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Why Genes Matter

Revolution.  It’s a shame that we tend to use that word so freely—to describe, say, a new style of men’s briefs, or a hand-crafted microbrew, or an engine-protecting motor oil.  Because if ever we needed a word that packs a punch, it’s now.

This revolution has to do with your genes, and maybe you’re not terribly excited because you’ve heard all that before.  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.

Now all that science—the millions of dollars being poured into genetic research programs, the decades of study, trial and error, and moments of insight and discovery—has finally reached critical momentum, and new breakthroughs, many of them funded by the Prostate Cancer Foundation, are happening almost daily.

“Everybody talks about genes,” says medical oncologist and molecular biologist Jonathan Simons, M.D., President and CEO of the Prostate Cancer Foundation. “But what really matters is, how does it help you?  How can it help your children and grandchildren?”

What’s about to change in prostate cancer—and, because of PCF-funded research, these discoveries will also help people at risk for breast cancer, pancreatic cancer, colon cancer, melanoma, lung cancer, and other cancers – is the conventional way of treating the disease. The traditional approach has basically been cookie-cutter, because that was the best we could do.

Today, if you are a man with Gleason 3 + 3 disease, depending on your age, general health, and a few other variables, you will most likely be told that you are a good candidate for definitive therapy – surgery or radiation; you might also be given the option of active surveillance.  If you have a strong family history of prostate cancer, if you are of African descent, you might be encouraged to get treatment sooner rather than later, and not to choose active surveillance.  But that’s about it; that’s the best advice we have for now, based on what we know about all of the men who have gone before you.

In a few months, in addition to the biopsy and PSA tests, you will most likely get a simple blood test to look for mutations in several known “bad apple” genes.  These are genes that do specific things to promote cancer, and there are drugs designed to target these specific genes.  “This is practice-changing,” says Simons, “it’s beyond extremely important.”

“Everybody talks about genes, but what really matters is, how does it help you?  How can it help your children and grandchildren?” -Jonathan W. Simons, MD

For example: today, if a man has a rising PSA, and it’s still fairly low, and a biopsy shows just a couple of cores of low-grade cancer, his doctor might want to wait and do another biopsy in six months to a year, and if it’s still inconclusive, the man might decide to get yet another biopsy in a few months.  But soon, that man will have a very important piece of extra knowledge to add to the puzzle.  “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, and “ignoring your genetic risk puts you at a much higher risk of dying unnecessarily.”  Take BRCA1 and BRCA2 genes, for instance:  “No woman should die from ovarian cancer if she’s a BRCA1 carrier, but after she has her kids she may need to have her ovaries removed to reduce her risk to zero,” as actress Angelina Jolie did.   It will be a similar situation for prostate cancer.

What Genetic Tests Mean For Me and My Kids? These “on the horizon” genetic discoveries, and the new tests that will result, have implications for the relatives – siblings, parents, children and grandchildren – of men who test positive for certain genes.  Your sons and grandsons may be at higher risk of getting prostate cancer.  Also important:  Your daughters and granddaughters may be at higher risk of developing colon, breast, ovarian, pancreatic, or other cancer. They also have different and important messages for men at every place on the prostate cancer spectrum.  For example: You don’t have prostate cancer, but your dad does:  Let’s say your dad has a genetic test and is found to have a gene that is linked to aggressive prostate cancer.  You need to have a blood test to look for cancer risk genes.  You also need to start getting screened for prostate cancer at age 40. You have been diagnosed with prostate cancer, and it seems to be pretty mild.  If a genetic test shows that you have one of the cancer risk genes, you should lean more toward aggressive therapy to get rid of the cancer, instead of active surveillance. You have advanced prostate cancer, or your PSA is rising after surgery or radiation.  If genetic testing shows you have inherited certain genes from either your mother or father, this could change your course of treatment, because some cancer drugs are already available that target specific genes.  Yours might be one of them. You have hormone-resistant prostate cancer, or metastatic disease.  If you have one of the genes known to respond to certain new cancer-fighting drugs, you might skip other kinds of chemotherapy and go right to a more specific, targeted treatment.

The startling finding with this new genetic testing is that it affects many more men than scientists had expected. New genetic research, funded by the PCF, has shown 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, “and that inheritance means more in prostate cancer than in any of the major cancers.”

The tests that are coming soon can show other things, too: They can identify certain genes that – if a man develops cancer—make it more likely that his cancer will be aggressive, and will require aggressive treatment.

Even if a man has what seems to be mild, slow-growing cancer, “he is at higher risk of developing another lesion that’s going to be worse,” Simons says.  Having one of these “predisposition genes” also means that “his children and grandchildren have the same gene, as well, and they deserve to know that their cancer risk is elevated.”  Some of these same genes are involved in other types of cancer; thus, if you have one of these genes, your daughter won’t need to worry about prostate cancer—but she might be at higher risk of getting breast, ovarian, or pancreatic cancer.

Because of this testing—it’s not here yet, but it will be commercially available within the next couple of years—genetic counseling will need to be part of the basic prostate cancer screening, Simons believes.

What does this mean for you?  Nothing right now.  But soon it will mean that if you have early prostate cancer and you have one of these mutations, you should not be on active surveillance.  It may mean that in addition to having surgery or radiation to remove your prostate cancer, you will also take a course of a drug that targets that specific gene, because that cancer is different from other cancers.  One such drug, called olaparib, targets BRCA-mutated cancer, and is already used to repair damaged DNA in ovarian cancer.

The test, says Simons, produces something that is “like a terrorist list.  These are master terrorist genes.”  The genes might not be the ones that cause cancer.  Again, having one 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 these genes 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.

Now you have a preview of the preview.  Over the coming months, as this research is published and the testing becomes more widely available, we will be able to tell you much more.

What Genetic Tests Mean For Me and My Kids? These “on the horizon” genetic discoveries, and the new tests that will result, have implications for the relatives – siblings, parents, children and grandchildren – of men who test positive for certain genes.  Your sons and grandsons may be at higher risk of getting prostate cancer.  Also important:  Your daughters and granddaughters may be at higher risk of developing colon, breast, ovarian, pancreatic, or other cancer. They also have different and important messages for men at every place on the prostate cancer spectrum.  For example: You don’t have prostate cancer, but your dad does:  Let’s say your dad has a genetic test and is found to have a gene that is linked to aggressive prostate cancer.  You need to have a blood test to look for cancer risk genes.  You also need to start getting screened for prostate cancer at age 40. You have been diagnosed with prostate cancer, and it seems to be pretty mild.  If a genetic test shows that you have one of the cancer risk genes, you should lean more toward aggressive therapy to get rid of the cancer, instead of active surveillance. You have advanced prostate cancer, or your PSA is rising after surgery or radiation.  If genetic testing shows you have inherited certain genes from either your mother or father, this could change your course of treatment, because some cancer drugs are already available that target specific genes.  Yours might be one of them. You have hormone-resistant prostate cancer, or metastatic disease.  If you have one of the genes known to respond to certain new cancer-fighting drugs, you might skip other kinds of chemotherapy and go right to a more specific, targeted treatment.

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Janet Worthington
Janet Farrar Worthington is an award-winning science writer and has written and edited numerous health publications and contributed to several other medical books. In addition to writing on medicine, Janet also writes about her family, her former life on a farm in Virginia, her desire to own more chickens, and whichever dog is eyeing the dinner dish.