Cancer Cluster: Tracking a Killer in Nevada

An environment rife with arsenic, tungsten, cobalt and jet fuel does not seem adequate to explain an unusually high incidence of childhood leukemia - three deaths and 16 cases in all - that first struck Fallon, Nevada, almost a decade ago. Despite a major public health investigation launched by the federal Centers for Disease Control and Prevention (CDC), no smoking weapon of a caliber sufficient to account for the cluster has been found. Still, driven by lingering pain and frustration, affected families in this rural town - 60 miles east of Reno on a stretch of US Highway 50 dubbed "the Loneliest Road in America" - are determined that the search continue. UCSF molecular epidemiologist Joseph Wiemels, PhD, is one of three scientists recently awarded new research grants to study the Fallon cluster. Local families had a hand in moving politicians to appropriate the money and, along with the usual scientist "peers," in deciding which research proposals to support. Not content to round up the usual toxic suspects, Wiemels will be looking for clues in past weather patterns and for viral traces in human DNA. He is even eyeing a massive radiofrequency transmitter. That may sound offbeat, but Wiemels is acknowledged as a mainstream expert on the origins of acute lymphoblastic leukemia, the type of leukemia diagnosed in all but one of the children in the Fallon cluster. With funding from the National Institutes of Health, he has investigated both prenatal and postnatal causes of the disease. Most notably, Wiemels has found associations between variant forms of enzymes that metabolize folic acid and specific leukemia-causing genetic defects in infants, and he has discovered that several leukemia-inducing mutations occur before birth. Cancer Clusters: Cause or Chance? Many epidemiologists do not like to see scarce research dollars go to investigations of individual cancer clusters. One reason is that some small populations - simply by chance - will experience more cancers than others over the same time frame. However, when residents recollect multiple cases occurring in close proximity, many often conclude that some unseen environmental exposure is responsible, even when the local environment is no worse than average.

Aerial view of Fallon and Churchill County, Nevada.

