A novel founder CHEK2 mutation is associated with increased prostate cancer risk.
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.
Cybulski
Cezary
C
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. cezarycy@sci.pam.szczecin.pl
Huzarski
Tomasz
T
Górski
Bohdan
B
Masojć
Bartłomiej
B
Mierzejewski
Marek
M
Debniak
Tadeusz
T
Gliniewicz
Bartłomiej
B
Matyjasik
Joanna
J
Złowocka
Elzbieta
E
Kurzawski
Grzegorz
G
Sikorski
Andrzej
A
Posmyk
Michał
M
Szwiec
Marek
M
Czajka
Ryszard
R
Narod
Steven A
SA
Lubiński
Jan
J
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*
D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases