Polipose adenomatosa familiar em Alagoas

Abstract

Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome caused by germline variants on 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 focused on the study of a family with multiple individuals affected by intermediate FAP. It aimed to describe clinical, socioeconomic, health literacy, psychological and genetic characteristics of this family. Therefore, this cross-sectional and observational study enrolled 59 participants. Data was collected through an inhouse clinical and socioeconomic questionnaire, followed by the Brazilian-validated Health Literacy Test (from Portuguese, TLS), which scores from 0 to 100, and a guided interview about the psychological aspects of FAP. Additionally, pedigree draft and biologic samples for family’s variant identification were obtained. Socioeconomic data were used to calculate the Familial Development Index (from Portuguese, IDF), which scores from 0 to 1. Clinical data and IDF and TLS scores were recorded on Excel and descriptively analyzed using the statistical program JASP. Psychological data were qualitatively analyzed. Genes of interest were screened by next-generation sequencing in an index case. Results were confirmed through Sanger sequencing in the index case and allele-specific polymerase chain reaction in four affected participants and two negative controls (intra and extrafamilial). In silico pathogenicity prediction analysis of the identified variant was performed. Three hundred and twenty-seven family members, including 46 affected by FAP, were mapped trough pedigree analysis. Among the 59 interviewed participants, fourteen were affected by FAP and had a high mean age of diagnosis, as well as inadequate surveillance and treatment. Most of them lived 5 km away from the healthcare unit in poor houses, with no access to piped water and electricity until a few years ago. The mean IDF was 0.476 and the mean TLS score was 23,4. Psychological data analysis showed that subjective implications for the family members are heterogeneous, either between domestic nuclei and individually. The APC heterozygous germline variant c.1255delA(p.Thr419Profs*35), which had 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. In conclusion, difficult access to healthcare services, low health literacy and economic conditions were major patient-level barriers identified. The qualitative analysis illustrated the importance of the subjective approach on the global care of persons with FAP in the Brazilian public health system. Through the genetic data analysis, it was possible to identify the causative variant of FAP in this family, to confirm its autosomal dominant segregation and to develop a specific molecular diagnostic test, which is currently available to any interested relatives after pre-test genetic counseling.