Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer.
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.
Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer.
Furthermore, the CHEK21100delC variant carried by 1% of the population has been shown to act as a low penetrance allele for both breast and prostate cancers.
Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer.
The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 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.
The relatives of bilateral cases who were wild-type for CHEK2 had three times the population risk of female breast cancer (145 cases: SIR 3.48 (95% CI 2.96-4.09), twice the risk of prostate cancer (34 cases: SIR 2.41, 1.67-3.36) and a large excess of male breast cancer (five cases: SIR 15.06, 4.92-35.36).
Our data suggest that the CHEK2 and TP53 mutations can substitute each other in at least 25% (21/84) of prostate cancers and that DNA damage-signaling pathway plays an important role in prostate cancer tumorigenesis.
Taken together, these results provide evidence that both germline and somatic CHEK2 mutations identified in prostate cancer may contribute to the development of prostate cancer through the reduction of CHEK2 activation in response to DNA damage and/or oncogenic stress.
Germ line mutations in several genes (BRCA1, BRCA2, and CHEK2) whose products are involved in the DNA damage-signaling pathway have been implicated in prostate cancer risk.
To investigate whether it plays an important role in the development of prostate cancer (PRCA) in the Ashkenazi Jewish (AJ) population, we sequenced CHEK2 in 75 AJ individuals with prostate, breast, or no cancer (n=25 each).
Intriguingly, two other CHEK2 mutations (IVS2+1G>A and I157T) and a CHEK2 large genomic deletion (del9-10) have been associated with an elevated risk for prostate cancer.
Germline mutations in CHEK2 have been associated with a range of cancer types but little is known about disease risks conveyed by CHEK2 mutations outside of the context of breast and prostate cancer.
Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied.
These results suggest that testing for germline CHEK2 mutations improves the ability to predict the presence of prostate cancer in screened men, however, the clinical utility of incorporating DNA variants in the screening process is marginal.