What do these fictitious characters have in common? Oedipus Rex, Gollum, Hamlet, Achilles. Each one had a trait called a “tragic flaw”, an innate obstacle to achieving their intended goal or desire. In myths, legends, and works of literature, it’s a vulnerability with the potential to bring about their downfall.

Many scientists hold the view that “innate traits are those that are genetically encoded. The genes of an organism are present at its conception, and so its innate traits are also present at its conception, even though only in coded form.”^[i] Sometimes, gene changes called mutations occur. Mutations can be inherited, or they can occur spontaneously in life. They can affect the genetic blueprint by disrupting gene messages, and create unexpected conditions that may remain confined to the individual or gradually spread throughout a population. Not all mutations are bad. Some, like rich color vision or resistance to hardening of the arteries, are beneficial.

However, some mutations carry a lethal potential. Such is the case with harmful mutations to two breast cancer genes, BRCA1 and BRCA2, which normally produce proteins that help repair damaged DNA. According to the National Cancer Institute, “Everyone has two copies of each of these genes—one copy inherited from each parent. BRCA 1 and BRCA2 are sometimes called tumor suppressor genes…” but mutations can cause them to fail, resulting in cancer.

The BRCA mutations are heritable, meaning they can be passed on from either parent to a child of either sex. While being born with either mutation does not doom a person to developing cancer, carrying it is like an innate tragic flaw, a vulnerability that can pose a downfall to quality of life. Even to life itself.

BRCA mutations and prostate cancer

It’s important for men to know that if they carry a BRCA mutation, they are at greater risk for prostate cancer (PCa) as well as pancreatic and breast cancer. For more information, the national organization ZeroCancer has an excellent webpage, Prostate & Breast Cancer.

How do you know if you have a harmful BRCA1 or BRCA 2 variation? Genetic testing is available, but not recommended for the general population. It is recommended, though, for at-risk people. The biggest risk factor is a family relative who had breast cancer or prostate cancer. Also, certain ethnic populations have a higher prevalence of certain BRCA variants (e.g., Ashekanzi Jewish descent, some Nordic peoples).

If you are concerned about carrying this mutation, be proactive. Talk with your doctor about a genetic test using a saliva or blood sample. Men who test positive are carriers of a potentially harmful vulnerability. The best way to overcome this “tragic flaw” is to get the jump on it. It is essential to have an annual PSA blood test, including PSA-density. If a result is abnormal, the next step is to follow up with a repeat PSA to rule out lab error or other causes of a temporary bump in PSA. If it is still abnormal, a follow-up multiparametric MRI will be able to rule suspicion of PCa in or out.

Naturally, there are some men who fear that getting this blood draw each year will make them more worried, feeling as if they’re walking around with threat hanging over them. Hopefully, a new study can put their mind at ease. It’s called the IMPACT study (‘Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls’).^[ii]

There were 760 men who enrolled in the longitudinal (5 year) study:

• 207 carried BRCA1
• 265 carried BRCA2
• 288 were non-carriers (did not inherit) from families with a known BRCA variant.

All received annual PSA screenings. Each time they also complete questionnaires to monitor their quality life over things like depression, anxiety, and cancer education that they received from initial genetic counseling. As you might expect, the non-carrier group had less PCa worry compared with the carriers, but in the words of the researchers, “We found no evidence of clinically concerning levels of general or cancer-specific distress or poor health-related quality of life in the cohort as a whole.”

Their conclusion was reassuring. Annual PSA screening for carriers of BRCA1 or BRCA2 “does not have an adverse impact on psychosocial health or health-related quality of life in these higher-risk individuals.” At the Sperling Prostate Center, we agree that PSA screening is highly important for men with the BRCA variants, and we want to emphasize the value of early detection especially given the ongoing evolution of effective PCa treatments matched to PCa patients with BRCA mutations.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Mameli M, Bateson P. An evaluation of the concept of innateness. Philos Trans R Soc Lond B Biol Sci. 2011 Feb 12;366(1563):436-43.
[ii] Bancroft EK, Page EC, Brook MN, Pope J et al. The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers. BJU Int. 2024 Jun 5.