title: The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome.
abstract: OBJECTIVE
  Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible association with the familial pancreatic cancer (FPC) risk in Poland.
  
  
  METHODS
  In this study, 400 FPC individuals and 4,000 control subjects were genotyped for founder mutations inBRCA1(5382insC, 4153delA, C61G),CHEK2(1100delC, IVS2+1G>A, del5395, I157T),NBS1(657del5), andPALB2(509_510delGA, 172_175delTTGT) genes.
  
  
  RESULTS
  A statistically significant association was observed between the 172_175delTTGT mutation of thePALB2gene and an increased risk of FPC syndrome (odds ratio [OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in the FPC family members with aBRCA1mutation (OR, 6.72; p=0.006). Novel associations were found between the FPC family members with cancer andCHEK2mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense variant, I157T ofCHEK2(OR, 2.17; p=0.026).
  
  
  CONCLUSIONS
  The founder mutations in the genes,BRCA1,PALB2, andCHEK2, cause a small percentage of familial pancreatic cancer syndrome in the Polish population. Following confirmation in larger studies, these mutations can be added to the panel of genes to be tested in families with a diagnosis of FPC syndrome.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Marcin R
authors.initials: MR
authors.lastname: Lener
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Aniruddh
authors.initials: A
authors.lastname: Kashyap
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kluźniak
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Soluch
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pietrzak
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Połabska, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology* / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D011159:Population Surveillance; D015995:Prevalence; D012306:Risk; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: CHEK2 gene; Cancer risk; Familial pancreatic cancer; Founder mutations