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Maternal lifestyle factors and risk of neuroblastoma in the offspring: A meta-analysis including Greek NARECHEM-ST primary data
Institution:1. Department of Pediatric Hematology-Oncology, ''P&A Kyriakou'' Children''s Hospital, Athens, Greece;2. Pediatric Hematology-Oncology Unit, 1st Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Greece, ''A. Sofia'' Children''s Hospital, Greece;3. Department of Pediatric Hematology-Oncology, Hippokration Hospital, Thessaloniki, Greece;4. Department of Pediatric and Adolescent Hematology-Oncology, ''A. Sofia'' Children''s Hospital, Athens, Greece;5. Hematology-Oncology Unit, 2nd Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece;6. Department of Pediatric and Adolescent Hematology-Oncology ''Mitera'' Children''s Hospital, Athens, Greece;7. Department of Pediatric Hematology- Oncology University of Crete, University Hospital of Heraklion, Greece;8. Department of Pathology, ''A. Sofia'' Children''s Hospital, Athens, Greece;9. Pathology Laboratory, ''P&A Kyriakou'' Children''s Hospital, Athens, Greece;10. Department of CT, MRI & Nuclear Medicine, ''Aghia Sophia'' Children''s Hospital, Athens, Greece;11. Department of Neurosurgery, ''A. Sophia'' Children''s Hospital, Athens, Greece;12. Hellenic Society for Social Pediatrics and Health Promotion, Athens, Greece;1. Hellenic Society for Social Pediatrics and Health Promotion, Athens, Greece;2. Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece;3. International Agency for Research on Cancer (IARC/WHO), Lyon, France;4. Center for Evidence Synthesis in Health, Brown University School of Public Health, Providence, RI, USA;5. Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Greece;1. Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Greece;2. National Cancer Registry of Ukraine, National Institute of Cancer, Kyiv, Ukraine;3. Belarusian Research Center for Pediatric Oncology, Hematology and Immunology , Childhood Cancer Subregistry of Belarus, Minsk, Belarus;4. Bulgarian National Cancer Registry, National Oncology Hospital, Sofia, Bulgaria;5. Institute of Public Health of Serbia, Belgrade, Serbia;6. Izmir Cancer Registry, Izmir Hub, Izmir & Hacettepe University Institute of Public Health, Ankara, Turkey;7. North Region Cancer Registry of Portugal (RORENO), Portuguese Oncology Institute of Porto, Portugal;8. Croatian National Cancer Registry, Croatian Institute of Public Health, Zagreb, Croatia;9. Cancer Registry of Republic of Slovenia, Institute of Oncology, Ljubljana, Slovenia;10. Registo Oncológico Regional do Centro, Instituto Português de Oncologia de Coimbra, Francisco Gentil E.P.E, Coimbra, Portugal;11. Cyprus Cancer Registry-Health Monitoring Unit, Ministry of Health, Nicosia, Cyprus;12. Northeast Regional Cancer Registry, Regional Center of Public Health, 14 Victor Babes Street, 700465 Iasi, Romania;13. Regional Cancer Registry of Cluj, Oncological Institute “Ion Chiricuta”, Cluj-Napoca, Romania;14. Oncology Department, “Mitera” Childrens Hospital, ErythrouStavrou 6 Marousi, Athens, Greece;15. 2nd Department of Pediatrics, Aristotelion University of Thessaloniki, AHEPA General Hospital, Thessaloniki, Greece;p. Haematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, “Aghia Sophia” Children’s Hospital, Athens, Greece;q. Department of Pediatric Haematology-Oncology, “Aghia Sophia” Children’s Hospital, Athens, Greece;r. Department of Pediatric Hematology-Oncology, “Pan. & Agl. Kyriakou” Children’s Hospital, Athens, Greece;s. Department of Pediatric Hematology-Oncology, University of Crete, University Hospital of Heraklion, Heraklion, Greece;t. Department of Pediatric Hematology and Oncology, Hippokration Hospital, Thessaloniki, Greece;u. Department of Neurosurgery, “G. Gennimatas” Athens General Hospital, Athens, Greece;v. Department of Neurosurgery, “Mitera” Childrens Hospital, Erythrou Stavrou 6 Marousi, Athens, Greece;w. Department of Neurosurgery, University Hospital of Heraklion, Heraklion, Crete, Greece;x. Department