Prostate Cancer and Genetic Mutations

by Jane Ashley

More men are diagnosed with prostate cancer than any other cancer (except skin cancer). One in every nine men will be diagnosed with prostate cancer in their lifetime. About 60 percent of men are over 65 when diagnosed.

One In9 Men

Facts and statistics.

Almost 175,000 men in the U.S. will be diagnosed with prostate cancer in 2019. Although prostate cancer is sometimes characterized as a slow-growing, “something-else-will-kill-you” kind of cancer, prostate cancer will be responsible for over 31,500 deaths in the U.S. this year.
Stage IV prostate cancer is diagnosed when your cancer has spread to distant parts of your body. The places that prostate cancer most often spreads is to the adrenal gland, bladder, bones, brain, liver, lungs, rectum and/or lymph nodes. About 5 percent are prostate cancer cases are Stage IV when your cancer is first diagnosed. The remainder of Stage IV, late-stage diagnoses occur when your cancer spreads after treatment. 

Risk factors that may make you at increased for spread are: 

1) a family history of prostate cancer, which may indicate inherited genetic mutations, or 

2) African-Americans have an increased risk of aggressive prostate cancer.

Symptoms that your prostate cancer may have spread include:

Blood in your semen
Bone pain
A decrease in your urine stream
Fatigue
Painful urination
Swelling in the legs
Weight loss

Be sure to talk to your urologist if you have a history of prostate cancer and experience any of these symptoms.

New treatments and hope for advanced prostate cancer.

Once your prostate cancer has progressed, your medical team will determine whether your cancer is castration sensitive – that doesn’t mean that you will be castrated – it means whether your cancer will respond to treatments that lower the level of testosterone in your body. 

Castration-sensitive cancer responds well to medications, called androgen deprivation therapy that suppress testosterone production. Eventually, your cancer will become resistant to that treatment.

African American Prostate Cancer

When prostate cancer becomes “castration-resistant” – i.e., it no longer responds to androgen deprivation therapy, new evidence indicates that a patient should have genetic testing. In the past, genetic testing was only recommended for patients of Ashkenazi Jewish descent or who had a family history of breast or ovarian cancer.

New research shows that every patient with castration-resistant prostate cancer (CRPC) can benefit. New targeted therapies are providing hope for prostate cancer patients who carry the BRCA1 and BRCA2 mutations. BRCA mutations are most commonly associated with breast and ovarian cancer. Increasing evidence indicates that BRCA mutations may also play a role in aggressive prostate cancer.

You may be surprised to learn that men carry BRCA mutations. The acronym “BRCA” actually stands for BReast CAncer. Scientists have learned that both women and men may carry the BRCA1 and BRCA2 genes. BRCA genes normal function is to repair cell damage. Sometimes, these genes become mutated and no longer function correctly.

So these genes are no longer able to repair DNA damage. The result is an increased risk of breast, ovarian, prostate, pancreatic, fallopian tube, peritoneal and colorectal cancer. People of Ashkenazi Jewish ancestry along with Norwegian, Dutch, and Icelandic backgrounds tend to experience this mutation more often. In the United States, people of African-American, Asian-American and non-Hispanic whites carry BRCA mutations more frequently.

So What Next?

About 5 to 10 percent of prostate cancer is attributed to hereditary factors which include the BRCA mutation. Men with a family history of prostate cancer as well as breast and ovarian cancer face an increased risk of prostate cancer.

A New England Journal of Medicine study revealed that 11.8 percent of men with metastatic prostate cancer have BRCA mutations compared to just 2.7 percent of men with no known cancer diagnosis.

BRCA mutations are most likely seen in more aggressive prostate cancer. These patients also have a higher Gleason score, higher PSA and higher tumor stage at diagnosis.

The National Comprehensive Cancer Network (NCCN) now recommends that men whose cancer has spread beyond their prostate gland into nearby tissue and men with metastatic prostate cancer, regardless of their age, be tested by a genetic specialist. Men who know that they carry BRCA mutations or a family history should begin having PSA tests at age 45. The NCCN also recommends that men with the BRCA mutation begin having clinical breast exams at age 35.

Over 65

Treatment implications.

Researchers are conducting clinical trials to find the most effective treatment for men with BRCA mutations. The trials are testing platinum-based chemotherapy and PARP (poly-ADP ribose polymerase) inhibitors.

The PARP inhibitor being tested is olaparib, currently approved for the treatment of some ovarian cancers and metastatic breast cancer in women with the BRCA mutation. Olaparib has Breakthrough Therapy designation by FDA for metastatic hormone-resistant prostate cancer.
Other trials involving other PARP inhibitors are ongoing. Precision medicine is coming to prostate cancer.

If you have a family history of prostate cancer among your close male relatives and a family history of breast and ovarian cancer in your female relatives, talk to your family physician about genetic testing. Maybe you don’t want/care to know if you have BRCA mutations – but do it anyway – for your children’s and grandchildren’s sake.

Get your prostate checked, if caught early, one of the deadliest forms of men's cancer can be cured. Prostate cancer is a serious problem, but the video below is seriously funny about getting a prostate exam.  

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