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.

Figure 1

Segregation of CHEK2 1100delC mutation in four families with HPC. 1100delC variant carriers are denoted by a plus sign (+), and noncarriers by a minus sign (−). An asterisk (^*)) denotes the persons with no sample available. No sample was available from affected father (II-2) in family 351, but because the mother (II-1) did not carry the mutation, the father is a likely 1100delC mutation carrier. Current age of the unaffected members or age at diagnosis for prostate cancer patients (in years) is indicated below the symbol for each family member. In each family, the index patient is marked with an arrow. Squares denote male subjects, and circles denote female subjects; black symbols denote patients with prostate cancer.