Discovery
January 22, 2016

Those of us who love steaks and hot dogs on the grill were chastened a few years ago, when scientist Bill Nelson, M.D., Ph.D., the Marion I. Knott Director and Professor of Oncology and Director of the Sidney Kimmel Comprehensive Cancer Center, began investigating something called "PhIP." PhIP (a short name for a long chemical compound) is found in meats cooked at high temperatures — think of charred burgers, or fried chicken. It is a "pro-carcinogen," a chemical that turns into something that can attack and mutate DNA, and is known to cause prostate, breast, and colorectal cancer in rats.

But there's good news: It pays to eat your veggies. "When we fed rats tomatoes and broccoli along with PhIP, the animals lived longer, and showed reduced incidence and severity of prostate neoplasms (new, abnormal cell growth; particularly of PIN, prostatic intraepithelial neoplasia — funny-looking cells that are linked to prostate cancer), intestinal cancers, and skin cancers as compared to rats fed PhIP alone," says Nelson. "This provides even more evidence that eating vegetables may protect against cancer-causing agents like those in overcooked meats."

There is also a twist to the story: Food safety pays off, as well. Nelson, along with pathologist Angelo De Marzo, M.D., Ph.D., and scientist Karen Sfanos, Ph.D. has also explored the idea that prostate cancer may involve a combination of "environmental insults" — bad things in the diet, plus something else that weakens the body, like an infection. They wondered whether chronic inflammation — caused by bacterial infection — would make a difference in rats that had consumed PhIP. Using a specific strain of E.coli, isolated from a patient with chronic prostatitis/chronic pelvic pain syndrome by urologist Anthony Schaeffer, M.D., and further studied by urologist Edward Schaeffer, M.D., Ph.D., the R. Christian B. Evensen Professor, they found, to their surprise, that the charred food plus the nasty bug (many people have E.coli in their gut and it is harmless, but some strains can get into meat when it's processed, and can survive if the meat is undercooked) seemed to have a systemic effect, causing an increase in the development and progression of cancer in the skin and digestive tract. The rats that received the double punch of E.coli plus PhIP fared worse than rats that ate the PhIP alone. In one study, the bacteria- and PhIP-consuming rats developed more precancerous lesions within the prostate and might have developed even more problems – except they also died sooner.

In further experiments, Nelson, De Marzo and Sfanos found that "when we inoculated PhIP-fed rats with E.coli in the prostate, the animals developed acute and chronic prostate inflammation out of proportion to that seen with PhIP ingestion or E.coli inoculation alone, and had more prostate neoplasms, intestinal cancers, and skin cancers. "This hints that prostate infections and dietary carcinogens might interact to promote chronic prostate inflammation and prostate cancers, and that prostate infections might augment carcinogen effects on other tissues, as well," says Nelson.

Nelson, De Marzo, Sfanos, and colleagues recently published two papers on these striking new findings in the journals PLoS ONE and Cancer Prevention Research.