Genetic and phenotypic characterization of families with familial pancreatic cancer and screening of high-risk individuals.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 242-242
Author(s):  
Carmen Guillen ◽  
Julie Earl ◽  
Evelina Mocci ◽  
Carme Guerrero ◽  
Jose Montans ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Screening Program ◽  
Premalignant Lesions ◽  
Phenotypic Characterization ◽  
Familial Pancreatic Cancer ◽  
Cystic Lesions ◽  
Term Survival ◽  
Clinical Screening ◽  
Partial Pancreatectomy

242 Background: The prognosis of patients diagnosed with Pancreatic Cancer (PC) is dismal with a 5-year survival rate of around 5%. Familial Pancreatic Cancer (FPC) is an autosomal dominant rare syndrome defined as families with two or more first-degree relatives with pancreatic cancer that do not fulfill the criteria of any other inherited tumor syndrome. The Spanish familial pancreatic cancer registry, Pan-Gen-FAM was established in 2009 in order to identify and manage families at high risk of developing PC. Methods: Information on the family history of cancer is collected in order to determine the phenotype of individual families and patients are offered genetic testing of known FPC associated genes pertinent to their familial syndrome. An individualized clinical screening program is devised for the early detection of a pancreatic tumor consisting of periodic monitoring by imaging techniques (EUS and MRI) and the evaluation of minimally-invasive tumor biomarkers approaches including Circulating Tumor Cells (CTC) and circulating free DNA in blood. Results: To date the registry includes 125 individuals representing some 41 families. Of 17 families tested so far BRCA2 germline mutations were detected in 5 families and a BRCA1 mutation in 1 family. 43 individuals underwent clinical screening. More pancreatic abnormalities were found by EUS (41%) than by MRI (31%). The most frequent abnormal findings were parenchymal changes associated with chronic pancreatitis. Eight cystic lesions were identified. One lesion was identified as a well differentiated neuroendocrine tumor and another was shown to have benign cytology and whilst carcinoma was found in a third patient, this patient underwent a subsequent partial pancreatectomy. The remaining patients with cystic lesions are undergoing close clinical observation. Seventy three patients underwent CTC determinations and all patients tested negative. Conclusions: Periodic screening of high risk individuals by EUS and RMI can detect small tumors and premalignant lesions. We hypothesize that these persons will have a higher probability of long-term survival than sporadic cases.

Spanish national hereditary pancreatic cancer registry (PanFAM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12033-e12033
Author(s):  
Carmen Guillen-Ponce ◽  
Evelina Mocci ◽  
Julie Earl ◽  
Carmen T Guerrero ◽  
Maria Celia Calcedo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Screening Program ◽  
Epidemiological Data ◽  
Screening Methods ◽  
Familial Pancreatic Cancer ◽  
Inherited Predisposition ◽  
Screening Study ◽  
Age Of Diagnosis ◽  
Breast And Prostate Cancer

e12033 Background: Inherited predisposition to Pancreatic Cancer (PC) corresponds 10% of all cases and includes members of families affected with hereditary cancer syndromes as Familial Pancreatic Cancer (FPC), Peutz-Jeghers, familial melanoma, hereditary breast and ovarian cancer, hereditary pancreatitis. An inherited predisposition in early onset PC (≤ 50 years) has also been suggested. We report preliminary data on PanFAM patients and screening of high risk individuals. Methods: PamFAM is a part of the European PANGEN PC case/control study of hereditary PC, co-ordinated by the Ramón y Cajal (RC) hospital and the Spanish National Cancer Research Center, with 16 participating hospitals. All families with clinical evidence of an inherited PC syndrome were recruited and multi-generational pedigrees were constructed. Cancer diagnoses were confirmed, when possible, by review of medical records. Blood samples and epidemiological data were collected for all participating family members. A screening program for early detection of PC, based on endoscopic ultrasound (EUS), CT and circulating tumour cells (CTCs) was offered to high risk individuals. Results: Of 505 Spanish PCs collected by PANGEN, 31 (~6%) were FPC cases; 18 (58%) revealed only PC and the remaining showed clustering with other tumor types, gastric cancer was the most common (13%). Among FPC families, 3 had 3 cases of PC and the remaining had 2 cases. The mean age of diagnosis was 67 years (range 47-85), 20 male and 11 female. Four FPCs were previously diagnosed with cancer (Hodgkin lymphoma, breast and prostate cancer) and 3 with acute pancreatitis. 37 PCs with no family history of cancer were diagnosed at the age of 50 years or earlier (mean 45, range 30-50), 18 male and 19 female. Other 27 eligible families were recruited by RyC hospital, 8 (30%) with FPC and 3 (11%) with PC ≤ 50 years. A cohort of 61 high risk individuals participes in the screening study: 3 had abnormal EUS, 1 a benign pancreatic node and 1 a renal angiolipoma; one young man had 2 CTCs. Conclusions: PanFAM is the first registry in Spain collecting hereditary PC cases and it represents an important resource to identify underlying gene defects and to the development of screening methods precursor lesions detection in high risk individuals.

