Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients

Multigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-<i>BRCA1/2</i> 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 Patho...

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Main Authors: Alberto Puccini, Marta Ponzano, Bruna Dalmasso, Irene Vanni, Annalice Gandini, Silvia Puglisi, Roberto Borea, Malvina Cremante, William Bruno, Virginia Andreotti, Eleonora Allavena, Valentino Martelli, Fabio Catalano, Massimiliano Grassi, Maria Laura Iaia, Chiara Pirrone, Alessandro Pastorino, Giuseppe Fornarini, Stefania Sciallero, Paola Ghiorzo, Lorenza Pastorino
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/14/18/4447
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Summary:Multigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-<i>BRCA1/2</i> 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 <i>BRCA1/2</i> (4.5%, all <70 y), <i>CDKN2A</i> (4.5%, all >50 y), ATM (2.1%). PV carriers were younger (64 vs. 67; <i>p</i> = 0.02) and had more frequent personal/FH of PC, melanoma and breast/ovarian cancer (all <i>p</i> < 0.05). The Overall Survival (OS) was longer in patients carrying PVs (HR 0.78; <i>p</i> = 0.090), comprising <i>ATM</i> carriers (HR 0.33; <i>p</i> = 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. <i>ATM</i> PVs were positively associated with OS in 41% of PV carriers, 60% of whom carried <i>CDKN2A,</i><i>BRCA2</i> or <i>ATM</i> PVs, had negative FH and would have been missed by traditional referral. Thus, <i>CDKN2A</i> and <i>ATM</i> should be added to <i>BRCA1/2</i> testing regardless of FH.
ISSN:2072-6694