The incidence of non-Hodgkin lymphoma (NHL), a cancer involving white blood cells of the immune system, has steadily risen, nearly doubling over the past 30 years. Some of the change is related to AIDS, which substantially increases the risk of NHL, and some may have resulted from better diagnosis, but the reasons for the long-term rise are largely unknown. Some researchers speculate that the increase is due in part to exposure to environmental agents.
Epidemiologic evidence points to one possible culprita class of chemicals called organochlorines, which include certain pesticides, polychlorinated biphenols (PCBs), and dioxins. Many have been manufactured in large scale since the 1930s, and their chemical properties make them resistant to degradation by water, sun, and microorganisms. So, even though most were banned or their use restricted in the l970s and l980s in developed countries, they are persistent pollutants in the air, water, and soil, and they accumulate in the fatty tissue of animals and humans. The most widespread organochlorines in the environment and human tissues are PCBs, DDT, and DDE, a breakdown product of DDT.
According to the Agency for Toxic Substances and Disease Registry, "most of the human studies involving PCBs have many shortcomings, which make it difficult for scientists to establish a clear association between PCB exposure levels and health effects." However, from the evidence of liver cancer in animals, the National Toxicology Program's Report on Carcinogens lists PCBs as "reasonably anticipated to be a human carcinogen." The Environmental Protection Agency has set standards for PCBs in drinking water, and the U.S. Food and Drug Administration has set limits for PCBs in various foods. Besides cancer, human studies have found associations between PCB exposure and adverse developmental and reproductive effects as well as nervous system damage.
PCBs were produced in the United States from 1929 until 1977. Initially, PCBs were used as coolants and lubricants in electrical equipment, such as transformers and capacitors, but after 1957 they were used primarily in hydraulic fluids, flame retardants, paints, plasticizers, pesticides, and wood preservatives. Production stopped because of accumulating evidence that exposure to PCBs is associated with adverse health effects, including cancer. Today, PCBs can still be released into the environment from poorly maintained hazardous waste sites, dumping of wastes (e.g., old transformer fluid, fluorescent lighting fixtures, appliances, or televisions), or burning of waste in municipal and industrial incinerators.
"Although PCBs and DDT were banned in the United States in the 1970s, exposure to these compounds was once widespread, and they continue to be ubiquitous environmental pollutants," said Joanne Colt, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute.
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The researchers compared the agents found in the carpet dust in the homes of 603 patients with NHL to those found in the carpets of 443 control subjects. A 50% increased risk of NHL was associated with exposure to any of five types of PCBs commonly found in environmental samplesPCB 105, 138, 153, 170, or 180. However, a statistically significant dose response was seen only at increasing levels of PCB 180, with a 70% increased risk of NHL at the highest exposure levels. A dose response was also seen with DDE, with a 60% elevation in risk at the highest levels.
"If the association observed in our study is real, these compounds could have contributed to the risk of NHL observed over the past several decades," Colt said. "Although contaminated carpet dust is not a major route of exposure to these compounds for adults, their presence in carpet dust today could be indicative of exposures that occurred many years ago."
A dozen or so previous studies of NHL and specific organochlorine exposure in the general population have had similar results. Colt's study was the first to look at NHL risk and organochlorine levels in carpet dust. She and her colleagues expect to publish data on levels of organochlorines in blood samples from the same case patients and control subjects later this year.
"Although diet is assumed to be a major contributor to organochlorine exposures, this finding indicates that nondietary exposures could be importanta very interesting finding, if true," said Penelope J.E. Quintana, Ph.D., of the Graduate School of Public Health at San Diego State University in San Diego.
Pesticides
Pesticide exposure and NHL risk is perhaps the most well-studied association of the organochlorines. Organochlorine pesticidesDDT, chlordane, aldrin, dieldrin, endrin, dacthal, heptachlor, lindane, methoxychlor, and pentachlorphenolwere introduced to the United States in the 1940s and, like PCBs, persist in the environment long after they are applied. The EPA banned or restricted the use of many of them during the 1970s and 1980sDDT was banned in 1972, endrin in 1986, dieldrin and aldrin in 1987, and chlordane in 1988. People can be exposed to organochlorine pesticides by eating fatty foods, such as milk, dairy products, or fish that are contaminated with these pesticides; by eating food imported from countries that still allow the use of persistent pesticides; or by absorbing these pesticides through the skin.
In studies in farmers, NHL has been associated with three different chemical classes of pesticides, including organochlorine pesticides. However, it is not clear which particular pesticide may be responsible for the elevated risk or whether other farm exposures such as dust, solvents, fuels, animal viruses, and fertilizers may play a role. The organochlorine pesticides chlordane, dieldrin, and lindane have been associated with NHL in past studies, but not consistently.
Despite this uncertainty, many pesticidesincluding organochlorinesare classified as possible or probable carcinogens because of evidence in animal studies. But many countries in Asia, Africa, and South and Central America continue to use organochlorine pesticides for crops and malaria control. In Mexico, where DDT is still used, high concentrations of DDT in human breast milk have been reported.
PBDE
Not all persistent chemicals are regulated by governments. A synthetic flame retardant, polybrominated diphenyl ether (PBDE) has come into common use in the United States during the last three decades and is accumulating in human blood, milk, and food. PBDEs are currently widely used in consumer products, such as plastic foam, computers, televisions, fabrics, and carpet linings.
"U.S. human tissue levels of PBDEs have increased markedly during the past several decades, which reflects the increased use of PBDEs beginning in the 1970s," said Arnold Schecter, M.D., from the University of Texas School of Public Health in Dallas.
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The Larger Picture
Looking at the larger picture, there is good news on two fronts. The incidence of NHL in several countries has been leveling off. Data from the Surveillance, Epidemiology, and End Results (SEER) program at NCI show that during 19751990, the annual percent change in NHL was +3.6% compared with +1.6% during 19901995 and 0.9% during 19952000. Similar trends in NHL rates are seen in Sweden, Denmark, and Finland, where many organochlorines are also banned.
Also, studies from Sweden, Germany, the Netherlands, Japan, Canada, and the United States have reported decreasing levels of some organochlorines in human tissue and the environment. A survey of worldwide trends in DDT levels in human breast milk from several continents over five decades showed that these concentrations have declined in most areas of the world, consistent with restrictions on its use. In the United States, the Agency for Toxic Substances and Disease Registry reported that between 1978 and 1991, the estimated daily intake of PCBs in adults from dietary sources declined from about 1.9 ng to less than 0.9 ng.
Along the same lines, Schecter and his colleagues reported in the March issue of the Journal of Occupational and Environmental Medicine that the serum levels in 2003 of certain organochlorinesPCBs, dioxins, and dibenzofuranswere substantially lower than samples from 1973.
Whether there is a relationship between the changing NHL rates and the levels of chemicals is not certain, but the hypothesis seems reasonable to many scientists. One of those is Lennart Hardell, M.D., Ph.D., from the Department of Oncology at University Hospital in Orebro, Sweden, who wrote a recent article in Environmental Health Perspectives on the declining rates of NHL. He said that the leveling off of the incidence curve of NHL could be explained by the decreasing exposure to one or several environmental agents, and may be a "good example of how prohibition and limitation of exposure may be reflected in cancer statistics some years later."
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