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Page 131 Connors. J Transl Genet Genom 2021;5:130-2 https://dx.doi.org/10.20517/jtgg.2021.17

BRCA AND MALE SPECIFIC CANCER
Prostate cancer is one of the most common cancers in men and those impacted with aggressive or
metastatic disease should complete genetic testing with next generation sequencing of the BRCA genes. For
the past years, the National Comprehensive Cancer Network (NCCN) guidelines for hereditary breast and
[5]
ovarian cancesr have included the consideration of BRCA1 and BRCA2 genetic testing for men who meet
certain criteria, including a prostate cancer diagnosis with Gleason score of ≥ 7 or metastatic prostate cancer
[6]
(NCCN, Genetic/Familial High-Risk Assessment Breast and Ovarian 2019a). Pritchard et al. identified the
importance of germline genetic testing in men with metastatic prostate cancer, BRCA2 representing the
most identified pathogenic variant.

There is clinical utility in establishing the presence of mutations in DNA repair genes, such as BRCA, to
define cancer subtypes that have distinct vulnerabilities to specific therapeutic such as Poly [adenosine
[7]
diphosphate (ADP)-ribose] polymerase (PARP) inhibitors . Poly (ADP-ribose) polymerase is a cellular
mechanism for repairing single-strand DNA breaks. If BRCA is mutated, PARP must repair both types of
DNA breaks, and cells depend on the PARP repair mechanism. Therefore, use of the PARP inhibitors class
of medications in individuals with BRCA1 and BRCA2 mutations should result in cancer cell death through
a type of directed synthetic lethality . Poly (ADP-ribose) polymerase inhibitors are a consideration for the
[8]
treatment of ovarian and breast cancers with germline BRCA1 and BRCA2 mutations and have activity in
castration-resistant prostate cancer with germline or somatic mutations in certain DNA repair genes, such
as BRCA1, and BRCA2 .
[7]
HAVE BEEN HERE BEFORE
There has been a similar circumstance in cancer genetics with the re-naming of hereditary non-polyposis
colorectal cancer to Lynch syndrome . Lynch syndrome is a hereditary cancer syndrome associated with an
[9]
increased lifetime risk of developing colorectal cancer as well as stomach cancer, ovarian cancer,
hepatobiliary tract cancer, urinary tract cancer, and cancers of small bowel, brain, and skin. Lynch
syndrome is associated with pathogenic genetic variants in multiple different genes, including MLH1,
MSH2, MSH6, and PMS2, which are considered to mismatch repair genes and have therapeutic implications
[10]
specific to immunotherapy . Previous research demonstrated the benefit of testing tumors and patients for
Lynch syndrome as the questionable benefit of standard systemic chemotherapy regimens based on cisplatin
and 5-fluorouracil in the setting of mutations in mismatch repair genes [11-14] . Lynch Syndrome provides an
early adoption of molecular analysis of solid tumor patients to guide individual oncology treatment and by
removing the colorectal cancer focus to the syndrome, a wider net became available to capture cancers
associated with mutations in the mismatch repair genes.

It is timely and necessary to rename hereditary breast and ovarian cancer syndrome to King syndrome, to
assume a wider assessment of cancer that has occurred, or may occur, and due pathogenic variants in
BRCA1 or BRCA2. Genetic testing and molecular analysis for oncology patients of all genders (female, male,
and trans) and cancer types (breast, ovarian, pancreas, and prostate) is necessary if the true benefit of
personalized medicine is to be gained for the entire population. King syndrome would raise awareness and
expand health care provider consideration of genetic testing for cancers other than only breast and ovarian.
By a simple name change, King syndrome provides a broader scope to impact health outcomes and save
lives.

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.