Research study the role of BRCA1 mutations in initiating prostate cancer

Mutations in the BRCA1 gene, which are inherited (embryo line) or acquired (somatic), may not be the key to initiating prostate cancer, as previously thought, suggests the first such study, published online in the journal Open Access Journal

In the case of further studies confirmed, the results suggest that there may be time to re-treatment PARP (polymerase of poly (ADP-Rybose)), which block cell ability, including cancer cells, to repair DNA damage, in men say researchers with variants genetic BRCA1.

The combined editorial article suggests that discoveries pave the way for a greater improvement of genetic tests and personalized treatment of men with prostate cancer.

Prostate cancer is the most common cancer in men, and it is known that genetic variants in repairing DNA damage and response genes play a role in the progress of the disease.

For example, men with inherited or acquired mutations in the BRCA2 or ATM genes are exposed to the risk of aggressive illness and have worse results than those who do not have these mutations, explain researchers.

To try to estimate the participation of inherited and acquired mutations in various genes of DNA repair and response in men with prostate cancer, scientists reviewed the results of a genetic test 450 men with disease in north -western England in 2022–2024.

Men were tested in terms of the embryonic line (166), somatic (280), or both types (4) genetic variants of the BRCA1, BRCA2, ATM, CDK12 and PALB2 genes, with a view to starting them in the treatment of PARP inhibitor.

In 340 cases, men’s cancer spread elsewhere (metastasis). Their average age was 69, but ranged from 38 to 87.

Among the people in this group who were not tested, based on the history of high risk or family history-at least 18 (just over 5%), they had a BRCA2 germ variant, but only 1 had a BRCA1 variant (0.3%). And out of 263 respondents in terms of ATM variants of the 7 (3%) ATM line (3%) tested a positive result.

Of the 124 germ lines tested, based on high risk, their average age was 56 (range 34–77). Again, the BRCA2 germ variety dominated, and 8 (8%) tested positive, but only one (less than 1%) positive for the BRCA1 variant of the embryonic line.

The results of the BRCA 1 and BRCA 2 test were available to all 450 men. They revealed 27 BRCA2 variants of the embryonic line (6%), but only 2 variants of the BRCA1 embryonic line (0.5%), and one of them was probably not a driver, because the ATM mutation was also present, notice scientists.

Six variants of the ATM embryo line were found among 328 men tested for this genetic mutation. And out of 97 men tested for Palb2 variants, only 1 found in a man in the 70s with a strong family history of breast cancer.

Of those that were tested on CHEK2 (122), for Lynch (69) or for RAD51C/D (15) Genetic mutationsNo one was found.

The results of the somatic test were available to 280 men whose cancer spread elsewhere. Generally 31 (11%) the BRCA2 genetic variant could be identified. Of these, 16 (6%) the embryo line was confirmed, and 11 (4%) confirmed somatic. The type of variant was unclear in 4.

This indicates that BRCA2 variants, somatic and embryonic, play the main role in progression progression of prostate cancer, which affects at least 1 in 10 carriers with the disease, the scientists say.

On the other hand, the BRCA1 variants do not seem to be the main factor contributing to the initiation of diseases or progression, with only 1 somatic variant and 1 variant of the embryonic line found in combination with the ATM variant of the embryonic line in one case in which the disease spread elsewhere.

Both the mutations of the germ and somatic ATM were also associated with the spread of the disease, because 16 out of 263 (6%) tested tumor samples had identified ATM genetic variants, of which 5 (2%) was a germ line, 7 (2.5 %), of which 2.5%) somatic and 4 were indefinite.

And the data suggest that the somatic CDK12 and Somatic and the BRCA2 embryo should no longer be considered mutually exclusive, as before.

Scientists admit that only 217 tumor samples were tested for all genetic variants and that they were not able to classify all identified as somatic or embryonic. And because the carriers of BRCA1 variants have recently been tested, long -term results for these men are not yet known.

“Even if there is a signal for unobtitutative prostate cancer in BRCA1, this may not justify the dog [prostate specific antigen] Screening, taking into account the high indicators of excessive diagnosis, “scientists say.

“Therefore, it may be time to ask whether BRCA1 should be considered a gene predisposing prostate cancer, taking into account its very low spread in this study of somatic mutations,” suggest.

In the related editorial office of DRS Fumihiko Uraba and Kosuke Takiemura, respectively, Jikei University School of Medicine, Minato, Japan Research results.

“[They] Strengthen the role of BRCA2 and ATM as key determinants of aggressive phenotypes of prostate cancer. BRCA1 limited involvement suggests that tumors containing BRCA1 variants may not rely on a homologous repair shortage, potentially limiting their reaction to PARP [inhibitor]-Parned on therapies -you will help the authors.

They add: “Mutations CDK12, previously considered to be mutually exclusive from BRCA2, were observed in combination with BRCA2 mutations, which suggests the potential of double target therapy connecting PARP [inhibitors] AND immunotherapy. “

They suggest that giving the same aggressive potential of both BRCA1 and BRCA2 is probably appropriate.

“Although many earlier clinical trials were divided into BRCA1 and BRCA2 mutations as a single group (BRCA1/2), these studies lead to the conclusion that BRCA1 and BRCA2 should be analyzed separately,” they say.

“If the Post Hoc analysis of previous clinical trials that grouped BRCA1/2 mutations reveal various therapeutic effects, this may require re -assessment of the interpretation of BRCA1 and BRCA2 mutations in prostate cancer,” they add.

Although further research is justified in more diverse groups of patients, the results of the study “pave the way to improve the strategy of genetic testing and personalized approaches to the treatment of prostate cancer”, they conclude.