From 1961 to 1982, Centers for Disease Control and Prevention (CDC) investigated 108 reported cancer clusters in 29 states and 5 foreign countries (1). The studies were begun in hopes of identifying a viral cause of cancer clusters. During these investigations, however, no clear cause was determined for any of the reported clusters.
Cancer cluster investigations are complex and difficult for several reasons. Although any cancer case is one too many, suspected cancer clusters often do not contain enough cases for investigators to do a meaningful statistical analysis or reach a conclusion. Determining the cause of cancer is complicated because exposure to cancer-causing agents may have occurred many years before diagnosis. Therefore, assessing the amount and type of cancer-causing agents an individual has been exposed to is difficult. Unfortunately, cancer is often the result of a combination of agents and risk factors that interact in a way that science does not yet fully understand (2).
Below is the short list of cancer clusters in the United States that were thoroughly studied by epidemiologic investigations.
1963-1999, 56 people affected by lung cancer or mesothelioma in Libby, Montana. Suspected cause tremolite. (3).
1967-1973, 4 people affected by liver angiosarcoma in Louisville, Kentucky (4). Suspected cause vinyl chloride monomer (4).
1968-1995, 103 people affected by leukemia or lymphoma in Camp Lejeune, North Carolina. Suspected cause trichloroethylene (5).
1973-1982, 16-29 people affected by brain or CNS cancer in Cooke County, Texas. The cause is still unknown (6).
1979-1996, 40 people affected by brain or CNS cancer in Toms River, New Jersey. Suspected cause SAN trimer, styrene, acrylonitrile (7).
1981-1986, 21 people affected by leukemia in Woburn, Massachusetts, (21). Suspected cause: chloroform, tetrachloroethylene, trichloroethylene, 1,2-dichloroethene, arsenic (8).
1987-1999, 20 people affected by brain cancer, leukemia or lymphoma in Wilmington, Massachusetts. Suspected cause N-nitrosodimethylamine (9).
Two recent studies deserve more attention as they shed light on another factor that may be partially responsible for the occurrence of cancer clusters.
From 1997 to 2001, doctors in Churchill County found that 15 children had leukemia. This number was higher than usual. Beginning in 2002, the Nevada State Health Division and the Centers for Disease Control and Prevention (CDC) worked together to try to learn why so many children in Churchill County were getting sick. One test found that people who lived in Churchill County had higher amounts of two chemicals in their blood and urine than did people from other areas. The two chemicals were tungsten and arsenic. However, the higher amounts were found in children with leukemia and in children without leukemia (10, 11).
Another cluster was indentified in Sierra Vista, Arizona, where from 1995 to 2003, 11 children in were diagnosed with leukemia. Because this number of cases was higher than expected, the Arizona Department of Health Services and the Cochise County Health Department asked the Centers for Disease Control and Prevention (CDC) to help them try to learn why these children got sick. CDC’s National Center for Environmental Health tested blood and urine samples from some people in Sierra Vista to measure levels of chemicals in their bodies. The results of the study showed that levels of chemicals found in most study participants were lower than levels in the U.S. population. The levels of chemicals were not different between case and comparison families (12).
However, in both studies CDC scientists found a variation in a gene called SUOX. All of the children with leukemia had this variation in the SUOX gene, and almost half of the children who did not have leukemia had that same variation. This means that even if the variation in the SUOX gene adds to the risk for leukemia, it has to be noted that there must also be other factors involved. The direct cause of most leukemias still remains unknown, and scientists are still are not sure why so many children in both cancer clusters got leukemia (10, 11, 12).
Although no clear cause was reported for any of the cancer cluster, scientists documented 15 most commonly used environmental exposure terms found in articles pertaining to cancer clusters published in U.S. newspapers from 1977 to 2001 (13).