Spanish registry and screening program for families at high risk of pancreatic adenocarcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 192-192
Author(s):  
Carmen Guillen-Ponce ◽  
Evelina Mocci ◽  
Mirari Marquez ◽  
Julie Earl ◽  
Carmen T Guerrero ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
High Risk ◽  
Screening Program ◽  
Familial Aggregation ◽  
Molecular Characteristics ◽  
High Risk Population ◽  
Familial Pancreatic Cancer ◽  
Preneoplastic Lesions ◽  
History Of

192 Background: 5-10% of pancreatic cancer (PC) cases show familial aggregation. 20% of these correspond to syndromes: Peutz Jeghers, hereditary pancreatitis, familial multiple melanoma, breast and ovarian cancer (HBOC) and others. Familial pancreatic cancer (FPC) is defined as: ≥2 first degree relatives with PC and with no other known syndromes. FPC seems to have autosomal dominant inheritance, but the genetic cause is unknown. Methods: The objectives are: 1) To develop the first FPC Spanish Registry, connecting different groups interested in this disease 2) To study inheritance, phenotypic and molecular characteristics of the FPC, and families with early PC 3) To establish a strategy for early detection of PC in high-risk individuals and to implement it 4) To characterize preneoplastic lesions and diagnosed PC by monitoring high-risk individuals. 16 Spanish hospitals are participating. This study has two components: 1) Cohort to identify families with FPC and hereditary PC. Sources for the families are the PanGen-ES Study, a case-control study of PC which identifies families through a questionnaire on family history of cancer, and Genetic Counseling Units, 2) Cohort of high-risk families. The latter will be followed up by endoscopic ultrasound (EUS) and CT ± abdominal magnetic resonance imaging. In addition, circulating tumor cells (CTC) in peripheral blood will be determined. Results: The assessment of family history of the 421 cases included in the PanGen Study has identified 32 (7.6%) families with FPC and 52 patients with PC ≤ 50 years (12.4%). In addition, the 190 families presenting PC aggregation with other neoplasms are being further evaluated. At this time we have obtained clinical data and blood samples to carry out molecular studies of 23 individuals: 17 belonging to 3 families with FPC, and 6 members of 2 families with an HBOC with some cases of pancreatic cancer. 18 relatives at risk began a follow-up with EUS and CT, with no detection of any suspicious pancreatic lesion; also CTC have not been detected. Conclusions: This initiative will permit to know more about FPC and will serve to evaluate protocols and PC markers in screening the high-risk population, and promote connections with other international groups.

Risk independence for the identification of cystic lesions in Familial Pancreatic Cancer (FPC) kindreds

Pancreatology ◽  
2017 ◽  
Vol 17 (3) ◽  
pp. S68
Author(s):  
Andrea Sheel ◽  
Sara Harrison ◽  
Ioannis Sarantitis ◽  
James Nicholson ◽  
Christopher Halloran ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Familial Pancreatic Cancer ◽  
Cystic Lesions

The Spanish familial pancreatic cancer registry panfam: Screening of high-risk individuals

Pancreatology ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. S126
Author(s):  
Carmen Guillèn-Ponce ◽  
Julie Earl ◽  
Maria Teresa Salazar Lopez ◽  
Celia Calcedo ◽  
Reyes Ferreiro ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Cancer Registry ◽  
Familial Pancreatic Cancer

scholarly journals Genetic counselling and personalised risk assessment in the Australian pancreatic cancer screening program

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Tanya Dwarte ◽  
Skye McKay ◽  
Amber Johns ◽  
Katherine Tucker ◽  
Allan D. Spigelman ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pancreatic Cancer ◽  
Genetic Testing ◽  
High Risk ◽  
Genetic Counselling ◽  
Screening Program ◽  
Pathogenic Variant ◽  
Recruitment Strategy ◽  
Close Relative

