, , ,

Worried About Prostate Cancer?  Be Proactive! Part 2: Exercise and Key Foods

Recently for the Prostate Cancer Foundation (PCF), I interviewed two scientists who study lifestyle factors and their effect on prostate cancer:  Epidemiologist June Chan, Sc.D., of UCSF, and epidemiologist Lorelei Mucci, M.P.H., Sc.D., of Harvard.  In the last post, we talked about diet.  Now let’s look at exercise, and we’ll wrap up with some quick takes on various foods.

Here’s some good news:  By launching your proactive strike against prostate cancer, you’re not just helping your prostate (or helping to keep cancer from coming back, if your prostate is long gone):  You’re helping your heart, and you’re also helping to lower the risk of diabetes and insulin resistance.  Go, you!

A sedentary life is not good for the heart.  Diet is important, but it’s not the whole story here.  The research team of June Chan at UCSF has shown in multiple studies that exercise can help delay or prevent prostate cancer progression.  “Aerobic exercise after prostate cancer diagnosis may reduce the risk of prostate cancer recurrence or death by 60 percent.”  Chan’s earlier studies in this field, funded by PCF nearly a decade ago, showed a benefit to an hour of jogging six days a week – the level of exercise most of us can’t or don’t want to sustain.  But don’t get discouraged!  In more recent studies, she and colleagues have been looking at more doable levels of exercise – walking 30 minutes a day, or three or more hours a week, at a brisk pace (3 mph or faster).  The brisk pace is important:  One study found that men who walked three or more hours a week after diagnosis had a 57-percent lower risk of having prostate cancer recur than men who walked at a slower pace, for less than three hours a week.

“Just walking, not running!  Walking is so common.  During these Covid times, when we’re confined to small spaces, people might find it difficult to walk the way they would prefer,” says Chan.  “But I would say, just use it as a break to get fresh air – even if you’re just going up and down the same block.  Any little bit of walking, as opposed to sitting.  Movement is good for your overall bone health.  Don’t push yourself to injury; just get in a good habit.  It’s something you can do when you’re doing something else;” for example, “when I’m walking, often I’ll grab my phone, and use it as a chance to catch up with somebody.”  Don’t focus on the number of steps, or the time.  “If you’re always looking at your watch, you’re not enjoying the walk as much.”  And don’t overdo it:  “If you get injured, you might lose all interest in continuing.”

Note:  the key here is giving the cardiovascular system a good workout, not necessarily the act of walking itself.  So, apply this to your own needs:  if walking that much is not a good option for you, swimming and riding an exercise bike – whatever you are able to do – are good, too.  Studies by Chan and others have provided so much proof of the benefit of aerobic activity, in fact, that “we’re actually at the stage now that the updated Physical Activity Guidelines put out by the American College of Sports Medicine specifically note that exercise is recommended for men with prostate cancer to avoid the risk of dying from prostate cancer.  We’re really excited that we got to contribute to that work.”

What is it about exercise?  Chan and colleagues are still tapping the surface of all the ways exercise is good for the body.  “It improves energy metabolism, lowers inflammation and oxidative stress, helps boost immunity, and is beneficial for androgen signaling pathways.”  It is good for the heart and lungs, improves muscle strength and muscle mass, burns fat, lowers fatigue, anxiety, stress, and depression.  “It just improves your overall quality of life,” says Chan.  Bonus:  exercise also may help slow down prostate cancer’s growth.

Chan is investigating the underlying biological mechanisms for “why exercise has these benefits for prostate cancer and overall health.  Is it a systemic effect, or an anti-androgenic effect?  Is it acting on oxidative stress pathways?”  Her group is looking for insight from blood and tissue samples taken from men with prostate cancer before and after exercise interventions.  In another large, phase 3 clinical trial funded by Movember, Chan and epidemiologists Stacey Kenfield and Lorelei Mucci, with principal investigators Rob Newton and Fred Saad, are studying high-intensity exercise in men with metastatic prostate cancer, at more than a dozen sites worldwide. “It’s a two-year, tailored intervention, with both strength and aerobic components,” to see if exercise can help men with metastatic prostate cancer live longer and better.  What else lowers stress?  Meditation.  Stress may play a role in the growth of prostate cancer, so lowering stress is a strategy worth pursuing.

Speaking of strength training:  We all lose muscle mass as we get older.  Strength training (lifting weights or using resistance bands, and doing muscle-building exercises) fights this loss.  Strength training can be especially helpful in men on androgen deprivation therapy (ADT) for advanced prostate cancer, who are at higher risk of loss of muscle mass, osteoporosis, and also of weight gain, metabolic syndrome, and diabetes.  Note:  If you have advanced prostate cancer, check with your doctor to make sure strength training is safe, and also for some guidance about the weights you should be lifting.

Final note on exercise:  Start out slow.  “If you have not exercised regularly for a long time, consult with a physician or personal trainer, to get a program tailored to fit you,” says Chan.  “Start small, and go up by five- or ten-minute increments.  Then see if you can pick up the intensity.  Just make little changes.”

Look to the long haul:  “Thank goodness I ate that broccoli on Thursday.  Now I won’t get prostate cancer,” said no one ever.  It’s not just one good food choice, but many years of erring on the side of healthy.  The other side of that, however, is reassuring:  It’s not just one bad food choice, or being a couch potato last weekend, but many years of not eating things that can help your body fight prostate cancer, many years of not exercising.  “Diet is something you have to do every day,” says Chan.  So is exercise.  That said, “we’re all balancing so many things with food.  Food is part of our culture, taste, our family habits, celebrations.  I feel like the recommendations should just be like filters.”  In other words: many good decisions, over time, will help fight prostate cancer more than the occasional lapse will help promote it.

 

Thumbs Up, Thumbs Down:  Quick Takes on Food

            I asked Lorelei Mucci for her expert opinion on some foods you may be wondering about for their cancer-fighting powers.  Here’s the rundown, in no particular order:

Extra virgin olive oil (EVOO):  Yes!  More than 2 tablespoons a day.  Among other things, EVOO contains hydroxytyrosol, which scientists now recognize as a natural means of cancer chemoprevention.  It is a powerful antioxidant, and it has been shown to protect against cancer by slowing proliferation of tumor cells and increasing apoptosis – “suicide” – of cancer cells.

Tomatoes:  Yes!  Especially when cooked in, or drizzled with, olive oil, which helps you absorb a key component of tomatoes, lycopene.  “The prostate accumulates a lot of things,” including cholesterol.  “It accumulates lycopene.  When a man eats a diet high in lycopene, for some reason, lycopene levels in the prostate go up.  Lycopene makes sense biologically, because it does accumulate in the prostate.  It is an antioxidant.  This is one of the individual dietary components that seems pretty promising.”

Don’t like tomatoes?  Good news:  Lycopene is in watermelon and grapefruit, too!

Coffee:  “Coffee is looking more and more promising .  There are now a number of studies that suggest drinking coffee regularly, one to two cups a day, can help prevent aggressive forms of prostate cancer.  Some studies say three to four cups offer even more of a benefit, but there’s an initial benefit with one to two cups.  Coffee may also lower the risk of diabetes, liver cancer, and Parkinson’s disease.”

Tea:  Sure, what the heck.  There are far fewer studies on tea than on coffee, but tea has antioxidants.  People in Asia, which has less prostate cancer than the U.S., drink a lot of green tea.  “Tea lowers inflammation, but has not been shown to have an effect on insulin levels.”  However, and this is important:  it doesn’t seem to raise your risk of getting prostate cancer.

Note:  If you go to a fancy coffee shop and get a 1,500-calorie coffee with not only cream but whipped cream, and loads of sugar, or if you drink a super-sweet tea loaded with sugar or high fructose corn syrup, the effects on insulin resistance and risk of weight gain will probably cancel out the antioxidants.

Fish:  Yes.  “We published a meta-analysis of epidemiologic studies that looked at fish and prostate cancer death, and there was a pretty good benefit with regular consumption of fish.”  Particularly “dark-meat” fish rich in omega-3 fatty acids, like salmon and red snapper.

Devil’s advocate:  Are men healthier because they eat fish, or because if they choose fish, they’re not eating a big old ribeye steak cooked in butter?  Talk amongst yourselves, but fish is not nearly as pro-inflammatory as red meat.

Nuts:  Sure.  “There’s not much evidence one way or another with prostate cancer death, but they really seem to lower the risk of cardiovascular disease and overall mortality.”  Also, if you’re eating a handful of nuts as a snack, maybe you won’t be eating a bag of chips.  “In one of our studies,” says June Chan, “we observed that substituting 10 percent of calories from carbohydrates for calories from healthy, plant-based fat (nuts) was associated with a 29-percent lower risk of prostate cancer death, and a 26-percent lower risk of all-cause death.”

Pasta:  In moderation.  However, non-traditional pastas, made from cauliflower or chick peas, are another way to sneak in vegetables.  They may also help you manage your weight.  “Excess body weight, particularly the visceral fat around the abdomen, is associated with worse outcomes from prostate cancer.  Anything men can do to help reduce their weight – limiting bread and pasta, and increasing things like cauliflower pasta and vegetable intake – is beneficial.”

Charred meat:  Try to limit it.  When food is charred, it makes a chemical compound called PhIP, that is a known carcinogen.   Even worse: those beautiful (charred) grill marks combined with a pro-inflammatory food, like red or processed meat.

Soy:  sure.  “Consumption of soy is much higher in Asia, where the incidence of prostate cancer death is lower.  Soy is probably part of a strategy for maintaining healthy weight, and it’s a way of replacing red meat.  Does it lower prostate cancer death?  I don’t know that we have that evidence.”  Another complicating factor:  “Men who eat more healthy diets tend to get screened for prostate cancer.  If you get regular PSA testing, you’re five times more likely to get diagnosed with prostate cancer.”  And, if you get diagnosed early, you are more likely to get early treatment while the disease is confined to the prostate.  It’s like the children’s book, If You Give a Mouse a Cookie, a domino effect.

Vitamin D:  Yes.  “There’s really promising data on vitamin D and prostate cancer mortality.”  One randomized trial, the VITAL study, showed “specifically in black men who have low levels of vitamin D, there’s a reduction in prostate cancer mortality.  Evidence from many studies suggests that this makes sense; there’s a lot of genetic data on inherited vitamin D pathways; this pathway seems to be very important for prostate cancer.”  Vitamin D is found in some foods, such as fatty fish and egg yolks, and your body makes vitamin D when you get out in the sunlight.  However, most people don’t have sufficient levels of vitamin D.  Thus, your best strategy is to take a vitamin D3 supplement:  2,000 IU daily.  It’s not a case of “more is better.”  2,000 IU is what you need.

Final thought on food:  In the words of the title song on Al Jarreau’s 1977 breakthrough album:  Look to the Rainbow.  Build your diet around an array of colorful, plant-based fruits and vegetables: green, red, yellow, orange and purple.  Those colors reflect the good nutrients in them.  Eat less red meat, and have restraint with sugar and carbs, and go for EVOO instead of butter.

In addition to the book, I have written 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

 

 

 

 

 

 

 

 

/0 Comments/by
, , , ,

Worried About Prostate Cancer?  Be Proactive! Part One

Part One:  Live Your Best Life!

What can you do to live your best life?  You might say, quite reasonably, that your best life does not include prostate cancer.  True.  But no matter where you are in your journey – prevention, treatment, recovery, or survivorship – what can you do to maximize the good, to help your physical and mental wellbeing?  There’s actually quite a lot!

For example: Exercise not only helps you lose weight; it helps fight depression, and it even can help slow down prostate cancer!  And eating the right diet – as opposed to eating a lot of junk and chemicals – can boost your spirits, your energy level, and just generally make you feel better.  Even better:  it can help lower inflammation and insulin, and this can help your body fight prostate cancer, and can help prevent diabetes, cardiovascular disease, and other chronic illnesses.

There is growing evidence that the lifestyle choices that help prevent or fight other diseases – like, eating low sugar for diabetes, or exercising for your heart – can also help prevent or slow down prostate cancer.

Here are three basic principles:

What lowers inflammation helps fight prostate cancer.

What fights diabetes and insulin resistance helps fight prostate cancer.

What is good for the heart is good for the prostate.  We will cover all of this here and in part two.

Studying Diet is Hard

For the Prostate Cancer Foundation (PCF), I interviewed two scientists who study lifestyle factors and their effect on prostate cancer:  Epidemiologist June Chan, Sc.D., of UCSF, and epidemiologist Lorelei Mucci, M.P.H., Sc.D., of Harvard.

Right off the bat, both of these experts note that studying food is hard, and the answer to staying healthier is not one single thing.  There is no dietary magic bullet, and if you see one advertised and choose to take it, do so with a huge proverbial grain of salt!  In many studies over the years, scientists have tried to isolate specific foods to see if they promote or prevent cancer – but they did it by asking people to recall what they ate over certain periods of time.  And most people don’t have ideal memories:  “Yes, I ate that fairly regularly.  No, I didn’t eat this – wait, maybe I did.”  See the difficulty?

Okay, so what if people keep a food journal?  That’s more helpful, although these kinds of studies, done right, take many years.  Even then, if you isolate certain foods that seem promising, you still don’t know exactly what’s happening!  Let’s say you are studying what people eat and you notice a trend in those who didn’t get cancer:  they eat apples (hypothetically).  What kind of apples?  Is it all apples, or just Granny Smiths?  Were they all grown in the same type of soil?  Were they cooked, or eaten raw?  Peeled or not?  Organic or not?  How many did people eat a day?

But wait!  Did these people even have an actual benefit from eating the apple – say, one they brought to work from home – or did they benefit from not eating a bag of cheese puffs or Twinkies from the vending machine instead?

And wait some more!  Do the people who benefited have genetic or molecular differences that make them more likely to be helped by apples?  Or… are people who eat apples also more likely to exercise and take better care of their health in general – so maybe it’s not even the apples but their whole lifestyle that made the difference, and we’re back to the drawing board!

This is why science around nutrition takes time.  Remember back in 2010 when coffee was bad?  And now, here we are in 2020 and coffee is good?  This stuff evolves.  The good news is, we’ve learned a lot.

Broad Strokes are Better

Scientists don’t have a Paint-by-Number approach to food science, with every single food accounted for.  But they are able to paint with broad, but definitive, strokes.

In our interviews, June Chan and Lorelei Mucci both cited work led by Harvard scientists Fred Tabung, Ph.D., M.S.P.H., and Edward Giovannucci, M.D., Sc.D., that look at the relationship between diet and inflammation.  In one, the scientists tracked inflammatory markers in the blood and whether inflammation was raised or lowered by what people ate, based on data from thousands of participants in the Nurses’ Health Study and the Health Professionals Follow-Up Study.  The key for us is the foods they found that reduce inflammation:  dark yellow vegetables (carrots, winter squash, sweet potatoes, etc.); leafy green vegetables (like spinach, broccoli, kale, etc.), coffee, and wine.  Beer (one bottle, glass, or can) was in this category, too.  So was tea, but its effect was not very strong.

The pro-inflammatory (bad) category, included processed meats (hot dogs, bacon, pepperoni, lunch meat, etc.), red meat, refined grains, high-energy beverages (with additives and sweeteners), and “other vegetables,” like potatoes and corn.  Interestingly, not all fish is equal:  canned tuna, shrimp, lobster, scallops, and “other” fish were more inflammatory than “dark-meat” fish like salmon or red snapper.

But if you love canned tuna, and if you love a baked potato or corn on the cob, don’t freak out:  remember, broad strokes!  The key seems to be to make sure you do eat the anti-inflammatory foods.  For example, the anti-inflammatory effects of leafy green vegetables, dark yellow vegetables, wine and coffee are more powerful than the very mild, pro-inflammatory effect of “other fish” or “other vegetables.”  If you feel that you just can’t give up meat entirely, that’s okay – just aim for smaller portions of meat, surrounded by anti-inflammatory vegetables.  Example:  instead of regular fries, try sweet potato fries.  They’re really good, and they fight inflammation!  You can have your burger, but still help counteract inflammation:  it’s a win-win!

So:  what about foods that are bad for diabetes and insulin resistance?  Tabung and Giovannucci led another study, also using data from the thousands of participants in the Nurses’ Health Study and Health Professionals Follow-Up Study, to assess the “insulinemic potential” of diet and lifestyle – basically, how foods and exercise affect blood sugar and insulin resistance, as measured by certain biomarkers in the blood.  Foods that did not raise blood sugar or insulin resistance included wine, coffee, whole fruit, high-fat dairy (whole milk, sour cream, a half-cup of ice cream, a slice of cheese, etc.), nuts, and leafy green vegetables.  Physical activity was also good for lowering insulin resistance and blood sugar.

What do the experts make of this?  Benjamin Fu, a postdoctoral fellow in Lorelei Mucci’s lab at Harvard has been looking at these two different dietary patterns: “a diet associated with hyperinsulinemia, and a hyper-inflammation diet.”  The two diets have some overlaps, but are not identical.  Neither is good for men worried about prostate cancer, Mucci says, “particularly the hyper-insulinemia (blood sugar-raising) diet, which is associated with a 60-percent risk of more advanced or fatal prostate cancers.”  Let’s just let that sink in for a second:  if you eat a lot of carbs and sugar and you get prostate cancer, you’re more likely to have a serious form that could kill you.  Okay, let’s go on:

Mucci continues:  “The hyper-inflammatory diet also is associated with an increased risk of prostate cancer,” particularly in men who develop cancer at a younger age, in their forties and fifties.  “It may be that earlier-onset cancers are more susceptible to the effect of diet and lifestyle.”

What does heart health have to do with it?  A lot, for many reasons.  It turns out, says Mucci, that “cardiovascular disease and other chronic diseases are the major cause of death in many men who have prostate cancer.  If you look at men with localized prostate cancer and survival outcomes over 10 years, three-fourths of the deaths in those men will be due either to cardiovascular disease or another chronic disease.  Only one-fourth of the mortality is due to prostate cancer.”  Now, you may be thinking, we all have to die of something, right?  This is true, but “these men are dying sooner than they should, and eating a plant-based diet rich in cruciferous vegetables will help lower that risk of cardiovascular disease.”

Which brings us to the Mediterranean Diet:  Not only do people in Mediterranean countries, as compared to Americans, eat more vegetables and fruits, fewer fatty foods, less processed junk, and less red meat – “which increases insulin resistance, increases inflammation, raises cardiovascular risk and also is part of a dietary pattern that may increase obesity, as well,” as Mucci notes.  You know what else they eat a lot of?  Olive oil.  Greater than 30 ml a day, which is a little over two tablespoons.  “There’s really good evidence that extra virgin olive oil (EVOO), either on its own or as part of the Mediterranean diet, substantially lowers the risk of cardiovascular disease and lowers the risk of overall mortality.  The evidence specifically for men with prostate cancer is much more limited, but given the strong benefits for overall death and cardiovascular death in particular, not only using EVOO, but using it to replace butter or margarine, is something that is worth doing.”

 

Coming up:  Part 2:  What’s Good for the Prostate is Good for All of You!


In addition to the book, I have written 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

 

 

 

/0 Comments/by
, ,

Could Anti-Inflammatory Drugs Work Against Prostate Cancer?

If, as we have seen, inflammation can lead to prostate cancer, could anti-inflammatory agents help protect against it?

The jury’s still out.  However:  Johns Hopkins epidemiologist Elizabeth Platz, Sc.D., has been intrigued by this possibility for many years.  She is senior author of a new study on the use of aspirin and statins, published in Cancer Prevention Research.  The study, of men in the placebo arm of the Prostate Cancer Prevention Trial, doesn’t answer this question once and for all – but adds more weight to the idea that, for lowering the risk of developing potentially fatal prostate cancer, fighting inflammation is a good thing.

Evidence from observational studies has suggested that when taken regularly over time, aspirin may lower the risk of prostate cancer.  These drugs block enzymes that play a key role in the body’s inflammatory response.  Other studies have linked long-term use of statins, prescription drugs that are used to lower cholesterol but that also are anti-inflammatory, to a lower risk of advanced and metastatic prostate cancer.

In this most recent study, the investigators looked for inflammation markers in benign prostate tissue samples.  “We compared the use aspirin and statins with the presence and extent of inflammation in the prostate tissue,” says Platz.  They also looked at prostate biopsy slides for the presence of certain immune cells that are involved in inflammation.

“Of 357 men, 61 percent reported aspirin use, and 32 percent reported statin use,” Platz continues.  “Aspirin users were more likely to have low FoxP3, a T regulatory cell marker, and statin users were more likely to have a low CD68, a macrophage marker.”  “Our results suggest these medications may alter the immune environment of the prostate. A next step is to determine whether these immune alterations may underlie the epidemiologic observations that taking an aspirin or statin may protect against getting advanced prostate cancer, and dying from it.”

Prostate Cancer Loves Fats          

Here’s some more recent research out of Johns Hopkins, a neat bit of  basic science that may help explain the findings of Platz’s recent study:  “Our work is mechanistic,” says investigator Marikki Laiho, M.D., Ph.D., director of the Division of Molecular Radiation Sciences, “and provides insight into how the tumor microenvironment senses the excess load of the lipids.  Diet and statins obviously relate to the amount and regulation of the lipids, and have shown those clear correlations to prostate cancer.  However, we need to understand why to be able to correct the problem. Our work provides at least one explanation how the lipids fuel cancer. One part of the work was just to feed the prostate cancer cells with cholesterol, which made them more invasive.”

It turns out that even on a cellular level, prostate cancer gravitates to its own kind of junk food – the tiny version of deep-fried Oreos with a side of chili cheese fries.  Laiho and colleagues have just figured out how the body enables prostate cancer’s terrible diet.

The culprit is a lipid-regulating protein called CAVIN1, the scientists reported in the journal, Molecular Cancer Research.  In lab studies, when CAVIN1 was removed from cells in and around the prostate tumor, the fatty acid that was in those cells spilled into the tumor’s microenvironment.   The effect on prostate cancer cells was dramatic:  the cancer cells soaked up the lipids, which then acted as turbo fuel to make the cancer spread more aggressively.

“In every prostate cancer cell line we tested,” says research fellow Jin-Yih Low, Ph.D., the study’s first author, “tumor cells universally had an appetite for the lipids, using them to strengthen the protective membrane around the cell, synthesize proteins and make testosterone to support and fuel the cancer’s growth.  The tumor cells then behaved more aggressively, exhibiting invasive and metastatic behavior.  Just having access to the lipids gave the tumor cells more power; the tumor’s behavior changed.”

But wait!  There’s more:  nearby cells changed, too.  Deprived of their lipids, normal stromal cells started to churn out inflammatory molecules, adding fuel of their own to the fire. 

Laiho’s team then confirmed their findings in mouse models, comparing tumors with and without CAVIN1 in the stromal cells.  In the mice, Laiho says, “although the presence or absence of CAVIN1 did not affect the speed of tumor growth, lack of CAVIN1 definitely caused the cancer to spread.  All of the mice with tumors that lacked CAVIN1 had a twofold to fivefold increase in metastasis.  The tumors also had a fortyfold to hundredfold increase in lipids and inflammatory cells.”

The investigators were surprised at these results, Laiho adds.  “We suspected CAVIN1 was important, but we didn’t realize how important.  The tumor’s microenvironment matters, and the amount of lipids matters a lot.”  Just changing the level of lipids “created a situation of rampant metastasis.”

What could come from this research?  One possibility is development of a new biomarker:  a loss of CAVIN1 in local or locally advanced cancer, for example, could signal a higher risk of metastasis.  The next step is to understand more about the inflammatory process in the tumor’s microenvironment.  “We want to understand why the inflammation brings in macrophages, immune cells that further exacerbate the inflammatory process, instead of T cells, which should attack the cancer.”  The more scientists know about how inflammation does its nasty work to inflame cancer, the closer we are to finding a way to stop it.