of Neurosurgery, St. Luke’s Hospital, Panorama, Thessaloniki, Greece;y. First Department of Radiology, Aretaieion Hospital, Medical School, University of Athens, Athens, Greece;z. 2nd Department of Radiology, Radiotherapy Unit, Medical School, National Kapodistrian University of Athens, Athens, Greece;11. Department of Radiology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece;12. Department of Pathology, “G. Gennimatas” Athens General Hospital, Athens, Greece;13. Department of Pathology, Hygeia Hospital, Athens, Greece;14. Histopathology Department, “Aghia Sophia” Children’s Hospital, Athens, Greece;15. Histopathology Department, “Pan. & Agl. Kyriakou” Children’s Hospital, Athens, Greece;16. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain;17. Universitat Pompeu Fabra (UPF), Barcelona, Spain;18. CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain;19. Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France;1. Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Greece;2. National Cancer Registry of Ukraine, National Institute of Cancer, Kyiv, Ukraine;3. Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Childhood Cancer Subregistry of Belarus, Minsk, Belarus;4. Bulgarian National Cancer Registry, National Oncology Hospital, Sofia, Bulgaria;5. Institute of Public Health of Serbia, Belgrade, Serbia;6. Izmir Cancer Registry, Izmir Hub, Izmir & Hacettepe University Institute of Public Health, Ankara, Turkey;7. North Region Cancer Registry of Portugal (NORTH), Portuguese Oncology Institute of Porto, Portugal;8. Croatian National Cancer Registry, Croatian Institute of Public Health, Zagreb, Croatia;9. Cancer Registry of Republic of Slovenia, Institute of Oncology, Ljubljana, Slovenia;10. Registo Oncológico Regional do Centro, Instituto Português de Oncologia de Coimbra Francisco Gentil E.P.E, Coimbra, Portugal;11. Cyprus Cancer Registry-Health Monitoring Unit, Ministry of Health, Nicosia, Cyprus;12. Malta National Cancer Registry, Department of Health Information and Research, Malta;13. Epidemiology, Institute of Public Health, 16-18 Victor Babes Street, Timisoara 300226, Romania;14. Regional Cancer Registry of Cluj, Oncological Institute “Ion Chiricuta”, Cluj-Napoca, Romania;15. Oncology Department, “Mitera” Childrens Hospital, Erythrou Stavrou 6 Marousi, Athens, Greece;p. 2nd Department of Pediatrics, Aristotelion University of Thessaloniki, AHEPA General Hospital, Thessaloniki, Greece;q. Department of Pediatric Hematology and Oncology, Hippokration Hospital, Thessaloniki, Greece;r. Department of Pediatric Haematology-Oncology, “Aghia Sophia” Children’s Hospital, Athens, Greece;s. Department of Pediatric Hematology-Oncology, “Pan. & Agl. Kyriakou” Children’s Hospital, Athens, Greece;t. Department of Pediatric Hematology-Oncology, University of Crete, University Hospital of Heraklion, Heraklion, Greece;u. First Department of Radiology, Aretaieion Hospital, Medical School, University of Athens, Athens, Greece;v. Department of Neurosurgery, University Hospital of Heraklion, Heraklion, Crete, Greece;w. Department of Neurosurgery, G. Gennimatas General Hospital, Athens, Greece;x. Department of Pathology, Hygeia Hospital, Athens, Greece;y. 2nd Department of Radiology, Radiotherapy Unit, Medical School, National Kapodistrian University of Athens, Athens, Greece;z. Department of Pathology, National and Kapodistrian University of Athens, Medical School, Athens, Greece;11. Department of Neurosurgery, “Mitera” Childrens Hospital, Erythrou Stavrou 6 Marousi, Athens, Greece;12. Department of Neurosurgery, St. Luke’s Hospital, Panorama, Thessaloniki;13. Haematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, “Aghia Sophia” Children’s Hospital, Athens, Greece;14. Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France;1. Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece;2. Department of Chronic Disease Epidemiology, Yale School of Public Health, Cancer Prevention and Control, Yale Comprehensive Cancer Centre, Yale School of Medicine, CT, USA;3. Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA;4. CRESS, UMR-S1153, INSERM, Paris-Descartes University, Villejuif, France;5. National Registry of Childhood Cancers, APHP, Hôpital Paul-Brousse, CHU de Nancy, France;6. Pediatric Hematology-Oncology Program Instituto Nacional de Cancer, Rio de Janeiro, Brazil;7. Department of Epidemiology, School of Public Health, University of California, Los Angeles, CA, USA;8. Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, Heslington, York, United Kingdom;9. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;10. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA;11. Danish Cancer Society Research Center, Copenhagen, Denmark;12. Faculty of Social Sciences, University of Tampere, Tampere, Finland;13. Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan;14. International Agency for Research on Cancer (IARC), Section of Environment and Radiation, Lyon, France;15. Cancer Epidemiology Unit, Department of Translational Medicine, CPO Piedmont and University of Eastern Piedmont, Novara, Italy;p. Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica;q. Department of Preventative and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand;r. Baylor College of Medicine, Department of Pediatrics Texas Children''s Cancer Center, TX, USA;s. Danish Cancer Society Research Center, Childhood Cancer Research Group, Copenhagen, Denmark;t. School of Public Health, University of California, Berkeley, CA, USA;u. Telethon Institute for Child Health Research, Center for Child Health Research, University of Western Australia, WA, Australia;v. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden;1. Environmental Epidemiology of Cancer, CESP, U1018, Inserm, Villejuif, France;2. Epidemiology & Cancer Statistics Group, Department of Health Sciences, University of York, York YO10 5DD, United Kingdom;2. Department of Pediatric Hematology/Oncology, Agia Sofia Children''s Hospital, Athens, Greece;3. Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium;4. University Medical Center Utrecht, Wilhelmina Children''s Hospital, Utrecht, the Netherlands;5. Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Abstract:The etiology of childhood neuroblastoma remains largely unknown. In this systematic review and meta-analysis, we summarized and quantitatively synthesized published evidence on the association of maternal modifiable lifestyle factors with neuroblastoma risk in the offspring. We searched MEDLINE up to December 31, 2020 for eligible studies assessing the association of maternal smoking, alcohol consumption and nutritional supplementation during pregnancy with childhood (0–14 years) neuroblastoma risk. Random-effects models were run, and summary odds ratios (OR) and 95% confidence intervals (95% CI) on the relevant associations were calculated, including estimates derived from primary data (n = 103 cases and n = 103 controls) of the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) case control study (2009–2017) in Greece. Twenty-one eligible studies amounting 5163 cases participating in both case-control and cohort/linkage studies were included in the meta-analysis. Maternal smoking and alcohol consumption were not statistically significantly associated with neuroblastoma risk (summary ORsmoking: 1.08, 95% CI: 0.96–1.22, I2 =12.0%, n = 17 studies; summary ORalcohol: 1.01, 95% CI: 0.82–1.18, I2 =0.0%, n = 8 studies). By contrast, maternal vitamin intake during pregnancy was associated with significantly lower neuroblastoma risk (summary OR: 0.57, 95% CI: 0.34–0.95, I2 =58.9%, n = 4 studies). The results of the largest to-date meta-analysis point to an inverse association between vitamin intake during pregnancy and childhood neuroblastoma risk. Future longitudinal studies are needed to confirm and further specify these associations as to guide preventive efforts on modifiable maternal risk factors of childhood neuroblastoma.
Keywords:Neuroblastoma  Children  Lifestyle factors  Vitamins  Systematic review
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