title: BRCA1 founder mutations do not contribute to increased risk of gastric cancer in the Polish population.
abstract: BACKGROUND
  Gastric cancer (GC) is part of the spectrum of diseases linked to BRCA1 and BRCA2 mutations that increase the risk of breast and ovarian cancer. Data suggesting an increased risk of developing GC among BRCA1 and BRCA2 mutation carriers are based almost exclusively on indirect studies. The objective was to assess in a direct study whether there is a relationship between GC and selected recurrent BRCA1 and BRCA2 mutations in the Polish population.
  
  
  METHODS
  Three hundred seventeen GC patients (193 males and 124 females; mean age 59.5 ± 12.8 y) diagnosed at the Department of Gastroenterology at the Pomeranian Medical University were included in this retrospective study. All patients were genotyped for 3 BRCA1 Polish founder mutations (5382insC, C61G and 4153delA) as well as for 9 known recurrent mutations in BRCA1 and BRCA2 genes. Genotyping was performed using allele-specific oligonucleotide polymerase chain reaction (ASA-PCR) for 4153delA and 5382insC, restriction fragment length polymorphism (PCR-RFLP) for C61G and TaqMan real-time PCR for 185delAG, 3819del5, 3875del4, 5370C > T, 886delGT, 4075delGT, 5467insT, 6174delT and 8138del5.
  
  
  RESULTS
  Among tested mutations one founder BRCA1 mutation 5382insC was detected in two of 317 (0.63 %) GC cases. A comparison of frequency of detected BRCA1 founder mutations in GC patients to previously described 4570 Polish controls (0.63 % vs. 0.48 %) failed to indicate an increased risk of GC in the mutation carriers (OR = 1.3; 95 % CI 0.3-5.6, p = 0.71). A comparison of frequency of GC male cases and male controls (1.0 % vs. 0.43 %,OR = 1.5; 95 % CI 0.3-6.4, p = 0.61) allowed to formulate the same conclusion that there is no increased risk for GC for males. None of the 9 recurrent BRCA1 and BRCA2 mutations has been detected in tested GC patients.
  
  
  CONCLUSIONS
  The current study indicates that founder BRCA1 mutations reported in Polish breast/ovarian cancer patients do not contribute to increased GC risk. The nine tested recurrent BRCA1 and BRCA2 mutations were not detected in GC patients which may suggests that they are rare in GC patients in the Polish population. Further analyses, including sequencing of entire sequences of BRCA1 and BRCA2 genes, are necessary to ultimately determine the role of these two genes in GC in Poland.
authors.affiliation: Department of Gastroenterology, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin, 71-252 Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Ławniczak
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 Gastroenterology, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin, 71-252 Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Białek
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
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115 Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jaworska-Bieniek
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, Szczecin, 70-115 Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczmarek
authors.affiliation: Department of Gastroenterology, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin, 71-252 Poland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Starzyńska