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

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Abstract

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.

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Acknowledgments

The SETIL study was financially supported by research grants received by AIRC (Italian Association on Research on Cancer), MIUR (Ministry for Instruction, University and Research, PRIN Program), Ministry of Health (Ricerca Sanitaria Finalizzata Program), Ministry of Labour and Welfare, Associazione Neuroblastoma, Piemonte Region (Ricerca Sanitaria Finalizzata Regione Piemonte Program), Liguria Region, Comitato per la vita “Daniele Chianelli”-Associazione per la Ricerca e la Cura delle Leucemie, Linfomi e Tumori di Adulti e Bambini (Perugia). Andrea Farioli’s work on this paper was supported by the Master in Epidemiology, University of Turin. We would like to acknowledge the contributors to the design and conduct of the SETIL study: Antonio Acquaviva, AOU di Siena, Siena, Italia; Daniele Andreuccetti, I.R.O.E.—CNR—Firenze, Italia; Laura Anglesio, ARPA—Ivrea (To), Italia; Maurizio Aricò, AOU Meyer, Firenze, Italia; Giorgio Assennato, ARPA—Puglia, Bari, Italia; Francesco Barone Adesi, CPO Piemonte, Torino, Italia; Isabella Belletti, National Cancer Institute, Milano, Italia; Gabriella Bernini, AOU Meyer, Firenze, Italia; Marinella Bertolotti, CPO Piemonte, Torino, Italia; Paolo Bevitori, ARPA Rimini, Rimini, Italia; Renzo Biancotto, ARPAV—Venezia, Italia; Pierfranco Biddau, Ospedale Microcitemico, Cagliari, Italia; Annibale Biggeri, Università degli Studi di Firenze, Firenze, Italia; Luigi Bisanti, ASL di Milano, Milano, Italia; Vittorio Bocchini, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italia; Francesco Bochicchio, Istituto Superiore di Sanità, Roma, Italia; Silvia Bucci, ARPAT, Firenze, Italia; Roberto Calisti, SPreSAL, Civitanova Marche, Italia; Santina Cannizzaro, Lega Italiana per la Lotta contro i Tumori Onlus, Ragusa, Italia; Nicola Caranci, Agenzia sanitaria e sociale regionale, Emilia-Romagna, Bologna, Italia; Veronica Casotto, IRCCS Burlo Garofolo, Trieste, Italia; Fulvio Cavariani, Centro Regionale Amianto, Viterbo, Italia; Egidio Celentano, ARSAN—Agenzia Regionale Sanitaria della Campania, Napoli, Italia; Manuela Chiavarini, Università degli Studi di Perugia, Perugia, Italia; Pierluigi Cocco, Università di Cagliari, Cagliari, Italia; Pietro Comba, Istituto Superiore di Sanità, Roma, Italia; Paolo Crosignani, Istituto Nazionale Tumori, Milano, Italia; Marina Cuttini, Ospedale Pediatrico Bambino Gesù, Roma, Italia; Giovanni d’Amore, ARPA, Ivrea (To), Italia; Gigliola de Nichilo, SPESAL, Barletta, Italia; Gian Luca De Salvo, Istituto Oncologico Veneto IRCCS, Padova, Italia; Elena Duglio, IRCCS AOU San Martino-ITS, IST Genova, Italia; Myris Erna, PMP Fisica, Padova, Italia; Daniela Ferrante, CPO Piemonte, Novara, Italia; Francesco Forastiere, Dipartimento Epidemiologia Regione Lazio, Roma, Italia; Lorenzo Gafà, Lega Italiana per la Lotta contro i Tumori Onlus, Ragusa, Italia; Claudia Galassi, AOU S.Giovanni Battista e CPO Piemonte, Torino, Italia; Luigi Gelli, Struttura Regionale dell’Autorità Ambientale, Regione Campania, Napoli, Italia; Marco Gilardetti, CPO Piemonte, Torino, Italia; Erni Guarino, Istituto Nazionale Tumori, Napoli, Italia; Paolo Guidotti, ITI, Firenze, Italia; Riccardo Haupt, Istituto Giannina Gaslini, Genova, Italia; Ursula Kirchmayer, Dipartimento Epidemiologia Regione Lazio, Roma, Italia; Susanna Lagorio, National Institute of Health, Rome, Italia; Alma Lippi, AOU Meyer, Firenze, Italia; Franco Locatelli, Università di Pavia, Pavia, Italia; Mirti Lombardi, PMP, Ancona, Italia; Dana Loomis, University of North Carolina—USA; Lia Lidia Luzzatto, ASL 1—Torino, Torino, Italia; Mauro Magnoni, ARPA—Ivrea (To), Italia; Giuseppe Masera, Università Milano Bicocca, Monza, Italia; Pia Massaglia, Neuropsichiatria Infantile, Torino, Italia; Franco Merletti, Università di Torino, Torino, Italia; Domenico Franco Merlo, IRCCS Azienda Ospedaliera Universitaria San Martino- IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italia; Giuseppe Miceli, Azienda Sanitaria Locale.7, Ragusa, Italia; Paola Michelozzi, Dipartimento Epidemiologia Regione Lazio, Roma, Italia; Liliana Minelli, Università degli Studi di Perugia, Perugia, Italia; Daniele Monetti, Istituto Oncologico Veneto IRCCS, Padova, Italia; Paola Mosciatti, Università di Camerino, Camerino, Italia; Alessandra Greco, Istituto Oncologico Veneto IRCCS, Padova, Italia; Piero Mozzo, Centro Radioattività Ambientale, Verona, Italia; Margherita Nardi, AOU di Pisa, Pisa, Italia; Cristina Nuccetelli, Istituto Superiore di Sanità, Roma, Italia; Salvatore Panico, Università degli Studi di Napoli, Napoli, Italia; Franco Pannelli, Registro Tumori di Macerata e Università di Camerino, Camerino, Italia; Guido Paolucci, University of Bologna, Bologna, Italia; Andrea Pession, University of Bologna, Bologna, Italia; Alessandro Polichetti, National Institute of Health, Roma, Italia; Andrea Poggi, ARPAT, Firenze, Italia; Vincenzo Poggi, A.O.R.N. Santobono—Pausilipon, Napoli, Italia; Ombretta Pons, Dip. Scienze Biomediche, Torino, Italia; Alessandro Pulsoni, La Sapienza, Università di Roma, Roma, Italia; Assunta Rasulo, CPO Piemonte, Torino, Italia; Serena Risica, Istituto Superiore di Sanità, Roma, Italia; Carmelo Rizzari, A.O. San Gerardo, Fondazione MBBM, Monza, Italia; Stefano Roletti, ARPA, Ivrea (To), Italia; Maria Rosa, Sez.Fisica Ambientale, Mestre (Ve), Italia; Ornella Ru, CPO Piemonte, Torino, Italia; Giovanna Russo, Università di Catania, Catania, Italia; Giuseppe Sampietro, ASL Città di Milano, Milano, Italia; Gino Schilirò, Università di Catania, Catania, Italia; Giuseppe Sgorbati, PMP, Milano, Italia; Stefano Silvestri, ISPO, Firenze, Italia; Lorenzo Simonato, Università degli Studi di Padova, Padova, Italia; Donato Sivo, Università di Bari, Bari, Italia; Letizia Sommani, ASF Firenze, Firenze, Italia; Bianca Stievano, Sez.Fisica Ambientale, Padova, Italia; Benedetto Terracini, Dip. Scienze Biomediche, Torino, Italia; Santi Tofani, ASL Ivrea, Ivrea, Italia; Maria Valeria Torregrossa, Università degli Studi di Palermo; Palermo, Italia; Loredana Troeschel, National Cancer Institute, Milano, Italia; Flavio Troti, Centro Radioattività Ambientale, Verona, Italia; Rosario Tumino, Registro Tumori di Ragusa, Ragusa, Italia; Rosaria Maria Valenti, Università degli Studi di Palermo, Palermo, Italia; Massimo Valle, PMP Fisica, Genova, Italia; Stefania Varotto, Dipartimento di Pediatria, Università di Padova, Italia; Carmen Fiorella Stocco, Registro Tumori del Veneto, Istituto Oncologico Veneto IRCCS, Padova, Italia; Paolo Vecchia, ISS, Roma, Italia; Paola Zambon, Registro Tumori del Veneto, Università di Padova, Padova, Italia.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences (DIMEC), UO Medicina del Lavoro, S Orsola-Malpighi University Hospital, University of Bologna, Via Pelagio Palagi 9, 40138, Bologna, Italy

