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Studying the obesity-cancer link

Although not truly understood, the association between obesity and cancer risk presents some intriguing ideas.

March 07, 2011|By Karen Ravn, Special to the Los Angeles Times

Scientists might be able to come up with useful interventions if they knew exactly how body weight influences cancer risk — but they don't.

They have some promising ideas, though.

Obesity has long been associated with a higher risk of postmenopausal breast cancer, and recent studies suggest that this link may be traced, at least in part, to extra estrogen and other hormones.

Estrogen levels after menopause can be up to twice as high in obese women as in lean women. That's because before menopause, most of a woman's estrogen is made in her ovaries. But after menopause, the ovaries retire from active duty, and fat tissue takes over the estrogen-manufacturing chores.

Not all fat is created equal, though. "Abdominal fat is the active fat, the fat that produces hormones," says Donna Spruijt-Metz, associate professor of preventive medicine at USC. In other words, it may be safer for women to be pear-shaped than apple-shaped.

Chronic inflammation may provide another link between obesity and cancer, Spruijt-Metz says. "When you're fat, it's like running a low-grade infection all the time."

Michael Karin, a professor of pharmacology and pathology at UC San Diego, has studied the effects of inflammation on liver cancer in mice. He first showed that obesity causes mice to develop liver tumors. Next he traced the cause to two inflammatory compounds, interleukin 6 and tumor necrosis factor.

Mice treated with the same anti-inflammatory drugs that people use to treat rheumatoid arthritis and Crohn's disease accumulated less fat in their livers — a positive sign. "To get liver cancer, you need to get a fatty liver," Karin says.

Metformin is another drug that many believe could be useful in lowering cancer rates. It was only by chance that scientists discovered that the popular diabetes treatment simultaneously curbed cancer risk in patients. In its first human trial as a cancer preventive for non-diabetics, reported last fall, it led to a significant decrease in a particular marker for colorectal cancer.

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