Disease clusters continue to concern the public, and public sentiment that environmental causes are responsible and must be investigated is widely prevalent. More than thirty years ago, the Centers for Disease Control and Prevention (CDC) recognized the need to develop operating procedures for response to public concern about disease clusters. In 1990 CDC released the “Guidelines for Investigating Clusters of Health Events” (14) in which a four-stage process was presented: a) an initial response to gather source information, b) an assessment of the occurrence of the health event, c) a feasibility study, and d) an epidemiologic investigation. During the last years, these guidelines have provided a framework that most state health departments have adopted, modifying it for their specific situations and available resources.
The states have the primary responsibility for response to cancer cluster concerns within their domain. State and local health departments respond to cancer cluster reports and inquiries about suspected clusters. Most state health departments’ strategies for cluster response are based on CDC’s “Guidelines for Investigating Clusters of Health Events” with some modifications. Usually, a local or state health department starts by gathering information about the suspected cancer cluster including expected cancer rate, types of cancer, number of cases, and the age, sex, race, address, occupation, and age at diagnosis of the individuals with cancer. Information may be verified by contacting patients and relatives or by obtaining medical records. This information is then compared to census data and state cancer registry data to determine if there is a higher than expected number of cases. Most investigations do not proceed beyond evaluation of the gathered information; however the local or state health department may perform a more intensive assessment or comprehensive epidemiological study. The decision to proceed to a more intensive investigation is usually based on a set of rules developed by the health department.
National Center for Environmental Health (NCEH) of CDC becomes involved when state health departments request assistance. NCEH response has ranged from consultation with appropriate staff to active participation in an epidemiologic or biosampling investigation. In some cases, NCEH has provided assistance by conducting analysis of biological samples and storing them for future study, as it did in the childhood leukemia clusters in Churchill County, Nevada and Sierra Vista, Arizona (11, 12).
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References:
1. Caldwell GG. Twenty-two years of cancer cluster investigations at the Centers for Disease Control. Am J Epidemiol 1990; 132[1]:S43-S47
2. CDC
3. McDonald, JC. Harris, J. Armstrong, B. (2004). Occupational and Environmental Medicine 61 (4), 363–366.
4. Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report. (Feb. 7, 1997). Epidemiologic Notes and Reports Angiosarcoma of the Liver Among Polyvinyl Chloride Workers -- Kentucky. 46 (5), 97–101.
5. US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry (ATSDR). (Jul. 2003). Survey of Childhood Cancers and Birth Defects at USMC Camp Lejeune. Retrieved Jan. 31, 2005
6. Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report. (August 24, 1984). Brain Cancer -- Texas 33 (33), 477–479.
7. New Jersey Department of Health and Senior Services, Hazardous Site Health Evaluation Program, Division of Epidemiology, Environmental and Occupational Health, & US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry (ATSDR). (Sep. 1997). Childhood Cancer Incidence Health Consultation: A Review and Analysis of Cancer Registry Data, 1979-1995 for Dover Township (Ocean County), New Jersey
8. Costas, K. Knorr, RS. Condon, SK. (Dec. 2, 2002). A case–control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water. Science of The Total Environment 300 (1-3), 23–35.
9. Massachusetts Department of Public Health. (2002). Wilmington Childhood Cancer Study. Bureau of Environmental Health Assessment. Retrieved Jan. 31, 2005.
10. National Center for Environmental Health, Centers for Disease Control and Prevention. (2004). Cancer Clusters - Churchill County (Fallon), Nevada Exposure Assessment. Retrieved Jan. 31, 2005.
11. http://www.cdc.gov/nceh/clusters/fallon/genetictesting.htm
12. http://www.cdc.gov/nceh/clusters/sierravista/default.htm
13. Beverly S. Kingsley, Karen L. Schmeichel, and Carol H. Rubin.: “An Update on Cancer Cluster Activities at the Centers for Disease Control and Prevention”, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Environmental Health Perspectives • VOLUME 115 | NUMBER 1 | January 2007
14. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001797.htm
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