Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients. Orsi, G., Carconi, C., Ghiorzo, P., Carrera, P., Pastorino, L., Presi, S., Chiaravalli, M., Barbieri, E., Giordano, G., Sciallero, S., Puccini, A., Salvatore, L., Cortesi, L., Macchini, M., Natalicchio, M. I., Allavena, E., Pirrone, C., Archibugi, L., Dalmasso, B., Bruno, W., Tortora, G., Landriscina, M., Capurso, G., Cascinu, S., Falconi, M., & Reni, M. European Journal of Cancer, 208:114226, July, 2024. ![Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Background and aim Germline BRCA1–2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients. Methods Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A. Results 11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1–2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged \textgreater 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients. Conclusions A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1–2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.
@article{orsi_germline_2024,
title = {Germline pathogenic variants of cancer predisposition genes in a multicentre {Italian} cohort of pancreatic cancer patients.},
volume = {208},
issn = {0959-8049},
url = {https://www.sciencedirect.com/science/article/pii/S0959804924008827},
doi = {10.1016/j.ejca.2024.114226},
abstract = {Background and aim
Germline BRCA1–2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.
Methods
Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A.
Results
11.5 \% (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 \%), BRCA2 (2.9 \%), BRCA1 (1.6 \%), CHEK2 (1.1 \%). Patients harboring any CP-18 gene and BRCA1–2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 \% in all subgroups of patients, including those aged {\textgreater} 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 \% (23/869) of patients.
Conclusions
A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1–2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.},
urldate = {2024-07-24},
journal = {European Journal of Cancer},
author = {Orsi, Giulia and Carconi, Catia and Ghiorzo, Paola and Carrera, Paola and Pastorino, Lorenza and Presi, Silvia and Chiaravalli, Marta and Barbieri, Elena and Giordano, Guido and Sciallero, Stefania and Puccini, Alberto and Salvatore, Lisa and Cortesi, Laura and Macchini, Marina and Natalicchio, Maria Iole and Allavena, Eleonora and Pirrone, Chiara and Archibugi, Livia and Dalmasso, Bruna and Bruno, William and Tortora, Giampaolo and Landriscina, Matteo and Capurso, Gabriele and Cascinu, Stefano and Falconi, Massimo and Reni, Michele},
month = jul,
year = {2024},
keywords = {ATM, BRCA, Cancer predisposition genes, DNA damage repair, Germline pathogenic variant, HCS, Hereditary Cancer Solution, Pancreatic cancer, SOPHiA DDM},
pages = {114226},
}
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{"_id":"gCCq4aFnMcB5Lk7rQ","bibbaseid":"orsi-carconi-ghiorzo-carrera-pastorino-presi-chiaravalli-barbieri-etal-germlinepathogenicvariantsofcancerpredispositiongenesinamulticentreitaliancohortofpancreaticcancerpatients-2024","author_short":["Orsi, G.","Carconi, C.","Ghiorzo, P.","Carrera, P.","Pastorino, L.","Presi, S.","Chiaravalli, M.","Barbieri, E.","Giordano, G.","Sciallero, S.","Puccini, A.","Salvatore, L.","Cortesi, L.","Macchini, M.","Natalicchio, M. I.","Allavena, E.","Pirrone, C.","Archibugi, L.","Dalmasso, B.","Bruno, W.","Tortora, G.","Landriscina, M.","Capurso, G.","Cascinu, S.","Falconi, M.","Reni, M."],"bibdata":{"bibtype":"article","type":"article","title":"Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.","volume":"208","issn":"0959-8049","url":"https://www.sciencedirect.com/science/article/pii/S0959804924008827","doi":"10.1016/j.ejca.2024.114226","abstract":"Background and aim Germline BRCA1–2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients. Methods Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A. Results 11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1–2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged \\textgreater 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients. Conclusions A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1–2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.","urldate":"2024-07-24","journal":"European Journal of