title: A novel founder CHEK2 mutation is associated with increased prostate cancer risk.
abstract: Variants in the CHEK2 have been found to be associated with prostate cancer risk in the United States and Finland. We sequenced CHEK2 gene in 140 Polish patients with prostate cancer and then genotyped the three detected variants in a larger series of prostate cancer cases and controls. CHEK2 truncating mutations (IVS2 + 1G>A or 1100delC) were identified in 9 of 1921 controls (0.5%) and in 11 of 690 (1.6%) unselected patients with prostate cancer [odds ratio (OR) = 3.4; P = 0.004]. These mutations were found in 4 of 98 familial prostate cases (OR = 9.0; P = 0.0002). The missense variant I157T was also more frequent in men with prostate cancer (7.8%) than in controls (4.8%), but the relative risk was more modest (OR = 1.7; P = 0.03). I157T was identified in 16% of men with familial prostate cancer (OR = 3.8; P = 0.00002). Loss of the wild-type CHEK2 allele was not observed in any of prostate cancers from five men who carried CHEK2-truncating mutations. Our results provide evidence that the two truncating mutations of CHEK2 confer a moderate risk of prostate cancer in Polish men and that the missense change appears to confer a modest risk.
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. cezarycy@sci.pam.szczecin.pl
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Masojć
authors.forename: Marek
authors.initials: M
authors.lastname: Mierzejewski
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Gliniewicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Matyjasik
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Złowocka
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Sikorski
authors.forename: Michał
authors.initials: M
authors.lastname: Posmyk
authors.forename: Marek
authors.initials: M
authors.lastname: Szwiec
authors.forename: Ryszard
authors.initials: R
authors.lastname: Czajka
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000368:Aged; D064447:Checkpoint Kinase 2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D011471:Prostatic 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