High iron stores may increase cancer risk.

Radiation, genes, some chemicals: All are known to cause cancer. But who'd suspect the iron in a bowl of fortified cereal?

Epidemiologist Richard 6. Stevens might. The greater the iron concentration in a person's blood, the greater the risk of developing cancer, says Stevens of the Pacific Northwest Laboratory in Richmond, Wash. He and his coworkers came to that conclusion after studying more than 8,000 participants in the 1971 National Health and Nutrition Education Survey.

"Although we aren't testing for specific cancers," Stevens says, "those of the esophagus and bladder appear most strongly linked with body iron." The link between excess iron and cancer held true even when the researchers controlled for factors known to increase the risk of cancer, such as age and smoking.

Cancer cells may need more iron to grow and replicate than normal cells, Stevens speculates. Or iron may boost the production of biologically damaging free radicals, which snatch electrons belonging to other molecules.

Iron binds with DNA in the cell's nucleus, says Lawrence A. Loeb of the University of Washington in Seattle. "If that [DNA-iron] complex is exposed to hydrogen peroxide, which we know is in cells, free radicals could be produced close enough to damage the DNA," he says.

Iron-generated free radicals may also increase the risk of heart disease (SN: 9/19/92, p. 180). "The biologic rationale implicating iron and free radicals [in disease] is pretty strong," Loeb adds.

"If iron is really a carcinogen, we're facing a lot of debate," he said, noting that a Food and Drug Administration regulation prohibits manufacturers from adding known carcinogens to food.

Right now, there's no proof of ill effects from iron. On the contrary, manufacturers are encouraged to add iron to food in order to prevent iron-deficiency anemia. "Iron deficiency remains a significant problem in this country in school-age children and women of reproductive years," says hematologist James D. Cook of the University of Kansas in Kansas City.

Stevens' team indirectly measured transferrin, a protein that stores and transports iron in the blood and other parts of the body The researchers calculated transferrin saturation from two measurements: the amount of iron found in blood serum and the additional iron the blood could store.

People with more than 60 percent of their transferrin containing iron proved most likely to develop cancer, the researchers report in the February INTERNATIONAL JOURNAL OF CANCER. The normal saturation is about 30 percent.

In the same journal, Paul Knekt of the Social Insurance Institution in Helsinki and his coauthors also report that people with transferrin saturations above 60 percent appear more likely to develop cancer. Unlike Stevens, the Finnish group saw no link at 40 to 60 percent saturation.

Stevens is confident enough of his results to question the wisdom of wholesale addition of iron to food and to suggest that periodic blood donation by those who are not anemic may benefit the donor as well as society, At least one 1990 study found a significantly reduced risk of cancer in Swedish blood donors.

"There are 50 years of work that have gone into fighting iron-deficiency anemia, and we're not at odds with them," says Stevens. "But the effects of excess iron are also darned important, and [they're] being almost entirely overlooked."