Cancer","author":[{"propositions":[],"lastnames":["Orsi"],"firstnames":["Giulia"],"suffixes":[]},{"propositions":[],"lastnames":["Carconi"],"firstnames":["Catia"],"suffixes":[]},{"propositions":[],"lastnames":["Ghiorzo"],"firstnames":["Paola"],"suffixes":[]},{"propositions":[],"lastnames":["Carrera"],"firstnames":["Paola"],"suffixes":[]},{"propositions":[],"lastnames":["Pastorino"],"firstnames":["Lorenza"],"suffixes":[]},{"propositions":[],"lastnames":["Presi"],"firstnames":["Silvia"],"suffixes":[]},{"propositions":[],"lastnames":["Chiaravalli"],"firstnames":["Marta"],"suffixes":[]},{"propositions":[],"lastnames":["Barbieri"],"firstnames":["Elena"],"suffixes":[]},{"propositions":[],"lastnames":["Giordano"],"firstnames":["Guido"],"suffixes":[]},{"propositions":[],"lastnames":["Sciallero"],"firstnames":["Stefania"],"suffixes":[]},{"propositions":[],"lastnames":["Puccini"],"firstnames":["Alberto"],"suffixes":[]},{"propositions":[],"lastnames":["Salvatore"],"firstnames":["Lisa"],"suffixes":[]},{"propositions":[],"lastnames":["Cortesi"],"firstnames":["Laura"],"suffixes":[]},{"propositions":[],"lastnames":["Macchini"],"firstnames":["Marina"],"suffixes":[]},{"propositions":[],"lastnames":["Natalicchio"],"firstnames":["Maria","Iole"],"suffixes":[]},{"propositions":[],"lastnames":["Allavena"],"firstnames":["Eleonora"],"suffixes":[]},{"propositions":[],"lastnames":["Pirrone"],"firstnames":["Chiara"],"suffixes":[]},{"propositions":[],"lastnames":["Archibugi"],"firstnames":["Livia"],"suffixes":[]},{"propositions":[],"lastnames":["Dalmasso"],"firstnames":["Bruna"],"suffixes":[]},{"propositions":[],"lastnames":["Bruno"],"firstnames":["William"],"suffixes":[]},{"propositions":[],"lastnames":["Tortora"],"firstnames":["Giampaolo"],"suffixes":[]},{"propositions":[],"lastnames":["Landriscina"],"firstnames":["Matteo"],"suffixes":[]},{"propositions":[],"lastnames":["Capurso"],"firstnames":["Gabriele"],"suffixes":[]},{"propositions":[],"lastnames":["Cascinu"],"firstnames":["Stefano"],"suffixes":[]},{"propositions":[],"lastnames":["Falconi"],"firstnames":["Massimo"],"suffixes":[]},{"propositions":[],"lastnames":["Reni"],"firstnames":["Michele"],"suffixes":[]}],"month":"July","year":"2024","keywords":"ATM, BRCA, Cancer predisposition genes, DNA damage repair, Germline pathogenic variant, HCS, Hereditary Cancer Solution, Pancreatic cancer, SOPHiA DDM","pages":"114226","bibtex":"@article{orsi_germline_2024,\n\ttitle = {Germline pathogenic variants of cancer predisposition genes in a multicentre {Italian} cohort of pancreatic cancer patients.},\n\tvolume = {208},\n\tissn = {0959-8049},\n\turl = {https://www.sciencedirect.com/science/article/pii/S0959804924008827},\n\tdoi = {10.1016/j.ejca.2024.114226},\n\tabstract = {Background and aim\nGermline BRCA1–2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.\nMethods\nClinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A.\nResults\n11.5 \\% (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 \\%), BRCA2 (2.9 \\%), BRCA1 (1.6 \\%), CHEK2 (1.1 \\%). Patients harboring any CP-18 gene and BRCA1–2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 \\% in all subgroups of patients, including those aged {\\textgreater} 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 \\% (23/869) of patients.\nConclusions\nA remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1–2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.},\n\turldate = {2024-07-24},\n\tjournal = {European Journal of Cancer},\n\tauthor = {Orsi, Giulia and Carconi, Catia and Ghiorzo, Paola and Carrera, Paola and Pastorino, Lorenza and Presi, Silvia and Chiaravalli, Marta and Barbieri, Elena and Giordano, Guido and Sciallero, Stefania and Puccini, Alberto and Salvatore, Lisa and Cortesi, Laura and Macchini, Marina and Natalicchio, Maria Iole and Allavena, Eleonora and Pirrone, Chiara and Archibugi, Livia and Dalmasso, Bruna and Bruno, William and Tortora, Giampaolo and Landriscina, Matteo and Capurso, Gabriele and Cascinu, Stefano and Falconi, Massimo and Reni, Michele},\n\tmonth = jul,\n\tyear = {2024},\n\tkeywords = {ATM, BRCA, Cancer predisposition genes, DNA damage repair, Germline pathogenic variant, HCS, Hereditary Cancer Solution, Pancreatic cancer, SOPHiA DDM},\n\tpages = {114226},\n}\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n","author_short":["Orsi, G.","Carconi, C.","Ghiorzo, P.","Carrera, P.","Pastorino, L.","Presi, S.","Chiaravalli, M.","Barbieri, E.","Giordano, G.","Sciallero, S.","Puccini, A.","Salvatore, L.","Cortesi, L.","Macchini, M.","Natalicchio, M. 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