British Journal of Cancer · 2003 · 145 citations · 21 references
MedicineGeneticsMolecular GeneticsCancer GeneticsMedical GeneticsMolecular OncologyCancer ClusteringCancer GenomicsFamilial Cancer AggregationHereditary Cancer SyndromesHereditary Urologic Cancer SyndromesProstate CancerCancer Risk AssociationChek2-related Cancer PredispositionFamilial Clustering AnalysisGenetic Predisposition To CancerGenetic Susceptibility To Prostate CancerHereditary Prostate CancerProtein-truncating Variant EffectsProtein-truncating Variants
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.
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