期刊
CANCERS
卷 14, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/cancers14184447
关键词
pancreatic cancer; genetics; DNA Damage Repair-Homologous Recombination Deficiency (DDR-HRD); hereditary cancer syndromes; germline; multigene panel testing; BRCA; CDKN2A; overall survival
类别
资金
- Lega Italiana per la Lotta contro i Tumori (LILT)
- Italian Ministry of Health (Ospedale Policlinico San Martino Ricerca Corrente)
- Associazione Ricerca Tumori Rari ed Ereditari (AR3) onlus
This study investigated the prevalence and impact of pathogenic variants in 51 susceptibility genes in Italian pancreatic cancer patients. The results showed that 17% of patients carried pathogenic variants, with CDKN2A being the most common. Carriers of pathogenic variants had better survival rates, and a portion of them had no family history. CDKN2A and ATM should be included in testing for BRCA1/2 regardless of family history in the Italian population.
Simple Summary Multigene germline panel testing data, extended beyond BRCA, in unselected pancreatic cancer patients, are missing in the Italian population. We aimed here to determine the prevalence and impact of pathogenic variants in 51 pancreatic cancer candidate susceptibility genes in an unselected cohort of Italian pancreatic cancer patients. We found that 17% were carriers. CDKN2A was the most frequently mutated gene, followed by BRCA2 and ATM. Carriers showed better overall survival. A total of 41% of them had no family history. All CDKN2A carriers were older than 50 years, and BRCA1/2 carriers were younger than 70 years. CDKN2A and ATM should be added to current BRCA1/2 testing independently of family history in our population. Multigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-BRCA1/2 genes, the clinical utility is unclear. A comprehensive multi-gene assessment in unselected Italian PC patients is missing. We evaluated the prevalence and impact of Pathogenic Variants (PV) in 51 PC susceptibility genes in a real-world series of 422 Italian PC patients unselected for Family History (FH), compared the clinical characteristics and conducted survival analyses. 17% of patients had PVs (70/422), mainly in BRCA1/2 (4.5%, all <70 y), CDKN2A (4.5%, all >50 y), ATM (2.1%). PV carriers were younger (64 vs. 67; p = 0.02) and had more frequent personal/FH of PC, melanoma and breast/ovarian cancer (all p < 0.05). The Overall Survival (OS) was longer in patients carrying PVs (HR 0.78; p = 0.090), comprising ATM carriers (HR 0.33; p = 0.054). In the oxaliplatin-treated subset, PV carriers showed better control of the disease, although this was not statistically significant (67% vs. 56%). CDKN2A, BRCA2 and ATM were the most frequently altered genes. ATM PVs were positively associated with OS in 41% of PV carriers, 60% of whom carried CDKN2A, BRCA2 or ATM PVs, had negative FH and would have been missed by traditional referral. Thus, CDKN2A and ATM should be added to BRCA1/2 testing regardless of FH.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据