Germline TP53 p.R337H and XAF1 p.E134* Variants: Prevalence in Paraguay and Comparison with Rates in Brazilian State of Paraná and Previous Findings at the Paraguayan-Brazilian Border.

Adrenal cortex carcinoma (ACC) in children is a rare tumor that is probably of multifactorial origin and is mainly associated with genetic and environmental alterations. In the south and part of the southeast of Brazil, as well as in the Paraguayan region bordering the Brazilian State of Paraná, ACC prevalence is higher than in any other country, which is associated with the high prevalence of the TP53 p.R337H variant in Paraná (0.30%), Santa Catarina (0.249%), cities around Campinas-SP (0.21%), and the Paraguayan cities on the border with Paraná (0.05%). Recent research suggests that the co-segregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone. Breast cancer may be mildly influenced by co-segregation with XAF1 p.E134*, and this variant can also confer risk for sarcoma.

objectivesThe objectives of this study were to (1) estimate the prevalence of the germline TP53 p.R337H and XAF1 p.E134* variants in Paraguay (excluding cities on the border with Paraná State, Brazil) and (2) estimate whether the ethnic origin of TP53 p.R337H carriers in Paraguay is similar to that of ethnic groups in Paraná (possible Portuguese/Spanish origin). MATERIALS AND

methodsDNA tests for the identification of TP53 p.R337H were carried out from 2016 to 2019 at the Bio-Materials Laboratory of Facultad Politecnica, UNA, and at the Research Center in Biotechnology and Informatics (CEBIOTEC), Asunción, Paraguay. Polymerase chain reaction followed by restriction enzyme digestion (PCR-RFLP) was used to identify TP53 p.R337H, and real-time PCR (RT-PCR) was employed for XAF1 p.E134*. Peripheral blood samples from 40,000 Paraguayan newborns (NBs) were used for the TP53 p.R337H tests. The XAF1 p.E134* tests (RT-PCR) were performed on samples from 2000 Paraguayan newborns at the Pelé Pequeno Principe Research Institute, Curitiba, PR, Brazil.

resultsThe TP53 p.R337H variant was not found in any of the 14 Paraguayan departments investigated. A total of 12 of the 2000 Paraguayan NBs were positive for one XAF1 p.E134* allele.

conclusionsThe hypothesis of Spanish immigrants carrying p.R337H to Paraguay was disproved. TP53 p.R337H neonatal testing in Paraguay is not recommended, except when there are families with Brazilian ancestry presenting cancer cases. Additional epidemiological studies are required to determine the likelihood of the identified prevalence of the XAF1 p.E134* allele (1/153) in NBs from Paraguay without TP53 p.R337H to present cancer risk. This study complements the first national initiative for the DNA screening of newborns aimed at mapping the TP53 p.R337H and XAF1 p.E134* variants in Paraguay (based on the regions of residence of the newborns).