RESUMO
BACKGROUND: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS: One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION: These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.
Assuntos
Adenocarcinoma , Polipose Adenomatosa do Colo , DNA Glicosilases , Neoplasias Gástricas , Humanos , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/terapia , Polipose Adenomatosa do Colo/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/terapia , Adenocarcinoma/diagnóstico , DNA Glicosilases/genética , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Síndromes Neoplásicas Hereditárias/diagnóstico , Europa (Continente) , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/terapia , PóliposRESUMO
The increase in demand for clinical cancer genetics services has impacted the ability to provide services timeously. Given limited resources, this often results in extended appointment waiting times. Over the last 3 years, the Cancer Genetics Service at the National Cancer Centre Singapore has continued to experience a steady increase in demand for its service. Nevertheless, significant no-show rates have been reported. This study sought to determine whether an association exists between appointment waiting times and attendance rates. Data was gathered for all participants meeting inclusion criteria. Attendance rates and appointment waiting times were calculated. The relationship between mean waiting times for those who did and did not attend their scheduled appointments was evaluated using Welch's t test and linear regression model. The results showed a significant difference in mean appointment waiting times between patients who did and did not attend (32.66 versus 43.50 days respectively; p < 0.0001). Furthermore, patients who waited for longer than 37 days were significantly less likely to attend. No-show rates increased as the waiting time increased, at a rate of 19.60% per 20 days and 21.40% per 30 days. In conclusion, appointment waiting time is a significant predictor for patient attendance. Strategies to ensure patients receive an appointment within the necessary timeframe at the desired setting are important to ensure that individuals at increased cancer risk attend their appointments in order to manage their cancer risks effectively.
Assuntos
Agendamento de Consultas , Testes Genéticos/estatística & dados numéricos , Neoplasias/genética , Pacientes não Comparecentes/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
About 5% of gastric cancers are associated with hereditary cancer syndromes. Histology is paramount in this context, as major susceptibility genes are associated with specific subtypes. Germline pathogenic variants in CDH1 and CTNNA1 cause Hereditary Diffuse Gastric Cancer (HDGC). Major advances have been made in the past ten years regarding HDGC. Penetrance estimates for diffuse cancer are now lower than previously thought, at 30-40%. Surveillance upper gastrointestinal endoscopy is now an acceptable alternative to prophylactic total gastrectomy. Indeed, its sensitivity in detecting advanced disease is satisfactory assuming it is performed by an expert and according to a specific protocol. The risk of intestinal-type gastric cancer is increased in patients with Lynch syndrome, although it is much lower than the risk of colorectal and endometrial cancer. Intestinal-type gastric cancers are also observed in excess in patients with hereditary polyposis, the main one being APC-associated familial adenomatous polyposis. The main and most clinically relevant manifestations in patients with polyposes remain colorectal and duodenal polyps and carcinomas, well ahead of gastric cancer. Finally, recent data point towards increased gastric cancer risk in hereditary breast and ovarian cancer.
Assuntos
Polipose Adenomatosa do Colo , Neoplasias Colorretais Hereditárias sem Polipose , Síndromes Neoplásicas Hereditárias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/genética , Penetrância , Mutação em Linhagem Germinativa , Caderinas/genética , Predisposição Genética para DoençaRESUMO
Data on preimplantation genetic testing (PGT-M) in patients with genetic susceptibility to cancer are scarce in the literature, while there is, in our experience, a growing familiarity with assisted reproduction techniques (ART) among pathogenic variant heterozygotes. We performed a retrospective multicenter study of PGT-M outcomes among French patients with genetic susceptibility to cancer. Our objectives were to collect data on this complex issue, and to help cancer geneticists counsel their patients of reproductive age. We also wanted to increase awareness regarding PGT-M among cancer genetics professionals. Patients from three university hospital cancer genetics clinics who had requested PGT-M between 2000 and 2019 were included retrospectively. Data were extracted from medical records. Patients were then contacted directly to collect missing and up-to-date information. Out of 41 eligible patients, 28 agreed explicitly to participate when contacted and were therefore included. They carried PV in VHL (n = 9), APC (n = 8), CDH1 (n = 5), STK11 (n = 2), AXIN2, BRCA1, MEN1, and FH (n = 1). Seven patients were denied PGT-M based on multidisciplinary team meetings or subsequently by the ART hospital teams, two changed their minds, and two were yet to start the process. PGT-M was successful in seven patients (25%), with a mean age at PGT-M request of 27. Most had von Hippel-Lindau. PGT-M failed in the remaining ten, with a mean age at PGT-M request of 32. The main reason for failure was non-implantation of the embryo. Of these, four patients were pursuing PGT-M at the time of last contact. PGT-M outcomes in patients with cancer susceptibility syndromes were satisfactory. These patients should be informed about PGT-M more systematically, which would imply greater awareness among cancer genetics professionals regarding ART. Our series was not representative of cancer susceptibility syndromes in general; the predominance of cases with syndromes characterized by early-onset, highly penetrant disease is explained by the restrictive French guidelines.
Assuntos
Neoplasias , Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Predisposição Genética para Doença , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Transferência Embrionária/métodos , Testes Genéticos/métodos , Neoplasias/diagnóstico , Neoplasias/genéticaRESUMO
Some patients with Lynch syndrome (LS) have extreme phenotypes, i.e. cancer before the recommended screening age, or cancer for which there are no screening guidelines. We made the hypothesis that additional germline variants in cancer susceptibility genes (CSG) could explain some of these phenotypes. We compared the prevalence of additional CSG variants in LS patients with a cancer diagnosis before age 30 (early-onset, EO group) and after 40 (usual-onset, UO group). While there was no overall difference, we did find an excess of pathogenic variants and variants of unknown significance in EO cases when only gastrointestinal CSG were considered (OR 2.25; 95% CI: 1.01-5.06, p value = 0.04). Four EO cases stood out: two with POLE/POLD1 variants in the key exonuclease domain, one with a BMPR1A duplication and one with an EPCAM deletion. Additional germline variants should be considered in future screening recommendations, as they might influence cancer risk.