 

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

/0 Comments/by
, ,

Infection, Inflammation, and Prostate Cancer

Why does it matter if you eat right and exercise?  Everybody knows the answer; in fact, we’ve all heard it so many times, it’s easy to tune it out:  diet and exercise are good for you.  Duh!  Who’s going to argue with that? Having a healthy lifestyle is right up there with world peace as a worthy goal!

Bear with me here:  With a topic such as this, I know I’m either preaching to the choir – people who are already exercising and eating a pretty good diet – or I run the risk of turning off the people I really want to hear this message, by seeming to preach at all: people who might think, “Go ahead, tell me what to do.  I really enjoy that.  Micromanage my life.  Maybe you’d like to come over and look at my closet and tell me what shirt to wear today.”

Okay, fine!  I’m not here to tell you what to do.  But I am going to try really hard to tell you why you might want to do certain things, and how good diet and exercise – or the lack thereof – can affect prostate cancer.

Please pardon the long set-up, but let’s begin with some facts, with plenty of links for further reading:

If you exercise, you are less likely to have cancer return after treatment, less likely to get metastatic prostate cancer and die of it.  What does exercise do?  A lot of good things for your vascular system, which, in turn, can help slow down prostate cancer metastasis.  But you know what it also does?  It helps you lose weight.

And it just so happens, men who lose weight are less likely to die of prostate cancer.

And sugar can make cancers grow faster.

And men who stop smoking are less likely to have cancer come back after treatment, and less likely to die of prostate cancer.

Exercise also helps control stress, and the stress hormone, cortisol, affects adrenal receptors, and can play a role in making cancer grow and spread faster.

Now, here’s why all this matters so much:  smoking, not exercising, quaffing sugary drinks, eating processed, fatty foods, and being overweight all contribute to inflammation.

I’m going to be writing a lot about inflammation in the next few posts, because it is becoming increasingly evident that inflammation can lead to cancer – and it’s quite possible that if we can prevent inflammation, we may prevent or at least slow down cancer.

What Inflammation Does

In a landmark study, Karen Sfanos, Ph.D., and scientists at Johns Hopkins have shown for the first time that bacterial infection can cause prostate cancer.  The study was led by Sfanos and her former graduate student, Eva Shrestha, Ph.D., in collaboration with Angelo De Marzo, M.D., Ph.D., Jonathan Coulter, Ph.D., and colleagues.  Infection? That’s not the same as inflammation!  True… but bear with me.

The bacterial culprit found in this study belongs to the family Enterobacteriaceae, which includes E. coli. Better known as a nasty gastrointestinal bug, E. coli causes inflammation in the urinary tract and is a known cause of bacterial prostatitis.  As the scientists discovered, colibactin, a genotoxin produced by some strains of E. coli, can also instigate a series of unfortunate events in the prostate.  Bacterial infection leads to acute and chronic inflammation, which can lead to the development of a lesion in the prostate called proliferative inflammatory atrophy (PIA), first described by pathologist De Marzo, oncologist William (Bill) Nelson, M.D., Ph.D., and other Johns Hopkins scientists; it can also cause DNA damage. The presence of colibactin is even more ominous, because it can directly lead to double-stranded DNA breakage. 

Sfanos suspects that this combination leads, in turn, to another development:  fusion of two genes, TMPRSS2 and ERG, that normally should remain separate, but in this case get abnormally spliced together.  Now, it may be that by themselves, TMPRSS2 and ERG are like Robert Leroy Parker and Harry Alonzo Longabaugh:  put them together, and they became Butch Cassidy and the Sundance Kid, and together, they got into much worse trouble than either one managed alone.  This TMPRSS2/ERG fusion – found in as many as half of all prostate cancers – is thought be an early event leading to the development of prostate cancer.

“We found evidence in human tissues (from prostatectomy specimens) that bacterial infections are initiating the TMPRSS2/ERG fusion,” says Sfanos.  “We don’t think this is the only way bacterial infections contribute to cause prostate cancer.  But in this particular study, the way we looked at it was by tracking the presence of these TMPRSS2/ERG fusions.”

It is entirely possible, notes De Marzo, “that other types of mutations or events could also be caused by bacterial infections or inflammation.  But looking at these fusions gave us ‘smoking gun’ evidence that bacterial infection was the initiating event.”  Sfanos adds that “the colibactin-producing bacteria, TMPRSS2/ERG fusions, PIA, and tiny buds of cancer were all there, in the same place at the same time, a snapshot of prostate cancer being born.”  The team’s early findings are available online in BioRxiv, a scientific data-sharing website, and a manuscript for publication is undergoing peer review.

Bacterial infection is a known cause of other cancers.  H. pylori, for example, is a well-established cause of stomach cancer.  “We believe that many different types of microorganisms, certain types of sexually transmitted infections (STIs), and other infections in the prostate can certainly cause the same chain of events,” says Sfanos.

How did the bacteria get into the prostate?  They could have come from the urethra.  “These bacteria are good crawlers,” Sfanos says.  De Marzo recalls what the late Don Coffey, Ph.D., the longtime director of the Brady’s scientific labs, used to say: “The urethra is like the Holland Tunnel for bacteria.”

Note:  These tiny cancers are not the cancers that were biopsied and that led to the diagnosis of prostate cancer; they’re too young even to achieve a Gleason grade.  They’re just baby sites of cancer cropping up, in addition to the more mature cancer that was already there.  Prostate cancer is multifocal:  in most men with prostate cancer, several sites of cancer develop at the same time.  But because of the unique molecular tools used in this study – looking for TMPRSS2/ERG fusions and “ERG-positive PIA” – Sfanos, De Marzo and colleagues were able to catch the formation of these invasive cancers in real time.  “This might start to explain the multifocal nature of prostate cancer,” says Sfanos. “There might be multiple infections or other inflammatory events that occur throughout a man’s lifetime.”

Sfanos suspects that the men whose tissue was used for this study “likely all had undiagnosed infections.”  These findings may lead to development of a new test, using urine or prostatic fluid, to look for colibactin or markers of inflammation in the prostate.  Future studies may look at urine samples along with prostate tissue for such markers, and  new imaging technology may one day be able to detect inflammation, as well.

For more than 20 years, De Marzo and Sfanos, with Brady scientists Bill Nelson, Srinivasan Yegnasubramanin, M.D. Ph.D., Elizabeth Platz, Sc.D., and William Isaacs, Ph.D., have studied inflammation as a risk factor for prostate cancer, particularly looking at PIA.  Sfanos “has also been the major champion of infection” as a risk factor, De Marzo says.  Now, these two paths of investigation have come together.

Could dietary changes make a difference?  “Bill Nelson showed years ago that loss of expression of the GSTP1 gene rendered prostate cells more susceptible to DNA damage caused by a chemical compound that is found in charred meat,” says De Marzo.  “Infection plus a bad diet might make this worse, and then combine that with the underlying genetics.  There might be multiple culprits, a constellation of things over years.”  We’re going to look more at diet in future posts.

Coming up next:  Could anti-inflammatory drugs help?

 

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

/0 Comments/by
, , ,

How Inflammation Sparks Prostate Cancer

Believe it or not, there once was a time when the Grand Canyon was just a ditch.  Before that, it was a rough patch in the desert with a river running through it.  It took a very long time for that canyon to form, and the conditions had to be just right to allow water, blazing sun and wind to chip away through layers of fragile rock.

On a very much smaller scale, this is what happens to cause cancer when the conditions are just right.

Now, if you will:  While we’re thinking about the Grand Canyon, let’s pan the camera a few miles away. We’re near some tall pine trees, and there’s a campfire.  Some cowboys are sitting around it.  Let’s imagine that they all have white hats; they’re good guys.  (They’re also much quieter than the cowboys around the campfire in “Blazing Saddles,” so don’t go there!)

If you’ve ever sat around a fire, you know that wood sometimes pops unexpectedly and sends out sparks.  That’s exactly what happens at our little campfire, and it happens to hit one of the cowboys square on the arm.  He brushes out the sparks, then goes back to his seat.  Nothing’s really changed; he laughs it off.

Wouldn’t you know it, the fire sparks up again – right on that same poor guy.  This time, he’s a little more scorched; his shirt has a hole in it and his eyebrows got singed.  He’s also a little irritated.

It happens a few more times, and he is no longer the proverbial happy camper.  He’s moving around, no longer sitting quietly, he’s got some burns that will leave scars, and he’s angry.  His hat is so charred now that it’s almost black.  One last spark, and he’s out of there.  He leaves the campfire, saddles up his horse, and rides away, fighting mad and looking for trouble.

This little scene plays out a lot, every day, in our bodies.  There are countless campfires – like stars dotting the sky – that flare up, burn quietly, get snuffed out, and never cause harm.  The campfires are little flares of inflammation.  

Commenting on this analogy is medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation.  “The future of fighting prostate cancer,” he says, “is either to stop the sparks from flying, or to put fire retardant on the flames – or better yet, to bring in the fire retardant really early in life.  It’s all about the sparks, and what makes the sparks, and then spark interception or spark interdiction.”

Expect to Hear a Lot More About Inflammation

Inflammation is our own version of Dr. Jekyll and Mr. Hyde: When it works the way it’s supposed to – when you skin your knee or get a paper cut on your finger, for instance – inflammation is what protects your body from bacteria and germs that find their way through the open wound.  The immune system kicks in; zealous home soldiers like killer T cells spray chemicals on the intruders, puncture their armor, or even eat them whole.  You notice some redness, a little heat, maybe some swelling or even a bruise, and you know that your body is healing.  There’s a scab, new skin covering the hole or tear, and all is well. The inflammation goes away.

But what if it doesn’t go away?   Here’s where the dark side of Dr. Jekyll, his alter ego Mr. Hyde, starts to show itself.  Chronic inflammation is bad.  

“The story of inflammation is absolutely the heart of what causes prostate cancer,” says Simons.  “Inflammation lowers your defenses,” and changes the DNA.  Going back to the angry cowboy at our campfire scene: If only he had moved away from the fire, or if someone had poured a little water on the fire to cool it down and keep the flames low.  He might have had a few scars, but he would have been okay.  Instead, he began moving around, and eventually he left the campsite; if he were a prostate cell, he would have become cancerous – but still there at the site, still easily treatable.   But as he became more scorched, he became metastatic.  The continued exposure to those flames turned him from a cell sitting quietly into a metastatic cancer cell.

“We estimate that 30 percent of all cancers are caused by this kind of chemistry,” Simons adds.  The little fires hurt genes that are nature’s own tiny fire retardants, so without their subduing effect the flames burn hotter; the fires then go after the body’s normal first responders.  So the firefighters don’t stop the burning; the paramedics don’t heal the injured victims.  The inflammation draws other cells called macrophages and granulocytes to the scene; they’re supposed to be part of the body’s cleanup crew.  “Unfortunately, in cleaning up, they actually make the flames burn hotter and further damage the area.”

What causes the fires? 

One huge cause is our diet.  Fat, charred meat, processed carbohydrates, chemicals in junk food, and sugar.  Basically, what we know as the Western diet – high in meat and bad carbs, low in fruits and vegetables.   How do we know this?  Because the men in the entire world least likely to get prostate cancer are men in rural Asia, who eat the traditional Eastern diet – low in meat, high in fruits and vegetables, with hardly any processed carbs.  No soda, lots of green tea.  No fries, lots of rice.  No burgers, lots of broccoli.  But when those men come to America, their risk of getting prostate cancer goes up.  Diet matters. 

“The rural Asian diet is anti-inflammatory,” says Simons.  “It may be that these men would eventually develop prostate cancer if they lived to be 120.  But they don’t.”  If you think about our campfire analogy, maybe cells still get singed, but they’re few and far between.  That critical momentum never develops.

“We are now learning that it’s essential for men to have a healthy diet when they’re young – say, between 14 and 30.”  But men of any age can benefit from turning down the inflammation with “fire-fighting” foods.

The opposite is also true:  Obesity and one of its consequences, diabetes, make these flames burn even higher.   (In fact, this may be one reason why rural Asian men are less likely to get prostate cancer: because of their diet, they have a lower body mass index, which means less stress on their cells.) “If you are overweight or borderline diabetic, you turn on more insulin to try to control your blood sugar,” says Simons.  Insulin secretes molecules called cytokines, which – thinking of our cowboys at the campfire – are like the chuck wagon, bringing in oxygen, new blood vessels and nutrients to feed the cancer.

“Some men have more sparks flying around, and men who are overweight are in this group.  The good news is that you can reduce your insulin level with exercise,” says Simons.  “There’s a lot of evidence that just being sedentary is a terrible setup for trouble later, if you have a slightly inflamed prostate and higher insulin level.”

The prostate is particularly vulnerable to inflammation, Simons adds, because it’s just chock full of inflammatory cells called prostaglandins, most likely nature’s way of protecting the fluid that makes up semen.  So the prostate is already a tinder box.

What else makes it worse?  A big one is genetics.  Some men are born with  their own fire-starter – genes they inherited from their father or mother.  If you are of African descent, or if you have a family history of prostate cancer or cancer in general, you are at higher risk of developing prostate cancer.  That doesn’t mean that you’re bound to get it, and it may be that with cancer-fighting diet, exercise, not smoking, and plain old good luck that you will never have prostate cancer.

Other causes of sparks:  Infection.   Cigarette smoking.  Emotional stress.  Not being circumcised: several stories have shown that circumcision has a protective effect, lowering your odds of developing prostate cancer, and of dying from it.  This ties in with what we’re still just learning about the role infection plays in changing the prostate’s microenvironment, and making it more susceptible to cancer.

            Okay, then what puts out the fires?

We’re still figuring this out.  A good diet, exercise, and other flame retardants such as Vitamin D.  Dietary supplements such as turmeric seem to help, as do broccoli and tomatoes cooked in olive oil (which brings out the lycopenes).  Meditation: new research suggests that this may help calm the tiny sparks and lower the chances of cancer catching fire.

And finally, there’s a huge question mark. What else helps?  “This area of research is woefully underfunded,” says Simons. There may be a bacterial equivalent of H.pylori– the nasty bacteria found to cause stomach ulcers.   New research suggests that probiotics – “good” bacteria that change the microflora in the gut – may prove helpful in preventing cancer.  Does this mean that there are bad bacteria that do their share of causing it?  Could this be related to the link between infection and inflammation?

We don’t know.  Stay tuned.

 

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

 

 

 

/1 Comment/by