Cancer Clusters, Part 2

by National Cancer Institute

(Page 2 of 2)

Accurately defining the group of people who should be considered "at risk" is important when investigating a possible cancer cluster. One of the greatest problems in defining clusters is the tendency to expand the geographic borders of the cluster to include additional cases of the suspected disease as they are discovered. The tendency to define the borders of a cluster on the basis of where known cases are located, rather than to first define the population and geographic area and then determine if the number of cancers is excessive, creates many "clusters" that are not real.

Epidemiologists must also consider that a confirmed cancer cluster may not be the result of any single, external cause or hazard. A cancer cluster could be the result of chance, an error in the calculation of the expected number of cancer cases, or differences in the case definition between observed and expected cases. Moreover, because people change where they live from time to time, it can be difficult for epidemiologists to identify previous exposures and find the medical records that are needed to determine the kind of cancer a person had-or if it was cancer at all.

Because a variety of factors often work together to create the appearance of a cluster where nothing abnormal is occurring, most reports of suspected cancer clusters are not shown to be true clusters. Many reported clusters do not include enough cases for epidemiologists to arrive at any conclusions. Sometimes, even when a suspected cluster has enough cases for study, a greater than expected number of cases cannot be demonstrated. Other times, epidemiologists find a true excess of cases, but they cannot find an explanation for it. For example, a suspected carcinogen may cause cancer only under certain circumstances, making its impact difficult to detect.

Genetics and Environment

Because most cancers are thought to be caused by a combination of factors related to genetics and environment (including behavior and lifestyle), studies of suspected cancer clusters usually focus on these two issues. Genetic factors are inherited, that is, passed from parents to children. However, establishing a genetic-environmental interaction (significant and valid evidence that a specific genetic factor leads to an increased chance that a particular environmental exposure will result in cancer) requires studies of large populations over long periods of time. Researchers are just beginning to learn about the roles genetics and environmental exposures play in carcinogenesis. Some of their discoveries are outlined below:

Genetics

All cancers develop because of genetic alterations of one kind or another. An alteration is a change or mutation in the physical structure of a gene that interferes with the gene's normal functions.

Some genetic alterations that increase the risk of cancer are present at birth in the genes of all cells in the body, including reproductive cells. These changes, which are called germline mutations, can be passed from parent to child. This type of alteration is known as an inherited susceptibility; most cancers are not due to an inherited susceptibility.

Most cancers result from genetic changes that occur after birth during one's lifetime. Genetic changes can occur in any cell that divides. These genetic changes are called somatic alterations.

Familial cancer clusters (cancer that occurs in families more often than would be expected by chance) have been reported for many types of cancer. Because cancer is a common disease, it is not unusual for several cases to occur within a family. Familial cancer clusters are sometimes linked to inherited susceptibility, but environmental factors and chance may also be involved.

Having an inherited susceptibility for a type of cancer does not necessarily mean that the individual will be diagnosed with the cancer; it means the chance of developing cancer increases if other factors that promote the development of cancer are present or are encountered later.

Environment

The term environment includes not only air, water, and soil, but also substances and conditions in the home and workplace. It also includes diet; the use of tobacco, alcohol, or drugs; exposure to chemicals; and exposure to sunlight and other forms of radiation.

People are exposed to a variety of environmental factors for varying lengths of time, and these factors interact in ways that are still not fully understood. Further, individuals have varying levels of susceptibility to these factors.

Hazardous substances are often found in higher levels in the workplace than in the general environment. For this reason, some workers may have greater and longer exposures to such substances than the general population. Findings of higher than expected numbers of cancer cases among workers in particular occupations or industries provide important leads regarding causes of cancer among the general public. In fact, occupational studies (studies of specific groups of workers) have identified many specific cancer-causing substances and have provided the motivation to find ways to reduce or eliminate exposures in the workplace and elsewhere.

Reporting Suspected Cancer Clusters

A suspected cancer cluster may be reported to a state or local health department or state cancer registry. State and local health departments and cancer registries use established criteria to investigate reports of cancer clusters. When a suspected cancer cluster is first reported, the investigating department or agency gathers information and gives the inquirer general information about cancer clusters. Although investigators may use different processes, most follow a basic procedure in which increasingly specific information is obtained and analyzed in stages. Investigators are likely to request the following:

Information about the potential cluster: type(s) of cancer, number of cases, suspected exposure(s), and geographic area/time period of concern.

Information about each person with cancer in the potential cluster: name, address, telephone number, gender, race, age, occupation(s), as well as area(s) lived in/length of time.

Information about each case of cancer: type of cancer, date of diagnosis, age at diagnosis, possible causes, metastatic sites, and physician contact.

Most reports of suspected cancer clusters are resolved at this initial contact because concerned individuals realize that what seemed like a cancer cluster is not a true cluster. If further evaluation is needed, epidemiologists will take the following steps to investigate a possible cancer cluster:

Attempt to verify the reported cases by contacting patients and relatives and obtaining medical records.

Compare the number of cases in the suspected cancer cluster with information in census data and cancer registries to determine if there is a higher than expected number of cases.

Review the scientific literature to establish whether the reported cancer(s) have been linked to the suspected exposure.

Work with Federal agencies, if necessary, to gather additional information to help decide whether to conduct a comprehensive epidemiological study.

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