title: CHEK2 variants predispose to benign, borderline and low-grade invasive ovarian tumors.
abstract: OBJECTIVE
  Three founder alleles of the CHEK2 gene have been associated with predisposition to a range of cancer types in Poland. Two founder alleles (1100delC and IVS2 + 1G >A) result in a truncated CHEK2 protein and the other is a missense substitution, leading to the replacement of a threonine with an isoleucine (I157T).
  
  
  METHODS
  To establish if these variants play a role in the etiology of ovarian tumors, we genotyped 1108 Polish women with various types of ovarian tumors and 4000 controls for the three CHEK2 variants. We included 539 Polish women with benign ovarian cystadenomas, 122 women with borderline ovarian malignancies and 447 women with invasive ovarian cancer.
  
  
  RESULTS
  Positive associations were seen with the CHEK2 I157T missense variant and ovarian cystadenomas (OR = 1.7; P = 0.005), with borderline ovarian cancers (OR = 2.6; P = 0.002) and with low-grade invasive cancers (OR = 2.1; P = 0.04). There was no association with ovarian cancer of high grade (OR = 1.0). The association between the I157T missense variant was then confirmed in a second sample of Russian patients with borderline ovarian cancers (OR = 2.7; P = 0.06).
  
  
  CONCLUSIONS
  These data indicate that CHEK2 variants may predispose to a range of ovarian tumor types of low malignant potential, but not to aggressive cancers.
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Szymanska-Pasternak
authors.forename: A
authors.initials: A
authors.lastname: Szymanska
authors.forename: K
authors.initials: K
authors.lastname: Medrek
authors.forename: E N
authors.initials: EN
authors.lastname: Imyanitov
authors.forename: C
authors.initials: C
authors.lastname: Cybulski
authors.forename: B
authors.initials: B
authors.lastname: Gorski
authors.forename: P
authors.initials: P
authors.lastname: Magnowski
authors.forename: I
authors.initials: I
authors.lastname: Dziuba
authors.forename: K
authors.initials: K
authors.lastname: Gugala
authors.forename: B
authors.initials: B
authors.lastname: Debniak
authors.forename: S
authors.initials: S
authors.lastname: Gozdz
authors.forename: A P
authors.initials: AP
authors.lastname: Sokolenko
authors.forename: N Y
authors.initials: NY
authors.lastname: Krylova
authors.forename: O S
authors.initials: OS
authors.lastname: Lobeiko
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: J
authors.initials: J
authors.lastname: Lubinski
mesh_terms: D064447:Checkpoint Kinase 2; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases