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?” 

medical laboratoryA 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

mindless wanderingAn 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.

headacheSo 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

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Active Surveillance for Prostate Cancer

What You Need to Know

Is active surveillance right for you?  The answer to this question varies, depending on a bunch of factors: your particular form of prostate cancer, your age, and general health, and also on the criteria used to select men for active surveillance programs from hospital to hospital; some are stricter than others.

Men who are eligible for active surveillance have cancer that shows all signs of being the “good” kind:  slow-growing, low-volume (meaning, there’s not very much of it in all the tissue samples from your prostate biopsy), not aggressive. 

men thinkingCan men live with slow-growing, low-volume prostate cancer?  Absolutely.  The proof of this is found every day, in many thousands of autopsies done around the world, of men in their eighties and older who died of something else – a heart attack, for instance.  Then, in the autopsy, the pathologist looks at the man’s prostate and sees cancer in there.   This cancer is what doctors call “indolent.”  It’s low-risk.  Slow-growing, low-volume. It sits there.  It doesn’t cause any harm, and clearly never needed to be treated, because the guy never knew he had it and died of something else.  When urologist Christopher Barbieri, M.D., Ph.D., on the faculty at Weill Cornell Medicine at New York Presbyterian, talks to his patients who are candidates for active surveillance, he tells them, “You’re more likely to get hit by a bus when you’re 100 years old than for this cancer to kill you.”

Let us digress for a moment and think of prostate cancer in the form of an animal.  The most aggressive cancer is like a bird; it grows quickly and is very likely to fly away from the prostate to other places in the body, making it more difficult to kill.  The least aggressive cancer moves like – well, something slow, a turtle, or a sloth.  And then there are men with the cancers in between – let’s think of them as rabbits — cancers that do need to be treated with surgery or radiation.

Indolent prostate cancer is the pet rock of cancers; it doesn’t do much, but the upside of that is that it doesn’t need to be treated, either. 

Important point:  Cancer may not stay indolent.  Or, from the initial biopsy and test results it might appear to be low-risk and or low-volume, but actually more cancer is there and the biopsy needle just missed it.   So, men who choose active surveillance may not stay on it forever if their cancer undergoes “grade reclassification” – if that is, you have another biopsy and it suggests that more cancer is present, or that it may not be so slothlike in personality.  So if you choose active surveillance, know that at some point, you may need to have surgery or radiation.   If you are an African American man, talk to your doctor about getting an MRI to make sure that you don’t have cancer that was missed on the biopsy.

Choosing active surveillance – remember the keyword is “active” – means that you will need to keep getting your cancer checked out.  You will need to get follow-up PSA tests, exams, and biopsies, maybe once a year, for many years.  If you are a young man, say age 50, and you could reasonably expect to live another 40 years, this could mean that you get your prostate stuck with needles many, many more times in your life.  (Not until you’re 90, but at least another 15 years or so.)  Biopsies have their own risks, which I’ve written about here.  You may not want to subject yourself to this.

restaurant manYou will also have to live your life knowing you have cancer.  Can you handle this?  Some men can’t.  Thinking about the cancer in there makes them anxious.  To them, it’s like a time bomb – when actually, it may not be a time bomb at all, but more of a clock just happily ticking away, not causing harm – and they end up having surgery or radiation just for the peace of mind.

On the other hand, if you can live with it — trusting that the follow-up monitoring will detect any change if it happens and that if you need to get treatment, you won’t miss that window of treatment when the cancer is still confined to the prostate, and you will have plenty of time to make that decision — then active surveillance may be a good option for you. 

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

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Don’t Shun the Sun

sand_sun_beachIn 2002, when I ghostwrote the first edition of The Paleo Diet for Loren Cordain, I thought we were writing sacrilege when he said people need sunlight.  That’s because our view of what’s normal and natural has gotten skewed.  “Oh, no!” I thought.  “Must have sunscreen.  Sunscreen good, sun bad!”  Just a few steps away from Frankenstein being terrified of fire.

