Liver cancer: homing in on the risks.

Liver cancer, one of the five leading human cancers, claims some 250,000 lives annually, primarily in Asia and Africa. Most cases can be traced to infection with the hepatitis B virus or to long-term, high-level ingestion of aflatoxins, poisons produced by a mold contaminating many crops, especially corn.

Teasing out each agent's contribution has proved difficult, because in areas where liver cancer is endemic, exposure to both tends to occur by age 2. Last week, however, researchers reported a promising marker of aflatoxin exposure and how it might be used to sort out the respective carcinogenic roles -- and interaction -- of aflatoxin and hepatitis.

This biomarker also opens the prospect of more effectively screening populations to find high-risk individuals for surveillance or cancer-prevention strategies, says chemist John D. Groopman of the Johns Hopkins University School of Hygiene and Public Health in Baltimore. Indeed, he says, clinical trials are already in progress to further investigate the safety of a drug expected to limit precancerous changes in individuals eating aflatoxin-rich diets.

Groopman described the new biomarker -- an adduct, or chemically modified form of DNA -- last week at an American Institute for Cancer Research

conference in McLean, Va. Both rat and human urine can contain this characteristic adduct, whose concentrations correspond to the amount of aflatoxin consumed. Moreover, Groopman and his colleagues reported in the Jan. 15 CANCER RESEARCH, this "adduct in urine accurately reflects DNA damage at the primary [liver] site of aflatoxin-mediated damage."

Since 1986, Groopman and an international team of co-workers have been conducting a prospective study of 18,244 initially healthy, middle-aged Chinese men in Shanghai, an aflatoxin-rich region. To date, 40 liver cancers have occurred within the group. An analysis of the first 22 cases, Groopman said last week, showed that every time the DNA adduct was present in sampled urine, the risk of liver cancer "was increased two-to three-fold," compared to adduct-free men in the study of the same age who lived in the same neighborhood.

Moreover, Groopman asserts, "for the first time, we've been able to demonstrate that there is in fact an ... [apparent synergy] between hepatitis B virus and aflatoxin exposure." Preliminary data from the Shanghai trial indicate that men with urinary evidence of aflatoxin exposure and of previous hepatitis B infection proved 12 times more likely to develop liver cancer than men with signs of hepatitis B exposure only.

Groopman's team "is onto something valuable" with this adduct biomarker, says Leonard Cohen of the American Health Foundation in Valhalla, N.Y.

Adds R. Palmer Beasley, dean of the University of Texas School of Public Health in Houston, these "terrific" studies "support an important role for aflatoxin in liver cancer." Previously, he says, the toxin's role in human liver cancer was generally accepted -- based on animal data and epidemiologic studies --but "not proven."

Last week, Groopman also reported data on a cancer-prevention trial in rats fed a high-aflatoxin diet for one month. Some of the animals also received Oltipraz - a U.S. Food and Drug Administration-approved antiparasitic drug - during that period. Though these animals excreted low levels of DNA adducts, they developed no liver tumors. By contrast, 9 percent of the animals not treated with Oltipraz developed precancerous liver nodules, and 11 percent had full-blown liver cancers.

In the body, cells convert aflatoxin into a carcinogenic epoxide. Groopman says that Oltipraz appears to protect against liver cancer by increasing concentrations of certain epoxide detoxification enzymes known as glutathione S-transferases (see p. 311).

The next step "is to ask, Does this drug affect aflatoxin metabolism in people?" If it does, Groopman told SCIENCE NEWS, experimental intervention trials in highly exposed Shanghai men might get under way within five or six years.

These data suggest "there could be some hope for the people who are at high risk [of liver cancer]," Beasley says. But any such trials should focus on carriers of the hepatitis B virus in aflatoxin-rich regions, he says, because only they "would be at high enough risk [of cancer] to justify the cost or [side effects] of the drug."