Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil

Cancers

JaquelineD. C. Passos¹  AmandaF. Cruz¹  KarinaC. F. Tosin¹  MirnaM. O. Figueiredo¹  LauraM. Castilho¹  Gislaine Custódio¹  GuilhermeA. Parise¹  ThuilaF. da Maia¹  TâniaL. Mazzuco²  AnaL. M. R. Fabro³  EdithF. Legal³  DeniseB. da Silva⁴  SylvioG. A. Ávilla⁵  CesarC. Sabbaga⁵  Leila Grisa⁵  FloraM. Watanabe⁵  Nilton Kiesel Filho⁵  AnaPaula Kuczynski⁵  Edna Carboni⁵  Airton Aranha⁵  CarmemM. C. M. Fiori⁶  JoséH. G. Balbinotti⁷  Roberto Rosati⁷  HumbertoC. Ibañez⁷  VivianeK. Q. Gerber⁷  KarinR. P. Ogradowski⁷  Cleber Machado-Souza⁷  AndréL. Grion⁷  IvyZ. S. Parise⁷  Heloisa Komechen⁷  BonaldC. Figueiredo⁷  RosianeG. Melo⁷  KarinL. Dammski⁷  EmanuelleN. Souza⁷  MarileaV. C. Ibañez⁷  TatianaE. J. Costa⁷  MarianaM. Paraizo⁷  Geneci Lima⁷  MonalisaC. Mendes⁷  JoséR. S. Barbosa⁷  DiancarlosP. Andrade⁷  ClaudiaS. Oliveira⁷  MaraA. D. Pianovski⁸  Leniza Lima⁸  Tiago Tormen⁸  TaniaH. Anegawa⁹  VivianeS. Melanda^1,10 

[1] Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC-APACN), Av. Agostinho Leão Junior, 400, Alto da Glória, Curitiba 80030-110, PR, Brazil;Divisão de Endocrinologia, Departamento de Clínica Médica, Universidade Estadual de Londrina, Rua Robert Koch, 60, Vila Operária, Londrina 86038-350, PR, Brazil;Faculdades Pequeno Príncipe, Av. Iguaçu, 333, Rebouças, Curitiba 80230-020, Brazil;Hospital Infantil Joana de Gusmão, R. Rui Barbosa, 152, Agronômica, Florianópolis 88025-301, SC, Brazil;Hospital Pequeno Príncipe, Rua Desembargador Motta, 1070, Água Verde, Curitiba 80250-060, PR, Brazil;Hospital do Câncer, UOPECCAN, R. Itaquatiaras, 769, Santo Onofre, Cascavel 85806-300, PR, Brazil;Instituto de Pesquisa Pelé Pequeno Príncipe, Av. Silva Jardim, 1632, Curitiba 80250-060, PR, Brazil;Oncologia Pediátrica, Hospital Erasto Gaertner, R. 201, Jardim das Américas, Curitiba 81520-060, PR, Brazil;Oncologia Pediátrica, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid-PR 445 Km 380, Campus Universitário, Londrina 86057-970, PR, Brazil;Secretaria do Estado da Saúde do Paraná, R. Piquiri, 170, Rebouças, Curitiba 80230-140, PR, Brazil;

关键词: r337h;    tp53;    li–fraumeni syndrome;    adrenocortical carcinoma;    children;    environmental modifiers;   

DOI  :  10.3390/cancers11111804

来源: DOAJ

【 摘 要 】

The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates.

【 授权许可】

Unknown