title: Cancer Risk in Beckwith-Wiedemann Syndrome: A Systematic Review and Meta-Analysis Outlining a Novel (Epi)Genotype Specific Histotype Targeted Screening Protocol.
abstract: To compare tumor risk in the 4 Beckwith-Wiedemann syndrome (BWS) molecular subgroups: Imprinting Control Region 1 Gain of Methylation (ICR1-GoM), Imprinting Control Region 2 Loss of Methylation (ICR2-LoM), Chromosome 11p15 Paternal Uniparental Disomy (UPD), and Cyclin-Dependent Kinase Inhibitor 1C gene (CDKN1C) mutation.
  
  
  
  Studies on BWS and tumor development published between 2000 and 2015 providing (epi)genotype-cancer correlations with histotype data were reviewed and meta-analysed with cancer histotypes as measured outcome and (epi)genotype as exposure.
  
  
  
  A total of 1370 patients with BWS were included: 102 developed neoplasms (7.4%). Tumor prevalence was 2.5% in ICR2-LoM, 13.8% in UPD, 22.8% in ICR1-GoM, and 8.6% in patients with CDKN1C mutations. Cancer ORs were 12.8 in ICR1-GoM, 6.5 in UPD, and 2.9 in patients with CDKN1C mutations compared with patients with ICR2-LoM. Wilms tumor was associated with ICR1-GoM (OR 68.3) and UPD (OR 13.2). UPD also was associated with hepatoblastoma (OR 5.2) and adrenal carcinoma (OR 7.0), and CDKN1C mutations with neuroblastic tumors (OR 7.2).
  
  
  
  Cancer screening in BWS could be differentiated on the basis of (epi)genotype and target specific histotypes. Patients with ICR1-GoM and UPD should undergo renal ultrasonography scanning, given their risk of Wilms tumor. Alpha feto protein monitoring for heptaoblastoma is suggested in patients with UPD. Adrenal carcinoma may deserve screening in patients with UPD. Patients with CDKN1C mutations may deserve neuroblastoma screening based on urinary markers and ultrasonography scanning. Finally, screening appears questionable in cases of ICR2-LoM, given low tumor risk.
authors.affiliation: Department of Pediatric and Public Health Sciences, University of Torino, Torino, Italy. Electronic address: alessandro.mussa@unito.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mussa
authors.affiliation: Department of Pediatric and Public Health Sciences, University of Torino, Torino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Molinatto
authors.affiliation: Department of Pediatric and Public Health Sciences, University of Torino, Torino, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Baldassarre
authors.affiliation: Department of Pediatric and Public Health Sciences, University of Torino, Torino, Italy.
authors.forename: Evelise
authors.initials: E
authors.lastname: Riberi
authors.affiliation: Laboratory of Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
authors.affiliation: Laboratory of Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences, Second University of Naples and Institute of Genetics and Biophysics "A. Buzzati-Traverso", CNR, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Riccio
authors.affiliation: Department of Pediatric and Public Health Sciences, University of Torino, Torino, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Ferrero
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002985:Clinical Protocols; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000145:classification / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic
keywords: Beckwith-Wiedemann; meta-analysis; molecular group and tumor risk; oncological surveillance; tumor screening