Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance

• Published in: Journal of medical genetics Vol. 50; no. 1; pp. 59 - 64
• Main Authors: Korsse, Susanne E, Harinck, Femme, van Lier, Margot G F, Biermann, Katharina, Offerhaus, G Johan A, Krak, Nanda, Looman, Caspar W N, van Veelen, Wendy, Kuipers, Ernst J, Wagner, Anja, Dekker, Evelien, Mathus-Vliegen, Elisabeth M H, Fockens, Paul, van Leerdam, Monique E, Bruno, Marco J
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.01.2013; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adult; Age; ampullary cancer; Bile; Biological and medical sciences; Cohort Studies; Databases, Factual; distal bile duct cancer; Family medical history; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Genetics of eukaryotes. Biological and molecular evolution; Health risk assessment; Histology; Humans; inherited cancer syndrome; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical genetics; Medical prognosis; Medical records; Medical sciences; Middle Aged; Molecular and cellular biology; Mortality; Mutation; Netherlands - epidemiology; pancreactic cancer; Pancreatic cancer; Pancreatic Neoplasms - complications; Pancreatic Neoplasms - epidemiology; Peutz-Jeghers syndrome; Peutz-Jeghers Syndrome - complications; Peutz-Jeghers Syndrome - epidemiology; Population; Population Surveillance; Risk; Sociodemographics; Studies; Surveillance; Tumors; Young Adult; Netherlands; Human; Skin disease; Pigmentation disorder; Lentiginosis; Patient; Risk; Malignant tumor; Polyposis; Peutz-Jeghers syndrome; Genetic disease; Surveillance; Cohort study; Pancreas cancer; Risk factor; Digestive diseases; Genetics; Benign neoplasm; Cancer; Pancreatic disease
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmedgenet-2012-101277

Background Although Peutz-Jeghers syndrome (PJS) is known to be associated with pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We therefore aimed to determine the PC risk in a large cohort of Dutch PJS patients. Methods PJS was defined by diagnostic criteria recommended by the WHO, a proven LKB1 mutation, or both. All patients with a presumptive diagnosis of pancreatic, ampullary or distal bile duct cancer were identified. Cases were reviewed clinically, radiologically and immunohistochemically. Cumulative PC risks were calculated by Kaplan-Meier analysis and relative risks by Poisson regression analysis. Results We included 144 PJS patients (49% male) from 61 families (5640 person years follow-up). Seven (5%) patients developed PC at a median age of 54 years. Four patients (3%) were diagnosed with distal bile duct (n=2) or ampullary cancer (n=2) at a median age of 55 years. The cumulative risk for PC was 26% (95% CI 4% to 47%) at age 70 years and relative risk was 76 (95% CI 36 to 160; p<0.001). The cumulative risk for pancreatico-biliary cancer was 32% (95% CI 11% to 52%) at age 70 years, with a relative risk of 96 (95% CI 53 to 174; p<0.001). Conclusions PJS patients have a highly increased risk for pancreatico-biliary cancer. Therefore, patients are eligible for surveillance within well defined research programmes to establish the benefit of such surveillance.