New Theory May Provide Missing Link Between Overweight, Cancer

American Institute for Cancer Research
Friday, 16 November 2001

High Insulin Levels Caused by Inactivity, Excess Weight Make Cancer More Likely, Scientists Say

WASHINGTON, DC - A specific condition that occurs in the bodies of many inactive, overweight individuals may actually encourage the cancer process, according to researchers at the American Institute for Cancer Research (AICR).

The researchers say that being overweight and inactive can cause the body to release high levels of insulin and other hormones known as "growth factors." High insulin levels -- along with several other conditions collectively known as "metabolic syndrome" or "syndrome X" -- have already been linked to cardiovascular disease and other chronic diseases.

Many cancer scientists now believe this same state of affairs is one reason cancer is more common among the overweight and obese.

"Research has demonstrated that insulin and other growth factors encourage cells to divide more rapidly," said Helen Norman, Ph.D., lead author of a new AICR review of the scientific literature on obesity and cancer risk.

"Under normal circumstances, release of insulin is tightly regulated and doesn't pose much of a risk. But in many overweight, inactive people, the tissues are constantly exposed to high levels of insulin, which causes their cells to reproduce quickly and often."

When cells reproduce rapidly, Dr. Norman said, the chances increase that something could go wrong in the process, such as the kind of random mutation that can lead to cancer.

Excess Weight, Inactivity Can Cause Specific Metabolic Changes

The emerging focus on the role of insulin is based on research showing that two related conditions called insulin resistance and hyperinsulinemia may be linked to several kinds of cancer, including breast cancer and colon cancer.

In non-obese, non-diabetic individuals, the pancreas produces low levels of insulin to help metabolize certain components of the diet - glucose and carbohydrates. But studies have shown that in many individuals, the tissues of the body become less sensitive to insulin as weight increases and physical activity drops. This phenomenon is known as insulin resistance.

As their bodies become less sensitive to insulin's effects, overweight and obese individuals experience greater difficulty converting glucose into energy. The body attempts to compensate for this by producing more insulin, a condition called hyperinsulinemia, which in turn spurs cells to divide and raises cancer risk.

"It's clear that high insulin levels coincide with a host of chronic diseases, including cancer," said Gerald Reaven, M.D., Professor Emeritus of Medicine, Endocrinology and Metabolism at Stanford University. Dr. Reaven is well known for his work studying how elevated insulin levels promote coronary heart disease.

"We've just published a paper showing that insulin resistance is a good predictor of cancer risk," he said. "But the situation is complex."

Not All Overweight, Inactive Individuals Have High Insulin

It appears that whether or not a person becomes resistant to insulin is influenced by genetic factors as well as weight status and level of physical activity. Thus, not all overweight people are insulin resistant, Reaven said.

He believes that this fact is the reason it has taken scientists so long to document insulin's role in disease risk. "Genetics does play a role in all of this, which has historically made the precise impact of weight and fitness harder to gauge. But I hasten to add that it is now very clear that insulin resistance is more common among overweight people, and that's important."

Reaven and his colleagues believe it "just makes sense" for overweight, inactive individuals to start making healthy changes to their lifestyle. His research has revealed that when overweight individuals with high insulin lose weight, their insulin levels drop and stay down for as long as they keep excess weight off.

In his view, the protective benefits associated with exercise and maintaining a healthy weight are too large and important to dismiss, regardless of genetics.

"Whether you're insulin sensitive or insulin resistant, getting regular exercise and maintaining a healthy weight are two of the best things you can do to protect yourself from disease - and improve your overall quality of life in the bargain."

Exercise Gains New Prominence as Cancer Fighter

Dr. Norman of AICR agrees. In fact, her recent review of the scientific literature on obesity and cancer risk suggests that physical activity may prove to have an even greater role in cancer prevention than was previously thought.

"Regular exercise helps to prevent the buildup of fat tissue in the first place, which in turn keeps the levels of insulin and other hormones in check," she says. "There is also growing evidence that exercise releases binding proteins that 'soak up' any excess growth factors in the blood."

Physical activity also speeds the passage of dietary and environmental carcinogens from the body. Studies suggest that this reduces the risk of colon cancer in particular because these potential carcinogens spend little time in direct contact with colorectal tissues.

Interestingly, researchers say that the colorectal cancer risk associated with excess insulin seem to be more pronounced in men. This is likely because men tend to store fat around the abdomen, and abdominal fat has been shown to secrete insulin at high levels.

Insulin's Role Only One Piece of the Puzzle, Say Experts

Dr. Rowan Chlebowski, of the Harbor-UCLA Research and Education Institute, believes there will prove to be several biological reasons that people who are overweight and inactive tend to have higher cancer rates. "The role of insulin resistance in cancer risk needs to be studied further, but it certainly represents one of the most promising avenues of research to come along in a while."

Speaking at a recent AICR conference on Nutrition After Cancer, Dr. Chlebowski noted that it has only recently become easier for researchers to measure insulin resistance and other hormonal factors accurately. Studies that investigate the role of these factors in disease risk "consistently point in the same direction," he said.

"Insulin levels have already been associated with diabetes, heart disease, stroke, cognitive dysfunction, and overall mortality," he said. "It should comes as no surprise that new research is now implicating this same insulin-regulatory pathway in several kinds of cancer."

As research continues to clarify the precise nature of this association, Chelbowski noted that the public should remember that the link between diet and cancer risk is already clear and convincing. "Diets high in vegetables, fruits, whole grains and beans fight cancer and other diseases in many ways at once," he said.

Chlebowski was referring to the evidence, reviewed in the AICR report, Food, Nutrition and the Prevention of Cancer: A Global Perspective, that substances within these foods perform a host of anti-cancer activities in the body.

Dr. Norman of AICR added that diets that highlight plant foods offer a bonus - they tend to be lower in fat and calories, which makes managing weight much easier.

Summary

Research has shown that overweight, inactive individuals have higher risk for many cancers, but a clear biological explanation for exactly why this is so has been more elusive.

Now, however, one likely reason is beginning to emerge from the research. It has been shown that being overweight and inactive can cause the body to secrete higher and higher amounts of insulin and other growth factors.

Cells exposed to high levels of these substances over an extended period of time may begin to reproduce so quickly that cancer becomes more likely.

But AICR researchers stress that this potentially dangerous condition is reversible.

Regular physical activity can help reset the body's hormonal systems and regulate the secretion of insulin.

Losing weight and keeping it off also helps restore insulin levels to normal.

As research continues, scientists will likely identify additional biological reasons that excess weight and inactivity increase risk. It is already clear, however, that diet, physical activity and weight management play key roles in cancer prevention.

For more information, or to contact American Institute for Cancer Research, see their website at: www.aicr.org