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Castel Guelfo di Bologna, Italy

Miligi L.,ISPO Cancer Prevention and Research Institute | Benvenuti A.,ISPO Cancer Prevention and Research Institute | Mattioli S.,University of Bologna | Salvan A.,CNR Institute for System Analysis and Computer Science Antonio Ruberti | And 19 more authors.
Occupational and Environmental Medicine | Year: 2013

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 1.4) and mineral oils (OR 1.7). 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.

Faaij C.M.J.M.,Leiden University | Willemze A.J.,Leiden University | Revesz T.,Womens and Childrens Hospital | Balzarolo M.,Leiden University | And 12 more authors.
Pediatric Blood and Cancer | Year: 2010

Chemokine receptor/ligand interactions orchestrate the migration of cells to peripheral tissues such as the skin. We analysed chemokine receptor expression by acute myeloid leukaemic (AML) cells present in peripheral blood (n=7), bone marrow (n=6), or skin (n=11) obtained from 15 paediatric AML patients with skin involvement and in 10 AML patients without skin involvement. High percentages of circulating CCR2pos AML cells were only detected in patients with extramedullary disease. Skin-residing AML cells displayed a different set of receptors in situ, namely: CCR5, CXCR4, CXCR7 and CX3CR1. These results suggest the involvement of different chemokine/chemokine receptor interactions in homing and retention of AML blasts in the skin. © 2010 Wiley-Liss, Inc.

Parodi S.,National Research Council Italy | Merlo D.F.,Epidemiology | Ranucci A.,University of Piemonte Orientale | Miligi L.,ISPO Cancer Prevention and Research Institute | And 44 more authors.
Cancer Epidemiology | Year: 2014

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. © 2014 Elsevier Ltd.

Bachas C.,VU University Amsterdam | Schuurhuis G.J.,VU University Amsterdam | Reinhardt D.,Hannover Medical School | Creutzig U.,Hannover Medical School | And 11 more authors.
British Journal of Haematology | Year: 2014

Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n = 198) of relapsed non-French-American-British M3, non-Down syndrome AML patients that received similar relapse treatment. We correlated molecular aberrations with clinical and biological factors and studied their prognostic relevance. Hotspot mutations in the analysed genes were detected in 92 out of 198 patients (46·5%). In 72 of these 92 patients (78%), molecular aberrations were mutually exclusive for the currently analysed genes. FLT3-internal tandem repeat (ITD) (18% of total group) mutations were most frequent, followed by NRAS (10·2%), KRAS (8%), WT1 (8%), KIT (8%), NPM1 (5%) and FLT3-tyrosine kinase domain (3%) mutations. Presence of a WT1 aberration was an independent risk factor for second relapse (Hazard Ratio [HR] = 2·74, P = 0·013). In patients who achieved second complete remission (70·2%), WT1 and FLT3-ITD aberrations were independent risk factors for poor overall survival (HR = 2·32, P = 0·038 and HR = 1·89, P = 0·045 respectively). These data show that molecular aberrations at first relapse are of prognostic relevance and potentially useful for risk group stratification of paediatric relapsed AML and for identification of patients eligible for personalized treatment. © 2014 John Wiley & Sons Ltd.

Balgobind B.V.,Paediatric Oncology Haematology | Hollink I.H.I.M.,Paediatric Oncology Haematology | Reinhardt D.,AML BFM Study Group | van Wering E.R.,DCOG | And 9 more authors.
European Journal of Cancer | Year: 2010

Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies in paediatric AML are scarce, and reported large differences in the frequency of MLL-PTD, frequently utilising mRNA RT-PCR only to detect MLL-PTDs. We studied the frequency of MLL-PTD in a large cohort of paediatric AML (n = 276) and the results from two different methods, i.e. mRNA RT-PCR, and multiplex ligation-dependent probe amplification (MLPA), a method designed to detect copy number differences of specific DNA sequences. In some patients with an MLL-rearrangement, MLL-PTD transcripts were detected, but were not confirmed by DNA-MLPA, indicating that DNA-MLPA can more accurately detect MLL-PTD compared to mRNA RT-PCR. In paediatric AML, MLL-PTD was detected in 7/276 patients (2.5%). One case had a trisomy 11, while the others had normal cytogenetics. Furthermore 4 of the 7 patients revealed a FLT3-ITD, which was significantly higher compared with the other AML cases (p = 0.016). In conclusion, using DNA-MLPA as a novel screenings technique in combination with mRNA RT-PCR a low frequency of MLL-PTD in paediatric AML was found. Larger prospective studies are needed to further define the prognostic relevance of MLL-PTD in paediatric AML. © 2010 Elsevier Ltd. All rights reserved.

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