The purpose of this article is to provide a review of principles of genetic testing in prostate cancer and highlight the significance of clinical genetic testing of BRCA1/2 and other genes (CHEK2, HOXB13, PALB2), including Lynch syndrome genes (MLH1, MSH2, MSH6, and PMS2) in men with metastatic prostate cancer.
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).
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.
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.
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.
To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients.
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).
We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4.