Inflammation is known to be the culprit in many cancers – and perhaps prostate cancer is one of them.
When researchers look at prostate cancer specimens through a microscope head, they often see a mess: cancer cells visible under the microscope – that’s for sure – and some abnormal precancerous cells. On top of that, there is a third type of cell: a crumpled, withered cell that looks weak, but actually divides rapidly. These sickly cells are always surrounded by some chronic inflammation.
This is no accident. Inflammation is always common in patients with prostatitis and even prostate cancer. De Marzo, an oncologist at Johns Hopkins School of Medicine, speculates that inflammation is likely to be both a symptom and a cause of the disease. There is a growing body of research scholars who support this view. If that’s the case, perhaps someday doctors will treat or even prevent prostate cancer by lowering the body’s immune response.
Inflammation is a double-edged sword
Inflammation, thin and fickle. It protects us from pathogens and kills cells that are suspected of being cancerous; yet, in attacking potential pathogens, it often leads to damage to the body. “Inflammation is a double-edged sword.” De Marzo says.
In the past 20 years, scientists have begun to clarify how inflammation leads to tumors. Stomach, liver, bladder and colon cancers have all been strongly linked to inflammation.
Animal and human trials have also shown that prostate cancer is likely to be linked to inflammation in the same way they are. “It’s still hard for us to be sure that inflammation is the culprit in prostate cancer,” De Marzo said, “but we’re uncovering evidence.”
One reason it’s hard to be sure is that the specimens currently available for prostate cancer studies are all from isolated prostate specimens taken from biopsies of patients with elevated PSA, which is produced by prostate cancer and at elevated concentrations suggests a risk of developing prostate cancer. However, simple chronic inflammation can also cause an elevated PSA, so it is likely that the patient is having a biopsy for prostatitis and is more likely to detect a small, easily missed tumor. If this is true, then the speculation about the link between inflammation and prostate cancer is really just that: speculation.
De Marzo, Lucia, and colleagues have found a way to avoid this “confirmation bias. They used data from the Prostate Cancer Prevention Trial from 1993 to 2004, in which participants who did not undergo a biopsy were asked to undergo one, even if their PSA levels were too low.
The trial took benign tissue from 400 patients treated with placebo, half of whom had been diagnosed with prostate cancer. de Marzo found that inflammation was fairly common among these patients, accounting for 78 percent. However, inflammation was much more common in patients with prostate cancer, accounting for 86 percent. Inflammation then accounted for 88 percent of patients with the more aggressive, high-risk prostate cancer.
”This would suggest that there is indeed a link between prostate cancer and inflammation,” Lucia said, “and that as inflammation levels increase, so does the risk of having prostate cancer, especially high-risk prostate cancer.”
While De Marzo and Lucia’s study adequately demonstrates the link between inflammation and prostate cancer, it does not prove a causal relationship between them – exactly who came first and who came second. “We just saw a lot of inflammation in the experimental samples, but we couldn’t know which was the cause and which was the symptom.” Lucia added, “We also can’t be sure: if removing inflammation reduces prostate cancer risk.”
Inflammation and diet
If inflammation does lead to prostate cancer, what causes it? For a long time, infection was the number one suspect.
In the 1950s, researchers found that men who had not been circumcised had a higher risk of prostate cancer. This finding led researchers to believe that prostate cancer is caused by a sexually transmitted pathogen that is likely to be more common in uncircumcised men. This hypothesis is supported by population-based studies. Gonorrhea, Chlamydia and Trichomonas infections increase the risk of developing prostate cancer.
Today, such infections can be quickly cured with antibiotics, but rodent models suggest that short-term infections can lead to long-term or chronic inflammatory responses. Karen Sfanos, an oncologist at Johns Hopkins School of Medicine, found that inflammation stays in the gland for a lifetime after the bacteria are clear in the prostate of rats and mice. “Even word infections can cause a chronic inflammatory response,” Sfanos said.
To add to the headache, sexually transmitted pathogens may not be the only pathogens that can enter the prostate, thanks to the location of the prostate in the body. “The urethra passes through the prostate,” Sfanos says, “so the prostate is likely to be continuously exposed to a large group of microbes.”
Sfannos has found that E. coli, which can cause urinary tract infections, can also cause an inflammatory response in the rodent prostate; so can Propionibacterium acnes, which can cause acne. This also led the researchers to find that men with a history of severe acne had a higher risk of dying from prostate cancer.
While infections are likely to cause these chronic inflammatory conditions, scientists haven’t spared another big suspect – lost food at the dinner table. Prostate cancer is more common in the United States and Western Europe and less common in Asia. “Diet is likely to be a factor in this difference.” Elizabeth Platz of the Johns Hopkins University School of Public Health said.
Studies show that consuming specific foods can increase or decrease the risk of developing prostate cancer. For example, a diet rich in red meat, especially burnt meat, appears to increase the risk of the disease. Rats fed PhIP (a carcinogenic substance commonly found in meat foods) developed cancer in the lateral lobe of the prostate. Notably, the cancerous prostate lobes were accompanied by a large collection of inflammatory cells. Foods with anti-inflammatory effects, such as soy and green tea, have been shown to reduce the incidence of prostate cancer in animal studies. Epidemiological studies have also found that these foods do reduce the incidence of prostate cancer in the population.
De Marzo believes that the chronic inflammation of prostate cancer may result from a combination of many factors, “some of which specifically target the prostate,” he says, “and we suspect that infectious and dietary factors are what act specifically on the prostate in combination with each other and cause cancer. “
Release of carcinogens
In his studies of prostate inflammation, De Marzo has noticed those strange crumpled cells that he calls Proliferative Inflammatory Atrophy (PIA). Although the PIA surface looks crumpled, it divides as fast as cancer cells. Sometimes, PIA cells seem to combine with abnormal benign prostatic intraepithelial neoplasia (PIN) cells, which have always been seen as precancerous lesions. And, there is often some chronic inflammation around it that seems to be responsible for the damage.
Inflammatory cells produce some oxidants that damage DNA and also secrete transduction factors that signal proteins that regulate the proliferation of surrounding cells.
There is a growth differentiation factor 15 (GDF-15) that regulates inflammation. GDF-15 is common in healthy prostates, but rare in prostate specimens with chronic inflammation, so it may play a decisive role in the regulation of inflammation and produce some protection of the prostate.
If it can be confirmed that infection is one of the causes of prostate cancer, then the study of inflammation would be significant for the prevention of prostate cancer. If the hypothesis is true, it may be possible to cure or prevent many prostate diseases in the future by treating inflammation.