I’ve lightened up, so to speak, since then.  Cordain was right:  Yes, excessive sunlight exposure is linked to skin cancers, including squamous cell cancers, which form on the top layers of the skin; basal cell cancers, which form on the bottom layers of the skin; and melanomas, which form within the skin’s pigment-producing cells, the melanocytes.  However, avoiding sunlight is not the way to prevent disease.

“The experience of our hunter-gatherer ancestors proves helpful,” Cordain wrote.  “Many studies have shown that people with high lifetime sunlight exposure, similar to that of hunter-gatherers, have lower rates of melanoma than those with low sunlight exposure.  Also, indoor workers have a greater risk of melanoma than outdoor workers.  Even more puzzling, melanomas often arise in body areas that are infrequently or intermittently exposed to sun.”  Many scientists believe that severe sunburn during childhood — like that time where you went to the beach and came home red as a lobster, and maybe your mom (as mine did) treated it with baking soda and/or aloe, apple cider vinegar, or other home remedies — or intense burns in areas that usually don’t see the sun are bigger risk factors for the development of melanoma.

“When your exposure to sunlight is gradual, moderate and continuous,” Cordain explained, your body responds “in a manner guided by evolutionary wisdom.”  Your skin begins to get tan, because your body is ramping up its production of melanin.  The darkened skin helps protect you from the sunlight’s most damaging ultraviolet rays.  Also important: Vitamin D levels in the blood start to increase, too, as the UV light hits the skin and your body starts to convert cholesterol into Vitamin D.

Vitamin D is a really good thing.  It’s actually a hormone, which is mostly formed in the skin.  As an aside, jumping to other books I’ve co-written: In Dr. Patrick Walsh’s Guide to Preventing Prostate Cancer, Walsh, the noted Johns Hopkins urologist, points out that “over the last 25 years, the death rates from prostate cancer in America have been the highest in the regions of the country that get the least sunshine” (north of 40 degrees latitude).  However, Walsh cautions, taking too much Vitamin D is not a great approach, either.  If you’re going to take a Vitamin D supplement, he advises not taking more than 4000 IU per day.

Cordain cited evidence from population studies confirming that people with the greatest lifetime sun exposures have the lowest rates of prostate, breast, and colon cancers.  But most important to Cordain, from years of study of our Stone Age ancestors, is this: “Exposure to sunlight is natural for humans.  It is part of our evolutionary heritage.  Without sunlight, it is virtually impossible to achieve an adequate intake of vitamin D from the natural foods that were available to our hunter-gatherer ancestors.  Our food supply has been a significant source of vitamin D for a very short time — less than a century, when dairy producers began adding it to the milk and later, to margarine.  Sunlight exposure is healthy as long as it occurs in a slow, gradual, and limited dose over the course of a lifetime.”

©Janet Farrar Worthington

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Smokeless Tobacco: Move Your Chaw to Save Your Jaw

antique spittoon on floorIf you use smokeless tobacco, or know a guy who does and want to help him, this is for you.  Obviously, the best thing you can do is quit.  But if you can’t do that, these three words may save your life:  Move your chaw!

I’ll explain, with help from Jason Campbell, D.D.S., a Prescott, Arizona, dental surgeon who specializes in complex reconstructions.  (Note: Campbell is also a very nice guy, and he says if you have any questions about what we’re talking about in this story, contact him at frontoffice@myprescottdentist.com and he will answer them.)

When you stick a plug of tobacco in your mouth, it begins to break down, or denature, the tissue it touches.  It doesn’t just alter the tissue but the genetic code, as well, and this can lead to cancer.  By habit, says Campbell, “guys typically tend to keep the tobacco in the same spot all the time. “ The repeated chemical attack, of denaturant leaking out of a chaw of tobacco day after day, causes the body’s immune system to launch defensive countermeasures.   “The body’s way of protecting the tissue is, it toughens it up and thickens it, like when you get callouses on your hands from shoveling or lifting weights.  We see that wherever that tobacco goes.”  The official diagnosis of this phenomenon is called “tobacco pouch keratosis.”  (It’s gross.  Google it.)

