Prevalence of an inherited cancer predisposition syndrome associated with the germ line TP53 R337H mutation in Paraguay.
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer, and the germline TP53 R337H mutation is the most common mutation reported to date. However, this mutation is associated with a lower cumulative lifetime cancer risk than other mutations in the p53 DNA-binding domain. A detailed statistical analysis of 171,500 DNA tests in Brazilian neonates found that 0.27% of the general population is positive for this mutation, and some of the estimated 200,000 Brazilian R337H carriers in southern and southeastern Brazil have already developed cancer. The present study was designed to estimate R337H prevalence in neighboring Paraguay. To address this question, 10,000 dried blood samples stored in Guthrie cards since 2008 were randomly selected from the Paraguayan municipalities located at the border with Brazil. These samples were tested for R337H mutation using the PCR-restriction fragment length polymorphism assay. This germline mutation was detected in five samples (5/10,000), indicating that the total number of R337H carriers in Paraguay may be as high as 3500. Previous studies have shown that other countries (i.e., Portugal, Spain, and Germany) presented one family with this mutation, leading us to conclude that, besides Brazil and Paraguay, other countries may have multiple families carrying this mutation, which is an inherited syndrome that is difficult to control.
Laboratorio de Bio y Materiales, NIDTEC, Facultad Politécnica, Universidad Nacional de Asunción, Campus UNA, CP 2160 San Lorenzo, Paraguay; Instituto de Pesquisa Pelé Pequeno Príncipe, Avenida Silva Jardim, 1632, Água Verde, Curitiba, Paraná, Brazil; Faculdades Pequeno Príncipe, Avenida Silva Jardim, 1632, Água Verde, Curitiba, Paraná, Brazil. Electronic address: eafalcon@brturbo.com.br.
Edith Falcon-de
EF
Legal
Programa de Prevención de la Fibrosis Quística y del Retardo Mental, Centro de Salud N° 9, Ministerio de Salud Pública y Bienestar Social, Herminio Giménez c/Gral. Aguiar, Asunción, Paraguay. Electronic address: marta.ascurra@gmail.com.
Marta
M
Ascurra
Instituto de Pesquisa Pelé Pequeno Príncipe, Avenida Silva Jardim, 1632, Água Verde, Curitiba, Paraná, Brazil. Electronic address: custodio.gislaine@gmail.com.
Gislaine
G
Custódio
Laboratorio de Computación Científica y Aplicada, NIDTEC, Facultad Politécnica, Universidad Nacional de Asunción, Campus UNA, CP 2160 San Lorenzo, Paraguay. Electronic address: hlegal@pol.una.py.
Horacio Legal
HL
Ayala
Laboratorio de Bio y Materiales, NIDTEC, Facultad Politécnica, Universidad Nacional de Asunción, Campus UNA, CP 2160 San Lorenzo, Paraguay. Electronic address: mmonteiro@pol.una.py.
Magna
M
Monteiro
Centro para el Desarrollo de la Investigación Científica - CEDIC, Manduvira 635 entre 15 de Agosto y O'leary, CP 1255 Asunción, Paraguay. Electronic address: mcvegagomez@gmail.com.
Celeste
C
Vega
Laboratorio de Computación Científica y Aplicada, NIDTEC, Facultad Politécnica, Universidad Nacional de Asunción, Campus UNA, CP 2160 San Lorenzo, Paraguay. Electronic address: mjfernandez@pol.una.py.
María José
MJ
Fernández-Nestosa
Centro de Endocrinología y Prevención de Diabetes - CEYPED, 22 de Setiembre 905, CP 1564 Asunción, Paraguay. Electronic address: sonia.vega@ceyped.com.
Sonia
S
Vega
Instituto de Pesquisa Pelé Pequeno Príncipe, Avenida Silva Jardim, 1632, Água Verde, Curitiba, Paraná, Brazil; Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC), Rua Agostinho Leão Júnior, 400, Glória, Curitiba, Paraná, Brazil. Electronic address: elisrosane@hotmail.com.
Elis R
ER
Sade
Faculdades Pequeno Príncipe, Avenida Silva Jardim, 1632, Água Verde, Curitiba, Paraná, Brazil. Electronic address: izabel.coelho@fpp.edu.br.
Izabel M M
IM
Coelho
Departamento de Genética, Centro Politécnico, Jardim das Américas, Caixa Postal 19071, Curitiba, PR, Brazil. Electronic address: enilzeribeiro@gmail.com.
Enilze M S F
EM
Ribeiro
Departamento de Genética, Centro Politécnico, Jardim das Américas, Caixa Postal 19071, Curitiba, PR, Brazil. Electronic address: cavalli@ufpr.br.
Iglenir J
IJ
Cavalli
Instituto de Pesquisa Pelé Pequeno Príncipe, Avenida Silva Jardim, 1632, Água Verde, Curitiba, Paraná, Brazil; Faculdades Pequeno Príncipe, Avenida Silva Jardim, 1632, Água Verde, Curitiba, Paraná, Brazil; Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC), Rua Agostinho Leão Júnior, 400, Glória, Curitiba, Paraná, Brazil; Departamento de Saúde Comunitária, Universidade Federal do Paraná, Rua Padre Camargo, 280, 7° andar, Curitiba, PR, Brazil. Electronic address: bonald.figueiredo@fpp.edu.br.
Bonald C
BC
Figueiredo
D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D010239:Paraguay; D015995:Prevalence; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53
Cancer; Li–Fraumeni syndrome; TP53 R337H mutation