Familial Pancreatic Cancer

Benzel, Julia; Fendrich, Volker

doi:10.1159/000493473

Cited by 39 publications

(34 citation statements)

References 111 publications

(196 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, medium-and high-risk groups can be considered suitable for screening, including some genetic mutations that cause, for example, hereditary chronic pancreatitis [15,16] and a number of other tumor syndromes (Peutz-Jeghers syndrome, hereditary non-polyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), familial atypical multiple mole melanoma syndrome (FAMMM syndrome) [17][18][19][20]. Risk groups also include persons with familial PC, which is defined as the occurrence of PC in at least two or more firstdegree relatives [21,22]. In some meta-analyzes, the presence of Helicobacter pylori appears to slightly increase the risk of developing PC [23,24].…”

Section: Screening and Diagnostics Of Pcmentioning

confidence: 99%

Risk factors of pancreatic cancer and their possible uses in diagnostics

J¹,

Kunovský²,

Kala³

et al. 2021

neo

View full text Add to dashboard Cite

Section: Screening and Diagnostics Of Pcmentioning

confidence: 99%

Risk factors of pancreatic cancer and their possible uses in diagnostics

J¹,

Kunovský²,

Kala³

et al. 2021

neo

View full text Add to dashboard Cite

“…BRCA1 or BRCA2 germline mutations reportedly increase the relative risk of pancreatic cancer by 2.26-fold (1.26−4.06) and 3.51-fold (1.87−6.58), respectively [36,37]. It has been reported that 25% of the patients with BRCA1/2 gene germline mutations are at risk of developing pancreatic cancer, and the lifetime risk of developing pancreatic cancer in patients with BRCA1/2 gene germline mutations is estimated to be 3-8% [39][40][41][42]. Additionally, germline or somatic BRCA1/2 mutations are associated with 5−9% of the unselected cases of pancreatic cancer [21,43,44].…”

Section: Target Therapy For Germline Mutationmentioning

confidence: 99%

Tumour-Agnostic Therapy for Pancreatic Cancer and Biliary Tract Cancer

Kato

2021

Diagnostics

View full text Add to dashboard Cite

The prognosis of patients with solid tumours has remarkably improved with the development of molecular-targeted drugs and immune checkpoint inhibitors. However, the improvements in the prognosis of pancreatic cancer and biliary tract cancer is delayed compared to other carcinomas, and the 5-year survival rates of distal-stage disease are approximately 10 and 20%, respectively. However, a comprehensive analysis of tumour cells using The Cancer Genome Atlas (TCGA) project has led to the identification of various driver mutations. Evidently, few mutations exist across organs, and basket trials targeting driver mutations regardless of the primary organ are being actively conducted. Such basket trials not only focus on the gate keeper-type oncogene mutations, such as HER2 and BRAF, but also focus on the caretaker-type tumour suppressor genes, such as BRCA1/2, mismatch repair-related genes, which cause hereditary cancer syndrome. As oncogene panel testing is a vital approach in routine practice, clinicians should devise a strategy for improved understanding of the cancer genome. Here, the gene mutation profiles of pancreatic cancer and biliary tract cancer have been outlined and the current status of tumour-agnostic therapy in these cancers has been reported.

show abstract

“…One of the challenges in early detection of PDAC is the selection of the appropriate cohorts at risk, as screening in the general population is not feasible [62,63]. Currently guidelines recommend screening of asymptomatic individuals with a history of FPC and predisposing genetic syndromes [64]. Additional amenable cohorts include patients with CP, cystic lesions of the pancreas, and new onset diabetes (NOD) [62].…”

Section: Plos Medicinementioning

confidence: 99%

A combination of urinary biomarker panel and PancRISK score for earlier detection of pancreatic cancer: A case–control study

et al. 2020

View full text Add to dashboard Cite

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with around 9% of patients surviving >5 years. Asymptomatic in its initial stages, PDAC is mostly diagnosed late, when already a locally advanced or metastatic disease, as there are no useful biomarkers for detection in its early stages, when surgery can be curative. We have previously described a promising biomarker panel (LYVE1, REG1A, and TFF1) for earlier detection of PDAC in urine. Here, we aimed to establish the accuracy of an improved panel, including REG1B instead of REG1A, and an algorithm for data interpretation, the PancRISK score, in additional retrospectively collected urine specimens. We also assessed the complementarity of this panel with CA19-9 and explored the daily variation and stability of the biomarkers and their performance in common urinary tract cancers. Methods and findings Clinical specimens were obtained from multiple centres: Barts Pancreas Tissue Bank, University College London, University of Liverpool, Spanish National Cancer Research Center, Cambridge University Hospital, and University of Belgrade. The biomarker panel was assayed on 590 urine specimens: 183 control samples, 208 benign hepatobiliary disease samples (of which 119 were chronic pancreatitis), and 199 PDAC samples (102 stage I–II and 97 stage III–IV); 50.7% were from female individuals. PDAC samples were collected from patients before treatment. The samples were assayed using commercially available ELISAs. Statistical analyses were performed using non-parametric Kruskal–Wallis tests adjusted for multiple comparisons, and multiple logistic regression. Training and validation datasets for controls and PDAC samples were obtained after random division of the whole available dataset in a 1:1 ratio. The substitution of REG1A with REG1B enhanced the performance of the panel to detect resectable PDAC. In a comparison of controls and PDAC stage I–II samples, the areas under the receiver operating characteristic curve (AUCs) increased from 0.900 (95% CI 0.843–0.957) and 0.926 (95% CI 0.843–1.000) in the training (50% of the dataset) and validation sets, respectively, to 0.936 in both the training (95% CI 0.903–0.969) and the validation (95% CI 0.888–0.984) datasets for the new panel including REG1B. This improved panel showed both sensitivity (SN) and specificity (SP) to be >85%. Plasma CA19-9 enhanced the performance of this panel in discriminating PDAC I–II patients from controls, with AUC = 0.992 (95% CI 0.983–1.000), SN = 0.963 (95% CI 0.913–1.000), and SP = 0.967 (95% CI 0.924–1.000). We demonstrate that the biomarkers do not show significant daily variation, and that they are stable for up to 5 days at room temperature. The main limitation of our study is the low number of stage I–IIA PDAC samples (n = 27) and lack of samples from individuals with hereditary predisposition to PDAC, for which specimens collected from control individuals were used as a proxy. Conclusions We have successfully validated our urinary biomarker panel, which was improved by substituting REG1A with REG1B. At a pre-selected cutoff of >80% SN and SP for the affiliated PancRISK score, we demonstrate a clinically applicable risk stratification tool with a binary output for risk of developing PDAC (‘elevated’ or ‘normal’). PancRISK provides a step towards precision surveillance for PDAC patients, which we will test in a prospective clinical study, UroPanc.

show abstract

Familial Pancreatic Cancer

Cited by 39 publications

References 111 publications

Risk factors of pancreatic cancer and their possible uses in diagnostics

Risk factors of pancreatic cancer and their possible uses in diagnostics

Tumour-Agnostic Therapy for Pancreatic Cancer and Biliary Tract Cancer

A combination of urinary biomarker panel and PancRISK score for earlier detection of pancreatic cancer: A case–control study

Contact Info

Product

Resources

About