title: Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer?
abstract: Understanding of the etiology and risk of pancreatic cancer (PaCa) is still poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among PaCa patients and assessed their possible association with the risk of disease in Poland. In the study 383 PaCa patients and 4,000 control subjects were genotyped for founder mutations in: BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2 + 1G > A, del5395, I157T), NBS1 (657del5) and PALB2 (509_510delGA, 172_175delTTGT). A statistically significant association between the 657del5 mutation and an increased risk of pancreatic cancer was observed for NBS1 gene. The Slavic NBS1 gene mutation (657delACAAA) was detected in 8 of 383 (2.09%) unselected cases compared with 22 of 4,000 (0.55%) controls (OR: 3.80, p = 0.002). The PALB2 509_510delGA and 172_175delTTGT mutations combined were seen in 2 (0.52%) unselected cases of PaCa and in 8 (0.20%) of 4,000 controls (OR: 2.61, p = 0.49). For BRCA1, the three mutations combined were detected in 4 of 383 (1.04%) PaCa patients and in 17 of 4,000 (0.42%) controls (OR: 2.46, p = 0.20). CHEK2 mutations were not associated with the risk of pancreatic cancer (OR: 1.11, p = 0.72). The founder mutation in NBS1 (657del5) was associated with an increased risk of PaCa in heterozygous carriers, indicating that this mutation appears to predispose to cancer of the pancreas. By identifying pancreatic cancer risk groups, founder mutation testing in Poland should be considered for people at risk for PaCa.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Marcin R
authors.initials: MR
authors.lastname: Lener
authors.affiliation: Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle and the Hunter Medical Research Institute, Newcastle, NSW, 2308, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kluźniak
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Baszuk
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.affiliation: Division of Heath Care Ministry of Internal Affairs and Administration, Laboratory of Endoscopy, Jagiellońska 44, Szczecin, 70-382, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wiechowska-Kozłowska
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.affiliation: Department of General and Oncological Surgery, Pomeranian Medical University, Al. Powstańców Wlkp. 72, 70-111, Poland, Szczecin.
authors.forename: Józef
authors.initials: J
authors.lastname: Kładny
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pietrzak
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Soluch
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D018703:Founder Effect; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D011159:Population Surveillance; D012306:Risk
keywords: NBS1 gene; cancer risk; founder mutations; pancreatic cancer