Prostate Cancer and Your Genes

If your mom had breast cancer, that could raise your risk for prostate cancer.  If you have aggressive prostate cancer, your daughter might be at higher risk for ovarian or breast cancer.  Some “bad apple” genes run in families; doctors know what they are, and there’s a blood test to look for them.

For the last two decades or so, doctors and scientists have talked a lot about genes and genetic testing, and about gene-fixing medicines that can stop cancer in its tracks. Until recently, with a few exceptions, that’s mostly what it has been: talk, and frankly, a fair amount of hype.

That’s changing.  I recently interviewed Jonathan Simons, M.D., medical oncologist and molecular biologist, and also President and CEO of the Prostate Cancer Foundation, which has funded some of the most exciting research in this area.   “Everybody talks about genes,” he says.  “But what really matters is, how does it help you?  How can it help your children and grandchildren?” 

A new blood test called the Cascade Genetic Test looks for mutations in several known “bad apple” genes.  These are genes that are supposed to repair DNA damage. When they malfunction, it is easier for cancer to develop. 

What does this mean to you?  Well, say you’re a man with a rising PSA, and a biopsy shows just a small amount of low-grade cancer.  Your doctor might want to wait and do another biopsy in six months to a year, and you might decide to get yet another biopsy a few months after that.  But what if you could add a very important piece of extra knowledge to the puzzle?  What if you could find out whether you have one of these bad genes?  That might lead you to seek treatment right away, before the cancer has a chance to get established outside the prostate. 

Another thing: “If a man tests positive for one of these genes, his sisters, brothers, and children will need genetic testing, as well, because of the high probability that their cancer risk has been significantly elevated,” says Simons.  “Men on active surveillance should have these genes tested.”

Very important: Testing positive is not a cause for alarm, or for making panicky, hasty decisions.  “Genes don’t have to be your destiny,” notes Simons. 

In other words, if you have one or more of these genetic mutations, cancer is not a done deal.  But it’s on the table.

A man diagnosed with prostate cancer who has one of these mutated genes needs to take that cancer diagnosis very seriously, even if it seems to be low-level, “safe” prostate cancer. 

It turns out that more than half of American men are carrying a gene that they inherited from either their mother or their father that increases their chances of getting prostate cancer.  “We now know that prostate cancer is perhaps the most heritable of all the major cancers,” says Simons.  Again, having one of these bad genes doesn’t mean that cancer is inevitable – which also means that having a healthy diet and lifestyle may help prevent cancer from ever getting started – but it can make it easier for cancer to spread and become difficult to treat.

“The genes tell their story,” says Simons.  The good news is that, for the first time, a test can provide the Cliff’s Notes preview of what that story might be.   For more on this test, keep reading.

Bad “Spell-checker” Genes

An important study, led by Fred Hutchinson Cancer Research Center medical oncologist Peter Nelson, M.D., funded in part by the Prostate Cancer Foundation, and published in the New England Journal of Medicine, is changing how we think about prostate cancer. What Nelson has found can be summed up like this: 

Prostate cancer is a lot more of an inherited disease than anybody thought;

There are 16 bad genes that we now know to look for; and

If you have a mutation in one of these genes, your sons and daughters, and their children need to know about it, because they are more likely to develop cancer, too.

Every gene has a job.  Some of them act like brakes that control cell growth; some do just the opposite, and instead of curbing growth, they step on the accelerator and speed it up in a bad way.  Some genes are tiny Xerox machines, making genetic copies.  And some genes are little quality control specialists; they’re the spell checkers. 

The genetic mutations we are born with are called germline mutations.  Those are different from the kind of incremental gene mutations that develop over time – through exposure to carcinogens in cigarettes, for example, or eating a bad diet, or drinking too much alcohol.   

Nelson’s study looked at these inherited mutations in 20 spell-checker, or “DNA-repair,” genes, in 692 men with metastatic prostate cancer at institutions in the U.S. and United Kingdom.  They found mutations in 16 of them, including some unexpected ones, like BRCA1 and BRCA2. 

“Now wait,” you may be thinking, “aren’t they the breast cancer genes?”  Yes, and for years, these genes were not significantly linked to prostate cancer.  Now we know that the very same mutation that can cause breast and ovarian cancer in women can cause lethal prostate cancer in men. 

Other bad DNA-repair genes include one that sounds like it should be at a bank, called ATM; and one that sounds like a roadie making sure the microphones work at a concert, called CHEK2; there’s RAD51D; and one that sounds friendly but isn’t at all, called PALB2, which is strongly involved in pancreatic and breast cancer.

These gene mutations are rare in the general population, but startlingly common in men with metastatic prostate cancer:  Because of this work, Nelson and colleagues estimate that one in nine – 12 percent – of men with metastatic cancer have them, even if they have no family history of prostate, breast, or ovarian cancer. 

And this last part is actually hopeful because it means that cancer is not inevitable if you carry one of these mutations.  It may well be that if you live your life doing some things that we know help prevent or delay prostate cancer – not eating a lot of red meat and dairy products, eating foods like broccoli and tomatoes, not smoking, not drinking an excessive amount of alcohol, and not being overweight, which adds stress to your cells and makes them less resistant to cancer – that you will never develop prostate cancer.  And if you start getting screened for prostate cancer at age 40, and if you are then screened every year to look for changes in your PSA and other markers, that if you do develop cancer, it will be caught early and you will be cured.

So don’t despair.  But if you have metastatic prostate cancer, Nelson recommends that you get genetic testing, because your kids and grandkids need to know if one of these bad genes runs in the family – so they can be considered high-risk for certain types of cancer, screened vigilantly, treated aggressively if cancer is found, and most important of all, live to a ripe old age and not die of cancer.

Other hopeful news:  There are entirely new kinds of cancer-fighting drugs that target specific genes.  One class of drugs is known as PARP inhibitors, and the standout in this class is Olaparib, which is being used to treat women with BRCA mutations in ovarian cancer.  It has now been approved as a treatment for advanced prostate cancer in some men. 

What should you do?  If you have high-risk or metastatic prostate cancer, or if you have a strong family history of prostate or other cancers, ask your doctor about this test. It costs $250 at Color Genomics.

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, 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.

 ©Janet Farrar Worthington