RESUMO
After decades of unawareness about Lynch syndrome, the medical community in South America is increasingly interested and informed. The visits and support of mentors like H. T. Lynch had been crucial to this awakening. Several countries have at least one registry with skilled personnel in genetic counseling and research. However, this only represents a very restricted resource for the region. According to the GETH, there are 27 hereditary cancer care centers in South America (21 in Brazil, 3 in Argentina, 1 in Uruguay, 1 in Chile and 1 in Peru). These registries differ in fundamental aspects of function, capabilities and funding, but are able to conduct high quality clinical, research and educational activities due to the dedication and personal effort of their members, and organizational support. More support from the governments as well as the participation of the community would boost the initiatives of people leading these groups. Meantime, the collaboration among the South American registries and the involvement of registries and leaders from developed countries will allow to maximize the efficiency in caring for affected patients and their families. The aim of this article is to describe how the knowledge of LS began to be spread in South America, how the first registries were organized and to summarize the current state of progress. In addition, we will provide an update of the clinical and molecular findings in the region.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Aconselhamento Genético/estatística & dados numéricos , Aconselhamento Genético/tendências , Predisposição Genética para Doença , Testes Genéticos , Sistema de Registros/estatística & dados numéricos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Mutação em Linhagem Germinativa , América do Sul/epidemiologiaRESUMO
PURPOSE: The first Argentine experience with epidemiologic, molecular, and genetic counseling data is reported. METHODS: We analyzed 43 families fulfilling Amsterdam criteria identified from a prospective database with data from 779 relatives. RESULTS: Eleven families (25.6 percent) presented as Lynch I, 29 (67.4 percent) as Lynch II, and 3 (7 percent) as Muir-Torre syndrome. Among the 306 affected members, 197 cases of colorectal cancer were identified (mean age at diagnosis, 52.1 (range, 21-90) years). The most frequent extracolonic tumors were gastric adenocarcinoma in males and endometrium adenocarcinoma in females. A high incidence of breast cancer was observed (16 cases among 155 females, crude rate: 11,594.20/100,000). Twenty-seven patients (8.8 percent) developed more than one tumor. These patients were younger than those with only one tumor (45 vs. 51 years; P = 0.001). In 5 of 11 patients who underwent molecular sequencing, a pathologic mutation was found. A novel C deletion at 1910 nucleotide, codon 637, exon 12 of MSH2 gene was identified in a family with a strong aggregation of breast cancer with lack of MSH2 immunohistochemical staining. For 78.2 percent of counseled individuals, this session represented the first time they received information, and 73.9 percent stated that their physicians were unaware of their family background. CONCLUSIONS: Argentine families presented a high incidence of stomach cancer. The elevated incidence of breast cancer and its association with a novel hMSH2 mutation bring to consideration the inclusion of this malignancy as part of the syndrome. A lack of awareness by both physicians and persons at risk was observed.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Proteína 2 Homóloga a MutS/genética , Mutação/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Feminino , Aconselhamento Genético , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Linhagem , Encaminhamento e Consulta , Sistema de RegistrosAssuntos
Masculino , Feminino , Humanos , Neoplasias Colorretais , Mutação/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/etiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/prevenção & controleRESUMO
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colorectal cancer (CRC). Our purpose is to describe three extended HNPCC families, each of which manifests novel germline mutations in Uruguay, a small country that is a study model for cancer investigation given its high cancer incidence and mortality rate. This is a study of three extended HNPCC families in which extensive genealogic information, medical history, and pathology findings are critically reviewed. DNA testing was performed for evidence of HNPCC mutations. The findings reveal three novel germline mutations, namely MLH1, with a deletion resulting in a frameshift and a premature stop codon (codon 228) in one of the families; in the second family, MSH2 exon 1, codon 61 at nucleotide 181, which results in immediate stop of translation; and in the third family, a mutation in MSH2 at exon 3: the amino acid at nucleotide 530, codon 117, causing a frameshift and a premature stop codon eight base pairs later. We conclude that it is important to study HNPCC mismatch repair genes because of emerging evidence for genotypic and phenotypic heterogeneity, which will harbor the potential to eventually translate this knowledge into specific screening and management protocols. Future projections for such mutations could even contribute to the emergence of molecular-based designer drugs developed through advances in genomics, proteomics, high-throughput screening, and bioinformatics, which would be effective therapeutically for these high-cancer risk patients.