Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/27305
Title: Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants.
Austin Authors: Murali, Krithika;Dwarte, Tanya M;Nikfarjam, Mehrdad ;Tucker, Katherine M;Vaughan, Rhys B ;Efthymiou, Marios ;Collins, Allison L ;Spigelman, Allan D;Salmon, Lucinda ;Johns, Amber L;Williams, David B;Delatycki, Martin B ;John, Thomas ;Stoita, Alina
Affiliation: Olivia Newton-John Cancer Wellness and Research Centre
Gastroenterology and Hepatology
Surgery
Cancer Genetics Unit, The Kinghorn Cancer Centre, St Vincent's Hospital, Darlinghurst, NSW, 2010, Australia
University of New South Wales, Prince of Wales Clinical School, Randwick, NSW, 2031, Australia
Hereditary Cancer Centre, Prince of Wales Hospital, Randwick, NSW, 2031, Australia
Peter MacCallum Cancer Centre, Parkville, VIC, 3000, Australia
Department of Gastroenterology, St Vincent's Hospital, Darlinghurst, NSW, 2010, Australia
Australian Pancreatic Cancer Genome Initiative, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia
Clinical Genetics
Issue Date: 16-Aug-2021
Date: 2021
Publication information: Hereditary Cancer in Clinical Practice 2021; 19(1): 33
Abstract: The Australian Pancreatic Cancer Screening Program (APCSP) offers endoscopic ultrasound surveillance for individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) with all participants requiring assessment by a Familial Cancer Service before or after study enrolment. Individuals aged 40-80 years (or 10 years younger than the earliest PDAC diagnosis) were eligible for APCSP study entry if they had 1) ≥ two blood relatives with PDAC (at least one of first-degree association); 2) a clinical or genetic diagnosis of Hereditary Pancreatitis or Peutz-Jeghers syndrome irrespective of PDAC family history; or 3) a known PDAC predisposition germline pathogenic variant (BRCA2, PALB2, CDKN2A, or Lynch syndrome) with ≥one PDAC-affected first- or second-degree relative. Retrospective medical record review was conducted for APCSP participants enrolled at the participating Australian hospitals from January 2011 to December 2019. We audited the genetic investigations offered by multiple Familial Cancer Services who assessed APCSP participants according to national guidelines, local clinical protocol and/or the availability of external research-funded testing, and the subsequent findings. Descriptive statistical analysis was performed using Microsoft Excel. Of 189 kindreds (285 participants), 50 kindreds (71 participants) had a known germline pathogenic variant at enrolment (BRCA2 n = 35, PALB2 n = 6, CDKN2A n = 3, STK11 n = 3, PRSS1 n = 2, MLH1 n = 1). Forty-eight of 136 (35%) kindreds with no known germline pathogenic variant were offered mutation analysis; 89% was clinic-funded, with increasing self-funded testing since 2016. The relatively low rates of genetic testing performed reflects initial strict criteria for clinic-funded genetic testing. New germline pathogenic variants were detected in five kindreds (10.4%) after study enrolment (BRCA2 n = 3 kindreds, PALB2 n = 1, CDKN2A n = 1). Of note, only eight kindreds were reassessed by a Familial Cancer Service since enrolment, with a further 21 kindreds identified as being suitable for reassessment. Germline pathogenic variants associated with PDAC were seen in 29.1% of our high-risk cohort (55/189 kindreds; 82/285 participants). Importantly, 10.4% of kindreds offered genetic testing were newly identified as having germline pathogenic variants, with majority being BRCA2. As genetic testing standards evolve rapidly in PDAC, 5-yearly reassessment of high-risk individuals by Familial Cancer Services is warranted.
URI: https://ahro.austin.org.au/austinjspui/handle/1/27305
DOI: 10.1186/s13053-021-00190-1
ORCID: 0000-0001-5581-2039
0000-0003-0918-7820
0000-0003-4866-276X
0000-0002-7180-6576
0000-0002-4557-1734
0000-0003-2569-5163
0000-0002-7362-4637
0000-0002-7409-1684
0000-0001-8550-0829
0000-0002-1948-6683
0000-0002-0808-0311
0000-0002-8769-2569
0000-0003-3399-5342
0000-0001-9460-2149
Journal: Hereditary Cancer in Clinical Practice
PubMed URL: 34399810
ISSN: 1731-2302
Type: Journal Article
Subjects: Cancer screening
Genetic testing
Genetics
Hereditary Cancer syndromes
Pancreatic cancer
Pathogenic variant
Appears in Collections:Journal articles

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