Cancer: pare protein to spare the kidneys.

As lethal malignancies go, kidney cancer does not make the Top 10 list. Even in incidence, it ranks about 12th in the United States, below such cancers as uterine, ovarian, oral, bladder, melanoma, and pancreatic. However, over the past 25 years, cases of kidney cancer have been climbing steadily -- by about 2 percent annually This year, it's expected to strike more than 27,600 individuals in the United States and to claim some 11,300 lives.

A new study now suggests that a penchant for protein may be fueling the cancer's ascent.

Over the years, few clear-cut risk factors other than cigarette smoking and obesity have emerged for kidney cancer. However, several previous studies have suggested that eating patterns -- principally, diets high in animal fat, meat, and milk -- might be linked to the disease. Hoping to resolve the role of diet, Wong-Ho Chow of the National Cancer Institute in Bethesda, Md., and his coworkers administered a detailed questionnaire to 690 kidney cancer patients in Minnesota (or their next of kin) and to 707 demographically matched, cancerfree volunteers.

In the Aug. 3 JOURNAL OF THE NATIONAL CANCER INSTITUTE, Chow's team reports that after accounting for each subject's age, sex, smoking, weight, and average calorie intake, only diets high in protein--from all sources, including plants -- increased an individual's risk of developing kidney cancer.

The researchers divided their study population into four groups, or quartiles, on the basis of how much of any analyzed nutrient each subject consumed. Those in the highest quartile of total protein consumption faced almost twice the kidney cancer risk of those in the lowest quartile. What's more, the increase in risk with protein consumption occurred independent of calories, the researchers observe -- "particularly when caloric consumption was above the median intake."

The absence of any elevation in risk with increased consumption of fat or carbohydrates suggests that kidney cancer is not spurred simply by the number of calories in a diet.

Linda D. Youngman, a nutritional biochemist with the imperial Cancer Research Fund in Oxford, England, says the new findings don't surprise her. She has observed that kidney cancer is one of many malignancies whose incidence diminishes dramatically in rodents that she raises on very-low-protein diets.

Data from her studies suggest that such anticancer effects may trace to the ability of low-protein diets to reduce the assault on the body by biologically damaging free radicals (SN: 11/21/92, p.346). Arginine -- an amino acid building block of many proteins -- is a precursor of nitric oxide (NO), a free radical, explains cell biologist Erkki Ruoslahti of the La Jolla (Calif.) Cancer Research Foundation. So if dietary protein fosters kidney cancer via the production of free radicals, Ruoslahti says, "It's possible that arginine -- as a source of NO -- might be the constituent of protein causing this effect."

However, there are other pathways by which protein may affect kidney cancer risk, notes nephrologist Wayne A. Border of the University of Utah School of Medicine in Salt Lake City For instance, transforming growth factor beta (TGF-beta), an immune system messenger produced by the body can be a tumor promoter. And experiments that Border's lab conducted together with Ruoslahti indicate that in rats, diets low in protein suppress the kidney's production of TGF-beta.

Moreover, Ruoslahti notes, kidney disease is almost invariably associated with increased TGF-beta production. As such, he says, protein's TGF-beta connection may also explain why a history of certain kidney diseases increases an individual's risk of developing kidney cancer.