Tobacco pouch keratosis is a precancerous condition.  “When the body starts laying excessive tissue down in order to protect itself, when those immune system cells get turned on, the body is automatically activating a system for cell formation.”  Cancer, Campbell points out, “is the continuous growth of tissue.  If the chemicals in tobacco alter the normal process, this system can get turned on and never turned off, and that’s when cancer can form.”  Usually, Campbell sees this keratosis on the lip and gum, but it’s kind of a tip-of-the-iceberg situation.  “Some of the fallout is, it creates inflammation in the area.  Periodontal bone loss is a process of inflammation, and that inflammation can cause a receding gum line, because it damages the bone, and then the gum follows the bone.  So periodontal defects are also very common in people who hold their tobacco in the same place over and over. “

If you smoke instead of chew, don’t feel too smug: The heat from a cigarette or cigar damages tissue, as well, and hampers the immune system in that area.  “So the heat is a problem, but the chemicals in smoked tobacco also inhibit the immune system,” says Campbell.  “Consider that the mouth is a pretty dirty environment.  A lot of different bacteria live there, and if the immune system is suppressed, it’s going to increase someone’s risk for bacteria-induced gum disease, as well as bacteria-caused tooth decay.”  (Another downside of smoking tobacco is that it messes up the taste buds; food doesn’t taste as good, and this suppresses the appetite – which is why you might see super-thin models and actresses puffing on cigarettes.  When people quit smoking, food starts to taste better.)

[Tweet “The damage to your lip and gum are reversible when you quit smokeless tobacco”]

Good news: the damage to the lip and gum is “100 percent reversible when tobacco products are discontinued.”  In the mouth, there is “a constant turnover rate of tissue replacement,” Campbell says.  “When the tissue detects that it doesn’t need to protect itself, that over-reactive thickening stops.  Usually that tissue can rebound.”  Periodontal damage, and damage from bone loss, can be corrected with surgery.

If you can’t quit chewing tobacco, there is still good news:  “I encourage our patients, if they are unwilling to quit, to move it.  My job as their dentist is to help them avoid big problems.  I’d much rather have them move it than increase their risk for cancer.”  For example:  If you generally keep your chaw tucked away on the right side of your mouth, put it on the left.

Campbell knows that for a lot of people, this means, “I just reduced my risk for cancer.  It’s okay for me to continue to chew!”  So, just because you can minimize your risk of cancer by moving your chaw, don’t think that’s one more reason why you shouldn’t quit.  “But one upside is, seeing that tissue heal does bring peace of mind for people.” It doesn’t happen right away, but “in six to eight months, we usually see that kind of leathery tissue start to dissipate.  In the tissue where there is receding of the gum, almost instantly we see the inflammation go down.  The gum is usually red and inflamed there, and that will heal very quickly.”

Keep in mind, Campbell notes, that tooth decay and gum disease are bigger oral health worries than the risks of cancer when it comes to smoking or chewing tobacco – and quitting reduces your risk for having to get cavities fixed, having your teeth go bad and needing crowns, or needing to have gum surgery.  “People need to understand that their risk of developing oral cancer is low.  But their chance of survival is very low.”  The mouth has a lot of blood flow – blood that can take cancer elsewhere, allowing it to metastasize.  People who get oral cancer from tobacco may need to have part of their face removed, or may risk having that cancer spread to other parts of the body.   I wouldn’t wish that on anyone.

Rinse Tests for Oral Cancer:  “We’re getting better at detecting oral cancer,” says Campbell.  Most dentists now check your mouth and throat very carefully for tissue changes, and at many practices, you can request a diagnostic test for oral cancer – a fluorescent rinse that bonds with precancerous cells, causing them to glow or stand out when the dentist shines a light on them.  These tests look for abnormal tissue, and aren’t just limited to changes caused by tobacco.  They can also detect other oral cancers, such as those caused by HPV.

©Janet Farrar Worthington

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