Quest — Quest Summer/Fall 2017
Change Language:
Genetic Tests For Germline Mutations

Unlike “genomic” tests, which look at gene expression in men with newly diagnosed prostate cancer, “genetic” tests look for germline mutations known to be associated with hereditary prostate cancer. Genetic tests may be useful in identifying patients and their relatives who may have more aggressive disease and/or be susceptible to other life-threatening cancers. Commercial "genetic" tests vary in cost from a few hundred to several thousand dollars and are available to any man with prostate cancer.

Some of the mutations the tests look for are DNA repair gene mutations, BRCA1 and BRCA2, Lynch syndrome mutations, HOXB13, and ATM mutations, among others.

DNA repair gene mutations

At least 34 are associated with prostate cancer. Many of these DNA repair mutations cause DNA repair to be less effective than normal.


BRCA1 and BRCA2 are tumor suppressor genes involved in the repair of DNA damage. They occur very infrequently in the general population, but men who carry mutations in the gene have an increased risk of developing prostate cancer. Men who carry BRCA1 mutations have an approximately 3.8-fold increased risk of developing prostate cancer before age 65, and men younger than 65 who carry a BRCA2 pathogenic mutation have an up to 7.3-fold increased risk in developing prostate cancer. In addition, prostate cancers with BRCA2 mutations are more aggressive.

Lynch syndrome

Lynch syndrome mutations are germline mutations in one of the mismatch repair (MMR) genes. This leads to accumulation of mutations that can lead to cells becoming malignant. Mutation carriers have a 3.2-fold increased risk of developing prostate cancer. For the MMR gene MSH2, the risk is 5.8-fold higher. Lynch syndrome germline mutations predispose to a high lifetime risk of colorectal, upper GI, ovarian and upper urinary tract cancers. Germline gene sequencing can provide a definitive diagnosis.