Does Cancer Run in Your Family?

If you have high-risk or metastatic prostate cancer, you may have been born with a faulty gene, and you should strongly consider “germline” genetic testing, testing of the genes you were born with. 

In my work for the Prostate Cancer Foundation, I recently interviewed an expert on germline genetic testing (despite the name, it has nothing to do with germs, as one patient asked me!):  Alexandra Sokolova, M.D., medical oncologist at Oregon Health Sciences University.  She told me a sobering story:  One of her patients, Eddie,* was diagnosed with metastatic prostate cancer.  Sokolova did germline genetic testing (looking at Eddie’s blood for inherited, cancer-linked mutations) and discovered a faulty BRCA2 gene – a mutation most famous for raising the risk of breast and ovarian cancers (see below).  Eddie said, “My sister has that.”

            One sister had been diagnosed with breast cancer years before. “All his sisters got germline genetic testing,” says Sokolova (this is called “cascade genetic testing,” of family members after someone is diagnosed with a mutated gene). “But he didn’t – because he was a man.”

Eddie and his family didn’t think this gene was something he needed to worry about, and for many years, doctors didn’t think so, either.  Even BRCA2’s name (an abbreviation for “BReast CAncer gene”) and the syndrome it is associated with (Hereditary Breast and Ovarian Cancer Syndrome) now seem misleading – because mutations in BRCA2and BRCA1, a related gene, are known to raise the risk of prostate cancer, too (see side story).  These and others are “DNA damage-repair genes” – genes that are supposed to act as quality control agents, preventing genetic mistakes from being passed on when a cell divides.

            If Eddie had known he was at higher risk, his prostate cancer might have been detected much earlier.  Sokolova thinks about Eddie a lot, and she has dedicated her career to helping high-risk patients and their families.  “About 12 percent of men diagnosed with metastatic prostate cancer were born with a bad gene,” she says.  “If you inherited a mutation in BRCA1 or BRCA2, you are not only at higher risk of getting certain cancers, including prostate cancer:  you are also likely to develop a more aggressive form of prostate cancer.  Patients with these mutations tend to be diagnosed at a younger age, at a more advanced stage of prostate cancer, and are more likely to have a shorter survival.”

            Early knowledge is a game-changer.  The best help Sokolova can provide for patients like Eddie is to arm him and his family with information that could save their lives:  to test men diagnosed with high-risk or metastatic prostate cancer and, if BRCA2 or a similar faulty gene is found, to do “cascade” testing – to test his immediate family.

An inherited cancer gene has a ripple effect.  “If your mother had an inherited BRCA2 mutation, there is a one-in-two (50 percent) chance that you or your siblings inherited the same mutation, and a 25 percent chance that your children did.  Just knowing you have such a gene mutation has significant implications for treatment decisions.”  For example, if you know the genetic deck is stacked and not in your favor, you should consider more aggressive, curative treatment for prostate cancer.  Also, germline testing can identify patients who are candidates for PARP inhibitors, drugs such as olaparib that have proven effective in cancers when there is a mutated DNA repair gene.  Another advantage of early knowledge, Sokolova continues:  “At-risk family members can implement cancer prevention and early detection strategies, and possibly consider risk-reduction surgery.”

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**Key Terms**

Germline genetic mutations:  changes in genes (DNA) you are born with, passed on from either your mother or father. These are different from somatic mutations (found in tumor cells), which are acquired over time, and in which environmental factors play a role.

Cascade genetic testing:  testing family members after someone is found to have a germline (inherited) mutation.

BRCA2: a DNA repair gene.  Its job is to correct errors in DNA, and when it is not working, those mistakes don’t get fixed – and cancer can result.  Inherited mutations in BRCA2 and a related gene, BRCA1, are associated with a higher risk of breast, ovarian, pancreatic, and prostate cancer, among other cancers.  Other mutated DNA repair genes are linked to prostate cancer, too, including ATM, PALB2, and CHEK2.

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Up next, Part 2:  Who should consider germline testing?

In addition to the book, I have written about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org.  I firmly believe that knowledge is power.  Saving your life may start with you going to the doctor and knowing the right questions to ask.  I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease.  Many doctors don’t do this, so it’s up to you to ask for it.  Note: I am now adding, because people are being diagnosed with many kinds of cancer at younger ages than ever:  If you have cancer in your family, ask your doctor for a baseline PSA test in your 30s.  If you are getting blood work anyway, it’s just one more box for the doctor to check.  Then, to see if your number is right for your age group, refer here.  

©Janet Farrar Worthington