MEDICINE / AIDS RESEARCH : Study Suggests AIDS Virus Can Cause Cancer
Researchers at UC San Francisco say they have found the first evidence that the human immunodeficiency virus, which causes AIDS, also can cause cancer rather than simply make patients susceptible by weakening their immune system.
In a study involving just four AIDS patients with what may be a previously undiscovered form of lymphoma, the scientists reported that the virus had inserted itself into the DNA of malignant tumors, lodging next to a cancer-causing gene. They theorize that the virus activated this “oncogene,” spawning the malignancy. Top experts, however, are skeptical of the findings.
Although lymphoma, or cancer of the lymph system, is common among AIDS patients, previous studies have shown that the cancer is not directly caused by HIV but occurs because the virus depresses the immune system. If the San Francisco research proves correct, it would mark the first time that scientists have shown that HIV is a direct cause of cancer.
“It’s a totally different perspective of what HIV can do,” said Dr. Michael McGrath, the senior author of the study, which will appear next week in the journal Cancer Research.
If the research is confirmed, the study could have broad implications for the treatment of AIDS patients and also the development of an AIDS vaccine. The findings suggest that even if effective treatments for AIDS are developed, those who have HIV could still develop cancer years after being infected with the virus.
“If it’s correct, I think its very important,” said Dr. Irvin Chen, director of the UCLA AIDS Institute. “But I’m a little skeptical of the data.”
The type of lymphoma tumors McGrath and his colleagues studied have never before been identified and contain different properties than those typically found in AIDS patients. Dr. Alexandra Levine, an expert in AIDS-related cancers at USC, said it is possible that what the San Francisco team believes is lymphoma is not a malignancy but simply an abnormal reaction to HIV.
“I don’t believe they have proven in any sense that they have found a new kind of cancer,” Levine said. “It’s a scientific curiosity that warrants further study, but they are not discussing classic AIDS lymphoma.”
In nearly all AIDS patients who have lymphoma, the malignant tumors are “monoclonal”--meaning they are derived from one type of cell, almost always a B-cell, an immune system cell that makes antibodies. A small number of cases--between 35 and 50--have been identified in which the cancer derives from other immune system cells, called T-cells.
But at San Francisco General Hospital, McGrath said, doctors have been seeing an increasing number of lymphomas that are “polyclonal”--derived from a collection of B-cells, T-cells and also macrophages, a third type of immune system cells.
Over the past decade, McGrath said, he has seen 280 patients with this unusual form of lymphoma. Today, he said, nearly a third of all the hospital’s patients with AIDS-related lymphoma have strains that are not derived from B-cells.
His team tested tissue from 30 such patients. In four, they reported finding evidence that HIV had integrated itself into the genetic material of the tissue, always in the same spot, next to the cancer-causing gene. Since that time, McGrath said, he has identified three more patients who fit this profile.
How frequently this occurs remains unclear. But the study suggests it takes years for this type of lymphoma to develop. As the AIDS epidemic moves into its second decade and HIV-infected people continue to live longer, more cases are likely to emerge, McGrath said.
If the findings are confirmed, they could prove detrimental to efforts to develop an AIDS vaccine, according to Dr. William Blattner, chief of viral epidemiology at the National Cancer Institute.
With several vaccine candidates failing to live up to their initial promise, Blattner noted that the best prospects may lie with a “live attenuated vaccine,” formulated with a live, although weakened, form of the AIDS virus. But many scientists fear that a live virus vaccine would be too dangerous, and the San Francisco study may enhance those fears.
In other AIDS research, the final results of the controversial Concorde study were published Thursday and confirmed preliminary findings reported a year ago: The drug AZT does not delay the onset of AIDS when given to patients who are infected with HIV but have not yet shown any symptoms.
AZT has been shown effective in prolonging the life of patients with full-blown AIDS, and previous studies have suggested it was beneficial to give the drug to patients before they showed symptoms. The Concorde study has cast doubt on the earlier research and generated great debate among doctors about when to prescribe AZT.