Abstract Background Pancreatic cancer (PC) is an aggressive disease with a dismal 5-year survival rate. Surveillance of high-risk individuals is hoped to improve survival outcomes by detection of precursor lesions or early-stage malignancy. Methods Since 2011, a national high-risk cohort recruited through St Vincent’s Hospital, Sydney, has undergone prospective PC screening incorporating annual endoscopic ultrasound, formal genetic counselling and mutation analysis as appropriate. PancPRO, a Bayesian PC risk assessment model, was used to estimate 5-year and lifetime PC risks for familial pancreatic cancer (FPC) participants and this was compared to their perceived chance of pancreatic and other cancers. Genetic counselling guidelines were developed to improve consistency. Follow-up questionnaires were used to assess the role of genetic counselling and testing. Results We describe the Australian PC screening program design and recruitment strategy and the results of the first 102 individuals who have completed at least one-year of follow-up. Seventy-nine participants met the FPC criteria (≥ two first-degree relatives affected), 22 individuals had both a BRCA2 pathogenic variant and a close relative with PC and one had a clinical diagnosis of Peutz-Jeghers syndrome. Participants reported a high perceived chance of developing PC regardless of their genetic testing status. PancPRO reported FPC participants’ mean 5-year and lifetime PC risks as 1.81% (range 0.2–3.2%) and 10.17% (range 2.4–14.4%), respectively. Participants’ perceived PC chance did not correlate with their PancPRO 5-year (r = − 0.17, p = 0.128) and lifetime PC risks (r = 0.19, p = 0.091). Two-thirds felt that current genetic testing would help them, and 91% of tested participants were glad to have undergone genetic testing. Overall, 79% of participants found genetic counselling to be helpful, and 88% reported they would recommend counselling to their relatives. Conclusions Participants reported multiple benefits of genetic counselling and testing but continue to seek greater clarification about their individual PC risk. Extension of PancPRO is required to enable personalised PC risk assessment for all high-risk sub-groups. More detailed discussion of PC risk for BRCA2 pathogenic variant carriers, providing a written summary in all cases and a plan for genetics review were identified as areas for improvement.

scholarly journals PancPRO: Risk Assessment for Individuals With a Family History of Pancreatic Cancer

2007 ◽  
Vol 25 (11) ◽  
pp. 1417-1422 ◽  
Author(s):  
Wenyi Wang ◽  
Sining Chen ◽  
Kieran A. Brune ◽  
Ralph H. Hruban ◽  
Giovanni Parmigiani ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pancreatic Cancer ◽  
Family History ◽  
High Risk ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Familial Pancreatic Cancer ◽  
Cancer Susceptibility Gene

Purpose The rapid fatality of pancreatic cancer is, in large part, the result of an advanced stage of diagnosis for the majority of patients. Identification of individuals at high risk of developing pancreatic cancer is a first step towards the early detection of this disease. Individuals who may harbor a major pancreatic cancer susceptibility gene are one such high-risk group. The goal of this study was to develop and validate PancPRO, a Mendelian model for pancreatic cancer risk prediction in individuals with familial pancreatic cancer, to identify high-risk individuals. Methods PancPRO was built by extending the Bayesian modeling framework developed for BRCAPRO, trained using published data, and validated using independent prospective data on 961 families enrolled onto the National Familial Pancreas Tumor Registry, including 26 individuals who developed incident pancreatic cancer during follow-up. Results We developed a risk prediction model, PancPRO, and free software for the estimation of pancreatic cancer susceptibility gene carrier probabilities and absolute pancreatic cancer risk. Model validation demonstrated an observed to predicted pancreatic cancer ratio of 0.83 (95% CI, 0.52 to 1.20) and high discriminatory ability, with an area under the receiver operating characteristic curve of 0.75 (95% CI, 0.68 to 0.81) for PancPRO. Conclusion PancPRO is the first risk prediction model for pancreatic cancer. When we validated our model using the largest registry of familial pancreatic cancer, our model provided accurate risk assessment. Our findings highlight the importance of detailed family history for clinical cancer risk assessment and demonstrate that accurate genetic risk assessment is possible even when the causative genes are not known.

The Spanish national familial pancreatic cancer registry Pan-Gen-FAM: Screening of high-risk individuals for the early detection of a pancreatic tumor

Pancreatology ◽  
2016 ◽  
Vol 16 (3) ◽  
pp. S87
Author(s):  
Carmen Guillén-Ponce ◽  
Reyes Ferreiro ◽  
Vanessa Pachon ◽  
Julie Earl ◽  
Maria Teresa Salazar Lopez ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Early Detection ◽  
Cancer Registry ◽  
Pancreatic Tumor ◽  
Familial Pancreatic Cancer
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