In This Section      
 

Exploring the Link Between Evolution and Prostate Cancer

Exploring the Link Between Evolution and Prostate Cancer

Updated: 12/22/2015

Scientist Don Coffey, Ph.D., has taken a four-million-year detour in his search to explain prostate cancer and learned that in the very big scheme of things, it’s an illness of fairly recent evolution. Like heart disease, it is an apparent casualty of the sedentary Western lifestyle and its notoriously unhealthy diet rich in animal fat, processed fare, fast food and other junk. In other words, it's the dark side of progress.

As remarkably adaptable as the human body is, there are some forces that nature never equipped humans to handle. How ironic that the same people who have learned to defy gravity can be brought down by years of supersized bacon burgers and meat lover's pizzas. Today's man is far more likely to spend hours hunting for websites or TV channels than foraging for food. His fingertips are more likely to be stained by Cheetos than by the juices of berries.

According to Dr. Coffey, humans did not evolve and develop to eat this way. Dr. Coffey and his colleagues Angelo De Marzo, M.D., Ph.D., and William G. Nelson, M.D., Ph.D., are discovering on a microscopic level how this drama of evolution plays out in the most primitive, fundamental cells in the prostate. This groundbreaking research may one day lead to the earliest marker yet for prostate cancer and may help scientists prevent or even reverse cell damage before it's too late.

An Evolutionary Wrong Turn

The saga of human evolution is also a story of two male glands, both of which produce fluid that makes up semen. One gland, the prostate, is prone to cancer. The other, the seminal vesicle, is remarkably free of it.

Only mammals have prostates. By definition, only mammals have breasts, as well. Breasts and prostates seem to have evolved on parallel tracks. The prostate first appeared in males when females developed breasts and fed their children with breast milk. Today, breast cancer and prostate cancer seem to be two sides of the same coin. Countries with high rates of breast cancer tend to have high rates of prostate cancer. And countries with low rates of prostate cancer have relatively few cases of breast cancer. When people migrate from areas with low rates of breast or prostate cancer to places with high rates, their own odds increase with time.

In nature, animals that are meat-eating carnivores don’t have seminal vesicles. The only animals that have both prostates and seminal vesicles are herbivores — vegetable-eating animals, such as bulls, apes and elephants.

Humans are the exception to this rule since men have seminal vesicles too. In other words, man, a meat-lover, has the makeup of an animal that should be a vegetarian. The fact that humans eat meat seems to be a mistake that nature never accounted for. In exploring this phenomenon, Dr. Coffey looked a few rungs further down the evolutionary ladder and found the pigmy chimp called the bonobo. Bonobos and humans have many things in common. Diet is not one of them. Bonobos are vegetarians. And they don't get prostate cancer.

Most apes only eat fruits and vegetables and greens. After climbing down out of the trees, humans became hunter-gatherers. It wasn’t until recently that humans started eating and processing meat in a big way.

Major Change in Diet and Lifestyle

About 12,000 years ago, humans took the next big step and started producing their own food. They changed from the way they had evolved and started eating more processed meat. Instead of running after animals, they started herding them and then breeding them in captivity. This led to a sedentary lifestyle.

At this point, they reduced their intake of fresh vegetables and greens from 3,000 types down to about 20. They started smoking and salting meat, Now we get everything from the store, nothing from a farm. We call it fresh, but it's not fresh — especially not our meat.

For decades, the American Cancer Society and National Cancer Institute have urged Americans to lower their cancer risk by changing their diet. These organizations encourage people to reduce animal fats and dairy products. Humans weren’t eating dairy until 3,000 years ago. Now we put cheese on everything. A few apes eat meat, but no ape ever cooked or put cheese on anything. Humans need more fiber and more fresh fruits and vegetables in their diet. And they need more aerobic exercise. Cancer prevention research shows that humans should return to the way they evolved.

Dr. Coffey reviewed zoo records from around the world and found that no aging animals in the zoo die from prostate cancer or breast cancer. There are only three cases of cats dying of prostate cancer. Only a few primates have ever died of it. Yet one out of every 10 American men gets prostate cancer. And the only animal to develop clinical prostate cancer with any significant incidence is the dog, the pet that eats the most leftovers from their human masters.

New Finding Exposes the Roots of Cancer In the Prostate

To understand how diet causes changes that lead to cancer, Dr. Coffey and his colleagues John Isaacs, Ph.D., Angelo De Marzo, M.D., Ph.D., Alan Meeker, M.A.T., Ph.D., and Bill Nelson, M.D., Ph.D., have combined their efforts to implicate what appears to be a tiny garden of good and evil, tucked away deep in the prostate. This hidden nursery of thousands of stem cell seeds divide and grow into mature prostate cells that accumulate.

These stem cells can make your prostate grow or shrink. Taking away androgens (male hormones that feed and stimulate the prostate) causes the mature cells to shrink. Giving the androgens back causes those seeds of stem cells to grow back. Normally, these stem cells divide and then don't divide; they turn on and off like a light bulb. When they divide, they give birth to tall stalks called mature epithelial cells. These epithelial cells, in turn, become little factories that produce PSA and the fluids that make up the prostate's contribution to semen.

When all is well within the prostate, these fragile stem cells are cherished, sheltered and safeguarded. They are cushioned by protective enzymes like glutathione S-transferase Pi 1 (GSTP1) that safeguard them from anything that might damage their DNA. At the very earliest stages of prostate cancer, some of the important properties possessed only by the stem cells, such as the ability to divide and grow indefinitely, shift up into the mature epithelial cells. Ordinarily, this would be fine because the epithelial cells can turn on their GSTP1 and stay protected.

But Dr. Nelson discovered that sometimes, in patients who develop cancer, a destructive force obliterates the GSTP1. Without their enzyme bodyguard, the dividing epithelial cells are suddenly vulnerable. Once they've lost their ability to protect themselves, they start accumulating DNA damage. The epithelial cells start replicating like crazy, churning out several different species of damaged cells, many of which are cancerous.

Because there’s such a significant variation, these cells are highly resistant to therapy. The errant process creates biological diversity in the prostate at the wrong time, turning on evolution at the wrong time. If something goes wrong in the stem cells and they start to go out of control, they don't have this unprotected replication. When they build up, they just make more normal cells. This results in the enlargement of the prostate, which is a condition known as benign prostatic hyperplasia (BPH). It does not lead to cancer.

According to Dr. Coffey and Dr. De Marzo, this may be the equation, or at least a part of it, for prostate cancer:

Absence of GSTP1 + wild replication in the epithelial cells = cancer

As long as replication happens in the stem cells, where the protective mechanisms exist, the cells are fine. But in prostate cancer, these stem cells disappear, and it's the epithelial cells that are dividing and that’s what kills patients.

This revolutionary research has resulted in a new way of explaining how prostate cancer and BPH develop and how they're different.

The Role of Free Radicals

So what allows the DNA-damaging forces in the prostate? The researchers believe that the answer may be found in the diet. Dr. De Marzo and Dr. Coffey have discovered a subtle change in prostate tissue, a small-scale inflammation that’s much different from the overall inflammation that characterizes clinical prostatitis. For some reason, there's a little autoimmune reaction. And this prostate inflammation makes free radicals, which attack the DNA.

GSTP1 protects against these free radicals. Soy also helps fight free radicals. Using an experiment with rats, Dr. Coffey found that when they were given a soy-free diet, they had lots of prostate inflammation. When they were fed a moderate soy diet, they got very little. When they ate a high-soy diet, they had no inflammation. The researchers discovered that diet can control inflammation and influence the behavior of enzymes in the body.

Investigation of Early Area of Cell Damage

Dr. De Marzo recently identified a new lesion in the prostate called proliferative inflammatory atrophy (PIA). It indicates a very early area of cell damage. This precedes prostatic intraepithelial neoplasia (PIN), which describes abnormal cells that are usually found in a needle biopsy and are strongly linked to prostate cancer.

While investigating PIA, scientists have noticed that the PIA cells appear to be shut down, or atrophied, and are surrounded by inflammation. In addition, they're highly active for DNA synthesis, so they’re replicating wildly.

In this volatile area, Dr. Nelson and Dr. De Marzo have observed that levels of GSTP1 fluctuate heavily. It appears that scientists are witnessing a microscopic battle, or the enzyme's last stand, which helps initiate the cancer process. PIA might also become an extremely early warning sign of prostate cancer. If PIA is reversible, it could lead to cancer being caught in its earliest stages.

 

Request an Appointment

Maryland Patients

Adult Urology: 410-955-6100
Pediatric Urology: 410-955-6108

 

Traveling for Care?

Whether you're crossing the country or the globe, we make it easy to access world-class care at Johns Hopkins.

Outside of Maryland (toll free)
410-464-6713

Request an Appointment
Medical Concierge Services

International Patients
+1-410-502-7683

Request an Appointment
Medical Concierge Services

 
blue suitcase