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The BRCA genes: Men are not exempt

Link to prostate cancer as well

Karen Miller
The BRCA genes: Men are not exempt

There is a common misperception that mutations in the BRCA1 and BRCA2 genes are relevant to women only. Not so. Everyone — both men and women — are born with BRCA genes.

It is also assumed that mutations in these genes are linked to only female cancers, particularly of the breast and ovaries. That’s not true either.

A mutation in one of the BRCA genes may also increase the risk of prostate cancer as well as pancreatic cancer and melanoma.

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The confusion is understandable. When the BRCA genes were discovered in the late 1990s, it was their impact on breast cancer that gained attention. The genes were even dubbed the BReast CAncer genes. In actuality, they were named for Berkeley, California, where they were discovered, but the female acronym took hold and stuck.

Breast and prostate cancers have some similarities. They are the most common cancer in women and men, respectively, and the second most deadly cancer. Both are hormone driven.

Prostate cancer is very common, so it is not surprising when it strikes. As oft-repeated, “men die with, and not of, prostate cancer.” Yet, in five to 10% of the cases, the cause is due to a hereditary genetic mishap passed down from generation to generation. If one parent has the mutation, there’s a 50% chance of passing it on to each offspring.

Dr. Keyan Salari is a urologic oncologist
in the Prostate Cancer Genetic Clinic at Massachusetts General Hospital. PHOTO: Courtesy of Massachusetts General Hospital

There are specific signs suggestive of a hereditary cause, according to Dr. Keyan Salari, urologic oncologist in the Prostate Cancer Genetics Clinic at Massachusetts General Hospital. Look for multiple cases of aggressive prostate cancer or associated cancers like breast and ovarian cancer on the same side of the family — either paternal or maternal. Age is also a factor. “Diagnosis of cancer under the age of 60 is more common among patients with a hereditary cancer syndrome,” he explained.

While most men are advised to start screening for prostate cancer at age 45, the guidelines are a bit different if a genetic link is suspected. “Start at age 40 or 10 years earlier than the youngest age of an afflicted family member,” advised Salari. For instance, if a man was diagnosed at the age of 48, other men in the family should consider starting screening at age 38.

Not all mutations are patently dangerous. However, a BRCA2 gene mutation increases both the risk and aggressiveness of prostate cancer. In these men, the disease occurs at an earlier age and at a higher grade, and is more likely to recur, or return.

Actually, the job of the BRCA genes is to prevent cancer. They repair DNA mistakes, control cell growth and even remove a cell if it is not functioning properly. But if the genes are turned off or not working well, the risk of cancer increases.

Generally, when assessing a man’s risk, you look at first degree relatives — father, brother or son — with prostate cancer. When a genetic component is suspected, however, you take a wider view and include women as well. Breast and ovarian cancer, especially at a young age, are strong indicators of a potential genetic link.

Affected men are at risk for more than just prostate cancer. Although rare, men with a BRCA2 mutation have increased risk for male breast cancer and are taught to do breast self-exams and undergo a yearly clinical exam.

Although women with these mutations often have the breast removed as a preventive measure, removal of the prostate is not commonly recommended. That’s because women with BRCA gene mutations have up to an 87% risk of breast cancer, while the risk for prostate cancer is closer to the much lower 30% range. Rationale is therefore less compelling. Also, the potential side effects are more significant. Erectile dysfunction and urinary problems following prostate cancer treatment can reduce the quality of life.


Treatment may differ as well. Active surveillance is commonly recommended for men with low-risk cancers confined to the prostate. Instead of treatment, they are re-evaluated every six months. “There’s an imperfect understanding of how these cancers will progress in men with a genetic mutation,” Salari explained. His current research is to identify factors that can predict the best candidates for surveillance. This is particularly important for African American men who often have more aggressive tumors.

The good news is that the Food and Drug Administration recently approved two drugs called PARP inhibitors specifically designed for men with certain genetic mutations whose cancer has spread beyond the prostate. PARP inhibitors aid in cancer cell death or prevent the growth of tumors.

Cancers commonly associated with mutations in the BRCA 1 and 2 genes:
Female breast
Male breast
Fallopian tube
Source: National Cancer Institute

Take advantage

Regardless of its availability, not enough men are taking advantage of genetic screening. At one time it was recommended only for men whose cancer had spread beyond the prostate since it was found that 12% had a mutated BRCA or related gene. Yet, it was later learned that five to 10% of men with
localized disease are found to have the mutation as well.

Recently, however, the National Comprehensive Cancer Network included genetic testing in its screening guidelines. The tests are typically covered by health insurance. These two factors might spur its demand.

If genetic testing is not offered and you fit the criteria, ask for it. “If not for you, do it for your children,” advised Salari. “They may benefit from early screening if found to have inherited the same mutation.”

You should if you have a personal or family history of one or more of the following:
Metastatic prostate cancer (cancer that has spread)
Prostate cancer diagnosed with a Gleason score of 7 or greater
Prostate cancer in three or more people on one side (maternal or paternal) of the family
Personal history of prostate cancer with a family history of breast, prostate, colon, ovarian, pancreatic or uterine cancer
Prostate cancer in an individual of Ashkenazi Jewish descent
If your doctor does not recommend a genetic test, and your history fits the description listed above, request it.
Source: Massachusetts General Hospital

A Q&A on BRCA in Men

Source: Prostate Cancer Research Institute