But Fallon is different. CDC scientists and many others, including Wiemels, don't think the cluster is due to chance, even though the cause of the 16 leukemia cases diagnosed between 1997 and 2002 remains uncertain. "If you look at the statistics, even using more conservative criteria for including cases, it's the most significant cluster on record," Wiemels says. "With the current population of the US, if you waited another 22,000 years, a similar cluster might happen again once by chance." Clusters of rare cancers that have occurred in distinct occupational or medical settings have sometimes been traced to exposure to chemicals, drugs or infectious disease. However, investigations of scores of residential cancer clusters by the CDC over many years have failed to turn up hard evidence for environmental causes. Sometimes this is because a cluster has arisen by chance and has no particular cause. But at other times, there may simply be insufficient information to identify exposures and link them to disease. In the world of epidemiologists, 16 cases are very few. In searching for possible disease risks, scientists are accustomed to comparing hundreds or even thousands of cases to matched controls - similar people who are unaffected by the disease. Fuel Spills Suspected An old fuel pipeline - originating in the Bay Area - runs through town on its way to Naval Air Station Fallon. Some Fallon residents doubt claims by the pipeline operator, Kinder Morgan Energy Partners LP, that there has never been evidence of leaks in the local jet fuel-carrying stretch of pipeline. Some residents also dispute assertions by the Navy that the jettisoning of fuel from overhead aircraft to simulate landings on carrier decks rarely occurred. The jet fuel, called JP-8, is kerosene-based. Like gasoline, it contains significant amounts of benzene - a known cause of leukemia - as well as lesser amounts of other volatile organic chemicals. However, government studies did not turn up any unusual levels of jet fuel chemicals in the blood, urine or water supply of leukemia patients, their families or other county residents. Metals in their Midst State and CDC research revealed that exposure to arsenic and tungsten has been much higher than the US average among the leukemia cluster patients and their families. The CDC-led investigation found evidence that this contamination is due to local geology and hydrology. Indeed, unaffected families in the county were similarly exposed. In fact, municipal and private wells had long been known to exceed Environmental Protection Agency arsenic standards for drinking water. The town finally managed to clean up its water supply in 2004. In any case, arsenic exposure is not known to increase leukemia risk, although it does increase one's risk for certain other cancers. CDC analysis of additional environmental and biological samples suggested that residents of Nevada counties outside the cancer cluster were exposed to similarly high levels of tungsten. The cancer-causing potential of tungsten has not been studied much, but the Fallon investigation has led to a call for new research on its potential health effects. The CDC concluded its investigation of environmental exposures without testing outdoor air. But in a later scientific study, a University of Arizona toxicologist, Mark Witten, PhD, reported greatly elevated tungsten and cobalt levels in airborne particulates in Fallon, compared with surrounding areas. Witten suggested it was not only local geology contributing to residents' high exposures, but also a Fallon metal plant. For a Limited Time Only? Without knowing what caused the Fallon cluster, it is difficult to assert that it will never recur. Wiemels plans to investigate phenomena that might explain why the cluster appears to be limited to a certain time frame. The long-term metal exposure on its own seems to be an unlikely explanation. "None of these things changed that dramatically immediately prior to the cluster," Wiemels says. "I think that what makes this cluster so pointed in time probably has something to do with the toxic load of the environment causing a high background rate of genetic mutation, combined with something more transient." Adding to the strange mix of real and suspected exposures in Fallon is electromagnetic radiation (EMF) from a nearby high-powered, long-range navigation (loran) radiofrequency transmitter. Residents' EMF exposure increases during wet weather, according to Wiemels. The tower, which transmits frequencies ranging from 90 to 110 kilohertz, is part of an antiquated nationwide network for determining a craft's location by triangulating signals received from distinct transmitters. Although modern GPS has largely rendered the World War II-era technology obsolete, the tower remains in place and operational. "When it rains, the whole basin where Fallon is located becomes an antenna," Wiemels says. A drought earlier in the 1990s ended with wetter years, including a very rainy 1997, during which the basin was soggy all winter, Wiemels has learned. Some studies of leukemia and EMF have found an association, while others have not. Wiemels plans to review water table and weather records to gauge what might have been a significant EMF exposure for local residents prior to the onset of the cancer cluster. Infectious Diseases in Leukemia Clusters Wiemels also wants to explore possible links between the leukemia cases and infectious disease outbreaks. He will be analyzing Navy records and Nevada disease registries. He also will be looking at bone marrow samples taken at the time of diagnosis. In Japan and parts of Africa, a certain form of leukemia is linked to chronic infection with a retrovirus called HTLV-1. There also are viruses that trigger leukemia in cats, cattle, mice and birds. But thus far, no infection has been linked to acute lymphoblastic leukemia in humans. If an outbreak of infection did contribute to the Fallon leukemia cluster, it would not necessarily leave traces in preserved bone marrow tissue. But if infection was chronic and active at the time of leukemia diagnosis, there might be bits of microbial genetic material in the samples. Wiemels and colleagues will look for virus particles in sample tissue under an electron microscope. In addition, Wiemels plans to take advantage of the unique ViroChip developed by UCSF molecular biologist Joe DeRisi, PhD. In the ViroChip, microscopic spots with bits of genes representing all known human viruses are indexed and arrayed on a plate - like a microscope slide. An automated laboratory test allows researchers to determine whether their biological samples contain matching DNA that points to the presence of a particular virus. Wiemels also will be more closely examining the genetic fingerprints of leukemia cells from the different cluster cases. He will look for any shared, distinctive genetic alterations that might be the disruptive modus operandi wrought by a specific infectious agent. At a minimum, Wiemels expects this research to generate more ideas for testing. "I believe it would be irresponsible not to try to turn over a few more stones," he says.

 

Related Links

Joseph L. Wiemels, PhD

UCSF Comprehensive Cancer Center

Cancer Clusters

Centers for Disease Control and Prevention

Leukemia Cluster: Churchill County (Fallon) Childhood Leukemia

Nevada State Health Division

Children of Cancer portal

Reno Gazette-Journal

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