title: Pancreatic cancer-associated gene polymorphisms in a nation-wide cohort of p16-Leiden germline mutation carriers; a case-control study.
abstract: BACKGROUND
  The p16-Leiden founder mutation in the CDKN2A gene is the most common cause of Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome in the Netherlands. Individuals with this mutation are at increased risk for developing melanoma of the skin, as well as pancreatic cancer. However, there is a notable interfamilial variability in the occurrence of pancreatic cancer among p16-Leiden families. We aimed to test whether previously identified genetic risk factors for pancreatic cancer modify the risk for pancreatic cancer in p16-Leiden germline mutation carriers.
  
  
  METHODS
  Seven pancreatic cancer-associated SNPs were selected from the literature and were genotyped in a cohort of 185 p16-Leiden germline mutation carriers from 88 families, including 50 cases (median age 55 years) with pancreatic cancer and 135 controls (median age 64 years) without pancreatic cancer. Allelic odds ratios per SNP were calculated.
  
  
  RESULTS
  No significant association with pancreatic cancer was found for any of the seven SNPs.
  
  
  CONCLUSIONS
  Since genetic modifiers for developing melanoma have already been identified in CDKN2A mutation carriers, this study does not exclude that genetic modifiers do not play a role in the individual pancreatic cancer risk in this cohort of p16-Leiden germline mutation carriers. The search for these modifiers should therefore continue, because they can potentially facilitate more targeted pancreatic surveillance programs.
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. t.p.potjer@lumc.nl.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Potjer
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. n.van_der_stoep@lumc.nl.
authors.forename: Nienke
authors.initials: N
authors.lastname: van der Stoep
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands. J.J.Houwing@lumc.nl.
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.affiliation: Department of Gastroenterology and Hepatology,Erasmus MC, University Medical Center, Rotterdam, The Netherlands. i.konings@erasmusmc.nl.
authors.forename: Ingrid C A W
authors.initials: IC
authors.lastname: Konings
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. c.m.aalfs@amc.uva.nl.
authors.forename: Cora M
authors.initials: CM
authors.lastname: Aalfs
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. p.c.van.den.akker@umcg.nl.
authors.forename: Peter C
authors.initials: PC
authors.lastname: van den Akker
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. M.G.E.M.Ausems@umcutrecht.nl.
authors.forename: Margreet G
authors.initials: MG
authors.lastname: Ausems
authors.affiliation: Department of Clinical Genetics and Human Genetics, VU University Medical Center, Amsterdam, The Netherlands. CJ.Dommering@vumc.nl.
authors.forename: Charlotte J
authors.initials: CJ
authors.lastname: Dommering
authors.affiliation: Department of Clinical Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. l.vd.kolk@nki.nl.
authors.forename: Lizet E
authors.initials: LE
authors.lastname: van der Kolk
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands. merel.maiburg@mumc.nl.
authors.forename: Merel C
authors.initials: MC
authors.lastname: Maiburg
authors.affiliation: Department of Clinical Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands. Liesbeth.Spruijt@radboudumc.nl.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Spruijt
authors.affiliation: Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. a.wagner@erasmusmc.nl.
authors.forename: Anja
authors.initials: A
authors.lastname: Wagner
authors.affiliation: The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands. hfavasen@stoet.nl.
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. f.j.hes@lumc.nl.
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Hes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004416:Dysplastic Nevus Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012878:Skin Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16