title: Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies.
abstract: The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer.
  
  
  
  We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes.
  
  
  
  Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes.
  
  
  
  PROSPERO CRD42016052762.
authors.affiliation: Department of Medicine, University of Valencia/INCLIVA Health Research Institute and CIBERSAM, Valencia, Spain. ferran_catala@hotmail.com.|Fundación Instituto de Investigación en Servicios de Salud, Valencia, Spain. ferran_catala@hotmail.com.|Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. ferran_catala@hotmail.com.
authors.forename: Ferrán
authors.initials: F
authors.lastname: Catalá-López
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA, USA.|Division of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Driver
authors.affiliation: School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Page
authors.affiliation: Instituto Aragonés de Ciencias de la Salud, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Zaragoza, Spain.|Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO-Salud Pública), Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ridao
authors.affiliation: Health Services and Policy Research Group, Exeter Collaboration for Academic Primary Care, University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: José M
authors.initials: JM
authors.lastname: Valderas
authors.affiliation: Department of History of Science and Documentation, University of Valencia, Valencia, Spain.|Unidad de Información e Investigación Social y Sanitaria-UISYS, University of Valencia-Spanish National Research Council (CSIC), Valencia, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Alonso-Arroyo
authors.affiliation: Department of Medicine, University of Valencia/INCLIVA Health Research Institute and CIBERSAM, Valencia, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Forés-Martos
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Spanish National Research Council (UMH-CSIC), San Juan de Alicante, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Martínez
authors.affiliation: Directorate General for Public Health, Regional Health Council, Madrid, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Gènova-Maleras
authors.affiliation: Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Medicines and Healthcare Products Agency (AEMPS), Madrid, Spain.|Department of Health Systems and Services, Unit of Medicines and Health Technologies, Pan American Health Organization (PAHO), Washington, DC, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Macías-Saint-Gerons
authors.affiliation: Department of Psychiatry, Hospital Marqués de Valdecilla, University of Cantabria/IDIVAL and CIBERSAM, Santander, Spain.
authors.forename: Benedicto
authors.initials: B
authors.lastname: Crespo-Facorro
authors.affiliation: Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and CIBERSAM, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.affiliation: Structural Biology and Biocumputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
authors.affiliation: Department of Medicine, University of Valencia/INCLIVA Health Research Institute and CIBERSAM, Valencia, Spain. rafael.tabares@uv.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Tabarés-Seisdedos
mesh_terms: D002493:Central Nervous System Diseases / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000453:epidemiology* / Q000401:mortality; D064887:Observational Studies as Topic; D012107:Research Design; D012196:Review Literature as Topic; D000078202:Systematic Reviews as Topic
keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Anorexia nervosa; Autism spectrum disorders; Bipolar disorder; Cancer; Central nervous system disorder; Depression; Down’s syndrome; Epilepsy; Huntington’s disease; Meta-analysis; Multiple sclerosis; Parkinson’s disease; Schizophrenia; Systematic review