title: Contribution of the TP53 R337H mutation to the cancer burden in southern Brazil: Insights from the study of 55 families of children with adrenocortical tumors.
abstract: BACKGROUND
  The tumor protein p53 (TP53) arginine-to-histidine mutation at codon 337 (R337H) predisposes children to adrenocortical tumors (ACTs) and, rarely, to other childhood tumors, but its impact on adult cancer remains undetermined. The objective of this study was to investigate the frequency and types of cancer in relatives of children with ACT who carry the TP53 R337H mutation.
  
  
  METHODS
  TP53 R337H testing was offered to relatives of probands with ACT. The parental lineage segregating the R337H mutation was identified in all families. The frequency and distribution of cancer types were compared according to R337H status. The authors' data also were compared with those publicly available for children with TP53 mutations other than R337H.
  
  
  RESULTS
  The mean and median follow-up times for the probands with ACT were 11.2 years and 9.7 years (range, 3-32 years), respectively. During this time, cancer was diagnosed in 12 of 81 first-degree relatives (14.8%) carrying the R337H mutation but in only 1 of 94 noncarriers (1.1%; P = .0022). At age 45 years, the cumulative risk of cancer was 21% (95% confidence interval, 5%-33%) in carriers and 2% (95% confidence interval, 0%-4%) in noncarriers (P = .008). The frequency of cancer was higher in the R337H segregating lineages than in the nonsegregating lineages (249 of 1410 vs 66 of 984 individuals; P < .001). Breast and gastric cancer were the most common types.
  
  
  CONCLUSIONS
  TP53 R337H carriers have a lifelong predisposition to cancer with a bimodal age distribution: 1 peak, represented by ACT, occurs in the first decade of life, and another peak of diverse cancer types occurs in the fifth decade. The current findings have implications for genetic counseling and surveillance of R337H carriers. Cancer 2017;123:3150-58. © 2017 American Cancer Society.
authors.affiliation: Graduate Program in Child and Adolescent Health, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.|Pediatric Oncology Department, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Maria J
authors.identifier: http://orcid.org/0000-0003-1641-7727
authors.initials: MJ
authors.lastname: Mastellaro
authors.affiliation: Medical Genetics Department, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.|Molecular Biology Laboratory, Boldrini Children's Center, Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Seidinger
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Guolian
authors.initials: G
authors.lastname: Kang
authors.affiliation: Department of Noncommunicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Renata
authors.initials: R
authors.lastname: Abrahão
authors.affiliation: Data Center and Statistics, Hematology and Hemotherapy Department, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Eliana C M
authors.initials: ECM
authors.lastname: Miranda
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Stanley B
authors.identifier: http://orcid.org/0000-0002-9167-2114
authors.initials: SB
authors.lastname: Pounds
authors.affiliation: Department of Pathology, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Izilda A
authors.initials: IA
authors.lastname: Cardinalli
authors.affiliation: Pediatric Oncology Department, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.|Center for Pediatrics Research (CIPED), University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Simone S
authors.initials: SS
authors.lastname: Aguiar
authors.affiliation: Federal University of Parana and Pele Pequeno Principe Research Institute, Curitiba, Parana, Brazil.
authors.forename: Bonald C
authors.initials: BC
authors.lastname: Figueiredo
authors.affiliation: Department of Global Medicine, International Outreach Program, St Jude Children's Research Hospital, Memphis, Tennessee.|Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.affiliation: Department of Oncology and Hematology, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Silvia R
authors.initials: SR
authors.lastname: Brandalise
authors.affiliation: Medical Genetics Department, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.|Molecular Biology Laboratory, Boldrini Children's Center, Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Yunes
authors.affiliation: Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Antônio de A
authors.initials: AA
authors.lastname: Barros-Filho
authors.affiliation: Department of Global Medicine, International Outreach Program, St Jude Children's Research Hospital, Memphis, Tennessee.|Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D000328:Adult; D001938:Brazil; D001943:Breast Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: adrenocortical tumors; arginine-to-histidine mutation at codon 337 (R337H); childhood cancer; familial cancer; gastric cancer; tumor protein p53 (TP53)