyes and the risk of hematolymphopoietic malignancies. However, for permanent hair dyes, the authors observed a slightly increased risk of lymphocytic leukemia (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 0.8-2.2) and of follicular subtypes of NHL (OR= 1.3; 95% CI = 0.8-2.0). Women who used black hair dye colors were at an increased risk of developing leukemia (OR = 1.9; 95% CI = 1.0-3.4), in particular chronic lymphocytic leukemia (OR = 3.0; 95% CI = 1.1-7.5). In spite of the lack of information on the timing and frequency of hair dye use and the imprecision of the ORs, associations were suggested between leukemia and permanent black hair dye use and follicular NHL and the use of permanent hair dyes.

Non-Hodgkin's lymphoma, leukemia, and exposures in agriculture: results from the Italian multicenter case-control study.

BACKGROUND: The etiology of non-Hodgkin's lymphoma (NHL) and leukemia is still largely unknown, but exposure to chemicals, in particular pesticides, has been suggested to be a risk factor. METHODS: A large population-based case-control study was conducted in Italy with the aim of investigating the associations between pesticide exposure and NHL, and solvents and leukemia. Data presented in this article refer to 1,575 interviewed cases and 1,232 controls in the nine agricultural study areas. RESULTS: Exposure to nitro-derivatives and phenylimides among fungicides, hydrocarbon derivatives and insecticide oils among insecticides, and the herbicide amides are the chemical classes observed to be associated with the pathologies under investigation. CONCLUSIONS: The results of the case-control study suggest an increased risk for NHL and leukemia, and some chemical classes of pesticides, although few are statistically significant and some are based on few exposed cases. The results also show that men and women experience both similar and different risks for the same environmental agricultural exposures. Am. J. Ind. Med. 44:627-636, 2003.