    Andrea Farioli & Stefano Mattioli

  2. Unit of Occupational Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy

    Patrizia Legittimo

  3. Occupational and Environmental Epidemiology Unit, ISPO Cancer Prevention and Research Institute, Florence, Italy

    Lucia Miligi & Alessandra Benvenuti

  4. Cancer Epidemiology Unit, Department of Translational Medicine, CPO Piemonte and University of Eastern Piedmont, Novara, Italy

    Alessandra Ranucci & Corrado Magnani

  5. IASI-CNR, Rome, Italy

    Alberto Salvan

  6. Paediatric Oncology-Haematology “Lalla Seràgnoli”, Policlinico S.Orsola-Malpighi, Bologna, Italy

    Roberto Rondelli

  7. Department of Pediatrics, Ospedale S. Gerardo, University of Milano-Bicocca, Monza, Italy

    Valentino Conter

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  1. Andrea Farioli
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  2. Patrizia Legittimo
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  3. Stefano Mattioli
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  4. Lucia Miligi
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  5. Alessandra Benvenuti
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  6. Alessandra Ranucci
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  7. Alberto Salvan
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  8. Roberto Rondelli
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  9. Valentino Conter
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  10. Corrado Magnani
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Corresponding author

Correspondence to Stefano Mattioli.

Additional information

On behalf of the SETIL Study Group.

Patrizia Legittimo: previously at Occupational and Environmental Epidemiology Unit, ISPO Cancer Prevention and Research Institute, Florence, Italy.

Alberto Salvan: retired.

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Farioli, A., Legittimo, P., Mattioli, S. et al. Tobacco smoke and risk of childhood acute lymphoblastic leukemia: findings from the SETIL case–control study. Cancer Causes Control 25, 683–692 (2014). https://doi.org/10.1007/s10552-014-0371-9

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