PCBs linked to rise in lymph cancers.

The incidence of non-Hodgkin's lymphomas--a family of cancers that attack the body's infection-fighting lymph system--has mushroomed since World War II. Because the dramatic rise has occurred globally, even in areas with traditionally very low rates of the disease, epidemiologists have been examining whether exposure to one or more environmental agents might be propelling the cancer's climb.

A new study has found provocative evidence that polychlorinated biphenyls (PCBs)--banned but still ubiquitous oils used to insulate electric transformers and other equipment beginning in the late 1930s--may be one such agent.

Several studies of agricultural workers had suggested a link between DDT and lymphomas, so Nathaniel Rothman of the National Cancer Institute in Bethesda, Md., and his coworkers decided to investigate this possibility. They tapped into the Campaign Against Cancer and Stroke study, sponsored by Johns Hopkins University in Baltimore, Md., which had enrolled nearly 26,000 healthy participants in 1974.

Over the years, 74 of the volunteers had developed non-Hodgkin's lymphoma. Rothman's team identified two healthy study participants matching the age and sex of each cancer patient and then measured DDT and other organochlorines in samples of blood serum that had been collected from these individuals some 20 years earlier.

To our surprise, Rothman says, "we saw no DDT link." Instead, they observed an unexpected correlation between PCBs and the disease. In the July 26 LANCET, his team reports that people with PCB concentrations of more than 1,050 parts per billion (ppb) in their blood's fat globules have a 4.5 times greater risk of this cancer than people with 250 to 650 ppb.

"The size of this effect is bigger than what we see in a lot of epidemiology studies," Rothman says, but it needs to be confirmed--with more patients.

Oncologist Lennart Hardell of the Orebro (Sweden) Medical Center Hospital offers support for the link, though in a far smaller population. Last year, his team reported data from 28 people with the lymphoma and 17 healthy individuals. Compared to the healthy people, the cancer patients tended to have higher PCB concentrations in body fat but equivalent amounts of DDT.

Does such a link make sense biologically? "I think most people would say yes," argues NCI epidemiologist Patricia Hartge. Several studies have indicated that PCBs can suppress the immune system, she notes. Moreover, a number of small studies by Hardell and others have turned up hints that other organochlorines might pose a non-Hodgkin's risk.

Finally, she observes that although AIDS, organ transplantation, and certain rare genetic disorders appear to predispose individuals to developing non-Hodgkin's lymphomas, these risk factors "couldn't begin to explain the level of increased incidence that has occurred throughout the world." For instance, in white U.S. men, the annual rate rose from 6.9 cases per 100,000 before 1950 to 17 per 100,000 by 1988.

The new U.S. study also hints that active infection with the Epstein-Barr virus greatly exacerbates the cancer risk of PCBs. "It's a hypothesis I suggested several years ago," Hardell notes, and one he plans to probe further in non-Hodgkin's lymphoma patients.

Some researchers worry that the PCB link indicates the cancer may also be associated with dioxins--ubiquitous chemicals structurally similar to PCBs. Some PCBs resemble dioxins in their effects on health, but Rothman's new study did not measure conventional dioxins, notes Linda S. Birnbaum of the Environmental Protection Agency in Research Triangle Park, N.C. So it's unclear whether the link between PCBs and non-Hodgkin's lymphoma traces to activation of the cell receptor where dioxins attach. To understand how PCBs work, she notes, "you'd like to be able to rule that out."