CHEK2 variants associate with hereditary prostate cancer

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 prosta...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2003-11, Vol.89 (10), p.1966-1970
Main Authors: Seppälä, E H, Ikonen, T, Mononen, N, Autio, V, Rökman, A, Matikainen, M P, Tammela, T L J, Schleutker, J
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Blood & organ donations
Cancer Research
Checkpoint Kinase 2
Confidence intervals
DNA Mutational Analysis
DNA Replication
Drug Resistance
Epidemiologic Studies
Epidemiology
Finland - epidemiology
Fungal Proteins
Gene loci
Genes, Tumor Suppressor
Genetic Predisposition to Disease
Genetics and Genomics
Humans
Kinases
Male
Medical research
Medical sciences
Middle Aged
Molecular Medicine
Mutation
Nephrology. Urinary tract diseases
Odds Ratio
Oncology
Patients
Pedigree
Prevalence
Prostate cancer
Prostatic Neoplasms - epidemiology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Protein Serine-Threonine Kinases - genetics
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6601425