Kidney Cancer May Be Due to Lipid Peroxidation

Lipid peroxidation, which is increased in obese and hypertensive subjects, may be partially responsible for the increased risk of renal cell carcinoma in these individuals.

Last year in the United States alone, there were about 30,800 new cases of kidney cancer, and about 12,100 people died from the disease, according to the American Cancer Society. Most kidney cancers are renal cell carcinomas. Kidney cancer cases have risen dramatically in the United States and Europe in the past three decades: by the mid-1990s, rates for both men and women were 50% higher than comparable rates in the early 1970s.

"The idea of lipid peroxidation as a mechanism for renal cell carcinoma unites many of the known risk factors for this cancer,” explains Dr. Manuela Gago-Dominguez of the University of Southern California (Los Angeles, USA) . "Obesity and high blood pressure, which are known to increase kidney cancer risk, are both associated with lipid disturbances—as are numerous other risk factors.”

As reported in the April 2002 issue of Cancer Causes & Control, researchers from the University of Southern California (Los Angeles, USA; www.usc.edu) analyzed more than two dozen published reports and found increased signs of lipid peroxidation in the blood of those who are obese, those with high blood pressure, smokers, diabetic patients, and women who had had a hysterectomy and oophorectomy. Lipid peroxidation also increased in the kidney cells of rodents after testosterone treatment or oophorectomy.

In experimental animals, lipid peroxidation of the proximal renal tubules is a necessary mechanistic pathway in renal carcinogenesis induced by several different chemicals. Some of the byproducts of lipid peroxidation have been shown to damage the DNA in kidney cells. The body tries to repair the damaged DNA, but if the repair goes awry, that can lead to mutations in genes that trigger the growth of cancerous cells or deactivate genes that suppress cancer.

"If lipid peroxidation is the fundamental mechanism behind the link between obesity and hypertension and kidney cancer,” says Dr. Gago-Dominguez, "then developing therapeutics or chemopreventive agents that can decrease lipid peroxidation at the target site--and administering such drugs to cancer patients and those at high risk for the cancer--would lessen the burden of kidney cancer morbidity and mortality.”



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