PALB2:
PALP2 mutation is associated with 6.3 higher risk for aggressive PCa74. The rate of PALB2 somatic mutation is not significantly higher between EAM (0.83%) and AAM (2.16%) with metastatic PCa (Table 1)67. The rates of PALB2 germline mutation, on the other hand, is similar in both races with a range from 0.43 to 0.5% in EAM and from 0 to 0.5 % in AAM with metastatic prostate cancer (Table 2)6465.
CHEK2 :
CHEK2 is a tumor suppressor gene located on chromosome 22q and is associated with a significantly higher prevalence in men with metastatic PCa compared with localized PCa. CHEK2 encodes a cell cycle checkpoint protein kinase that plays a role in the regulation of tumor protein 53 (TP53) and DNA repair. The rates of CHEK2 somatic mutations is 2.32% in EAM and 1.08% in AAM (Table 1)67. The studies reported CHEK2 germline mutation range from 1.01-2% in EAM and 0% germline mutation rate in the AAM (Table 2)6465.
Lynch syndrome:
Lynch syndrome is an inherited cancer predisposition syndrome with an increased risk of numerous malignancies, doubling the risk of PCa. It is caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 and PMS275. The included studies show a rate of somatic mutations in the EAM population ranging from 1.30-1.76%. The AAM population presents a similar expression rate with a range that varies from 1.08-1.62% (Table 1)67. Regarding germline mutations, the EAM population presented a range from 0.14-0.70%, while the AAM population presented a range from 0.0-1.80% (Table 2)64 65 71.
NBN :
NBN encodes for Nibrin a protein within the Mre11-RAD50-NBS1 double-stranded DNA break repair complex. NBN is a newly emerged gene that is identified as PCa-susceptibile76. For the NBN mutation, the included studies presented a somatic mutation rate of 0.65% in EAM, while the AAM population presented a rate of 1.08% (Table 1)67. The EAM population presented a germline mutation rate of 0.0-1% while the AAM population has an NBN germline mutation rate of 0.0-0.9%(Table 2)6465 71.