Banca de DEFESA: MARIANA NOVAES SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : MARIANA NOVAES SANTOS
DATE: 12/12/2022
TIME: 14:30
LOCAL: Universidade Federal de Alagoas
TITLE:

Familial Adenomatous Polyposis in Alagoas

KEY WORDS:

Hereditary Neoplastic Syndromes, Adenomatous Polyposis Coli, APC Gene, Rare Diseases, Development Indicators, Health Literacy.

PAGES: 150
BIG AREA: Ciências Biológicas
AREA: Genética
SUBÁREA: Genética Humana e Médica
SUMMARY:

Background: Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome caused by germline variants of APC gene, with autosomal dominant inheritance and nearly complete penetrance of colorectal cancer if left untreated. The global care of patients with FAP includes timely prevention, diagnosis and surgical intervention strategies. Thus, the reduction of systemic barriers in the access of patients to information and healthcare is critical to disease management. This research was the first step for the knowledge of the molecular epidemiology of hereditary colorectal cancer syndromes in Alagoas and it focuses on the study of a family with multiple individuals affected by intermediate FAP. It aims to describe socioeconomic, health literacy, clinical and genetic characteristics of this family. Methods: his cross-sectional and observational study enrolled 54 participants. Data was collected through an inhouse clinical and socioeconomic questionnaire, the Brazilian-validated Health Literacy Test (from Portuguese, TLS), which scores from 0 to 100. Additionally, the medical records of the family members followed at the University Hospital of Federal University of Alagoas were reviewed and pedigree draft and biologic samples for family’s variant identification were obtained. Socioeconomic data will be used for the Family Development Index (from Portuguese, IDF) calculation, which scores from 0 to 1. IDF and TLS scores and clinical data were recorded on Excel and were descriptively analyzed using the statistical program JASP. Genes of interest were screened by next-generation sequencing in the index case. Results were confirmed through Sanger sequencing in the index case and allele-specific polymerase chain reaction (PCR) in four affected participants and three negative controls (intra and extrafamilial). In silico pathogenicity prediction analysis of the identified variant was performed. Results: Three hundred and twenty-seven individuals, with 32 living affected relatives, were mapped through the pedigree analysis. analysis. Most of them lived 5 km away from the healthcare unit in poor houses, with no piped water and electricity until a few years ago. The mean IDF was 0.476 and the TLS score was 23.4. Among the 54 interviewed, fourteen were diagnosed with FAP and had, in general, late diagnosis and inadequate management and surveillance. The APC heterozygous germline variant c.1255del (p.Thr419Profs*35), which has never been previously reported, was identified in the affected participants. In silico analysis confirmed the pathogenicity of the genetic alteration, since it leads to early truncation and loss of all functional domains of APC protein. Conclusions: Difficult access to healthcare services, low health literacy and economic conditions were the major patient-level barriers to global care  identified. The analysis of the genetic data enabled the identification of the genetic causing variant of FAP in this family, the confirmation of its autosomal dominant segregation and the development of a specific molecular diagnostic test, which is available for all interested relatives, after pre-test genetics counseling. Serving as translational research, a partnership with the Municipal Health Department was established and the study results might be used to overcome barriers aiming to improve individual and collective global care.

BANKING MEMBERS:
Interno(a) - 3221982 - ISABELLA LOPES MONLLEO
Interno(a) - 2370894 - MICHELLE JACINTHA CAVALCANTE OLIVEIRA
Externo(a) à Instituição - LAVÍNIA SCHULER FACCINI
Externo(a) à Instituição - BENEDITO MAURO ROSSI