Identification of hereditary factors influencing the formation of a pancreatic carcinoma and other solid tumours
| Autor: | Král, Jan |
|---|---|
| Přispěvatelé: | Janatová, Markéta, Hojný, Jan, Šeborová, Karolína |
| Jazyk: | čeština |
| Rok vydání: | 2023 |
| Předmět: |
germline mutation
hereditární nádorová predispozice sekvenování nové generace next-generation sequencing pancreatic ductal adenocarcinoma panelové sekvenování duktální adenokarcinom pankreatu hereditary predisposition to cancer endometrial cancer karcinom endometria panel sequencing zárodečné mutace |
| Popis: | Pancreatic adenocarcinoma (PDAC) has one of the worst prognoses out of all cancers worldwide. Endometrial carcinoma (EC) is the most common gynecological cancer. Genetic background of tumors is highly heterogenous and differs among populations. We have analyzed DNA of 226 PDAC patients and 527 EC patients using panel next- generation sequencing. Targeted genes were divided into main predisposition genes (11 for PDAC, 19 for EC) and other candidate genes. EC patients were categorized based on meeting the indication criteria for germline genetic testing. Two sets of population-matched controls were used (controls with negative cancer history, and general population controls). Germline pathogenic variants (PV) in main predisposition genes were identified in 18 (8.0%) PDAC patients. The most mutated gene was BRCA2 (50% of carriers). PDAC risk was significantly elevated in carriers of PV in BRCA1 (OR = 10.4, p = 0.04), BRCA2 (OR = 6.4, p = 0.0009), and CHEK2 (OR = 17.5, p = 0.003). Germline mutations in genes participating in homologous recombination processes were associated with improved overall survival of patients. Among EC patients there were 60 (11.4%) carriers of PV in main predisposition genes. Carriers of PV in Lynch syndrome (LS) genes had markedly elevated risk of developing EC (OR = 22.4, p... |
| Databáze: | OpenAIRE |
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