title: CHEK2 variants associate with hereditary prostate cancer.
abstract: Recently, variants in CHEK2 gene were shown to associate with sporadic prostate cancer in the USA. In the present study from Finland, we found that the frequency of 1100delC, a truncating variant that abrogates the kinase activity, was significantly elevated among 120 patients with hereditary prostate cancer (HPC) (four out of 120 (3.3%); odds ratio 8.24; 95% confidence interval 1.49-45.54; P=0.02) compared to 480 population controls. Suggestive evidence of segregation between the 1100delC mutation and prostate cancer was seen in all positive families. In addition, I157T variant had significantly higher frequency among HPC patients (13 out of 120 (10.8%); odds ratio 2.12; 95% confidence interval 1.06-4.27; P=0.04) than the frequency 5.4% seen in the population controls. The results suggest that CHEK2 variants are low-penetrance prostate cancer predisposition alleles that contribute significantly to familial clustering of prostate cancer at the population level.
authors: Laboratory of Cancer Genetics, Institute of Medical Technology, Lenkkeilijänkatu 8,University of Tampere and Tampere University Hospital, FIN-33014 University of Tampere, Finland.
authors: E H
authors: EH
authors: Seppälä
authors: T
authors: T
authors: Ikonen
authors: N
authors: N
authors: Mononen
authors: V
authors: V
authors: Autio
authors: A
authors: A
authors: Rökman
authors: M P
authors: MP
authors: Matikainen
authors: T L J
authors: TL
authors: Tammela
authors: J
authors: J
authors: Schleutker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064447:Checkpoint Kinase 2; D004252:DNA Mutational Analysis; D004261:DNA Replication; D016021:Epidemiologic Studies; D005387:Finland / Q000453:epidemiology; D005656:Fungal Proteins; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010375:Pedigree; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases