Meat on the grill is as much a part of the Fourth of July as fireworks and American flags. But it is also reputed to increase cancer risk in unsuspecting patriots, thanks in part to chemical compounds formed when meats containing muscle — including beef, pork, poultry and fish — are cooked at very high temperatures.

The class of chemicals known as heterocyclic amines, or HCAs for short, were first discovered in the 1970s by Japanese scientists, who noted that compounds in the charred parts of cooked fish and meat were capable of damaging cellular and bacterial DNA in test tube experiments.

In studies conducted in the 1980s and 1990s, the compounds — more than 10 different HCAs have been identified so far — caused tumors in mice, rats and monkeys.

The news that charred meats contained potentially cancer-causing compounds piqued scientists' interest: It offered one explanation of a link researchers had found between meat consumption and an increased risk of certain types of cancer, said Geoffrey Kabat, a cancer epidemiologist at Albert Einstein College of Medicine in New York.

In the last decade, a handful of studies in humans populations began to suggest that HCAs might be behind the observed association between meat consumption and cancers of thepancreasprostate and colon.

For example:

Two studies led by Kristin Anderson, an epidemiologist at theUniversity of Minnesota, compared the meat consumption of people with pancreatic cancer with that of healthy people, and found that the risk of pancreatic cancer was more than doubled in people who ate the most barbecued and fried meats (particularly red meats) compared with those who ate the least. The studies were published in 2002 and 2005.

"We can't say for certain that [HCAs] are bad actors, but the evidence looks very strong that they may be," Anderson said.

A 2005 report by researchers at the National Cancer Institute looked at the relationship between meat consumption andprostate cancer in the more than 29,000 men enrolled in the national Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. They found that men who consumed more than 10 grams (about one-third of an ounce) per day of very well-done meats, including steak, bacon, sausage, pork chop and hamburger, had a 40% higher risk of prostate cancer compared with people who never ate well-done meat.

And a 2009 study of more than 175,000 adult men who were followed for nine years found that consuming barbecued and grilled red or processed meats was linked to a roughly 10% increase in the risk of prostate cancer.

In 2007, a report by the World Cancer Research Fund and American Institute for Cancer Research concluded there that was not enough evidence to link HCAs to an increased risk of the disease. But last year, researchers at the National Cancer Institute found (from a study tracking more than 2,000 people for more than 7 years) that those who consumed the most of two HCAs found in well-done barbecued hamburgers — MeIQx and DiMeIQx — had a roughly 20% higher risk ofcolon cancer compared with those who consumed the least.

But all of these studies are observational, which means that they can't yet prove a link between charred meat consumption and cancer. "There is no smoking gun," Kabat said.

"It's not like evidence for smoking and lung cancer, or evenestrogen therapy and endometrial cancer," where large, long-term studies consistently showed a very strong link between exposure and disease, Kabat said.

The HCA theory is just one of several that could explain the association between meat consumption and elevated cancer risk, said Marji McCullough, a nutritional epidemiologist with the American Cancer Society in Atlanta.

Nitrites, found in processed meats, are known carcinogens. Heme iron (also called free iron), found in meat, produces free radicals that may damage cells and trigger cancer. Meats cooked at high temperatures also contain compounds called polycyclic aromatic hydrocarbons, or PAHs, which are known carcinogens.

As scientists try to sort this out, there are a number of ways to reduce the HCA content of cooked meat.

For example, Anderson said, reducing time on the grill and temperature can cut down on HCA formation. She also recommends wrapping meat in foil before barbecuing it, keeping it away from direct flames, and cooking it for the minimum time necessary.

Studies have shown that microwaving meat for a few minutes prior to barbecuing can cut down on the number of HCAs produced by as much as 90%. Marinating also reduces HCA formation, although scientists are not sure why, McCullough said.

McCullough offered another piece of advice: cutting back on meat by grilling tofu, vegetables or kebabs made with small pieces of meat combined with vegetables.

She added that there are several well-established ways to prevent cancer, including quitting smoking, getting screened for colon cancer and adopting a healthy diet. These, she said, will do far more for people's health than getting overly concerned about a barbecue meal on one special day of the year.

health@latimes.com