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Full text of "Evaluation of cancer cluster reports in North Carolina"

A SPECIAL REPORT SERIES BY THE N.C. DEPARTMENT OF ENVIRONMENT, HEALTH, AND NATURAL RESOURCES, 
DIVISION OF STATISTICS AND INFORMATION SERVICES, CENTER FOR HEALTH AND ENVIRONMENTAL STATISTICS, 

P.O. BOX 27687, RALEIGH, N.C. 27611-7687. 



No. 56 



April 1991 



EVALUATION OF CANCER CLUSTER REPORTS 
IN NORTH CAROLINA 



by 



Tim E. Aldrich, Ph.D. 

Julius Lindsey 

Peter Morris, M.D. 



ABSTRACT 

North Carolinians have long been concerned about the patterns of cancer occurrence in the state, 
especially those that signal a potential environmental risk. Being increasingly faced with the task of 
responding to citizen reports of apparent cancer clusters (defined as the occurrence of an increased rate of 
cancer in a small area or within a short period of time), the North Carolina Department of Environment, 
Health, and Natural Resources implemented a formal program for the evaluation of the cluster reports in 
1982. Mounting volume of cancer cluster reports and limited resources resulted in the development of a 
revised protocol involving the Cancer Surveillance Section of the Division of Statistics and Information 
Services and use of more databased evaluation procedures. 

This report provides an overview of the current procedures in use for evaluating cancer cluster reports 
in North Carolina and highlights a few of the most interesting cluster evaluations over the last sixteen 
months. Since September 1989, forty-nine reports of cancer clusters have been received from thirty-one 
counties. Twenty-seven of these reports have been evaluated and closed. Eleven cluster reports are 
currently in the process of active evaluation and another eleven are awaiting the start of evaluation 
activities. Of the closed reports, five indicated increased cancer occurrence with three of the five 
potentially providing additional clues to environmental risk factors. 



INTRODUCTION 

A cancer cluster is the occurrence of a greater than 
expected number of cases of cancer within a small 
geographic area and/or within a short period of time 
(i.e., 3-5 years). Cancer clusters are usually reported 
when people learn that several friends, family 
members, neighbors or co-workers have been 
diagnosed with cancer. Because cancer is such a 
common disease, it is important to discover whether 
the cancers that have been observed truly represent 
the occurrence of more cases than one would expect. 

The evaluation of cancer cluster reports may help 
to determine specific causes of cancer or to identify 
risks for cancer in the environment (Caldwell, 
1989). Cancer cluster reports also serve an important 
social service as well by assuaging public anxiety over 
potential environmental cancer risks in their 
community (Fiore, et al., 1990). Nearly all state 
health departments have developed a protocol for 
investigating cancer cluster reports. The procedures 
vary greatly, but each mechanism attempts to respond 
to very real public concern (Warner and Aldrich, 
1987; Thacker, 1989). 

With the establishment of the Environmental 
Epidemiology Section in October, 1982, North 
Carolina began a formal process for evaluating of 
cancer cluster reports. This effort was enhanced by 
the re-establishment of a statewide cancer registry in 
1988. 

Classifying Cluster Reports 

Cluster reports are divided into three broad 
categories: SUSPECTED clusters, REAL clusters 
and MEANINGFUL clusters. 

SUSPECTED CLUSTERS: When a person reports 
a perceived increased cancer occurrence in a small 
geographic area, but none is found to exist, then this 
report is categorized as a "suspected" cluster. These 
reports are not really clusters at all. The observed 
cases may appear to represent a cluster partly 
because cancer is so common (i.e., it strikes one of 
four people sometime during their lifetime). 
"Suspected" cluster reports represent about 
seventy-five percent of all cancer cluster reports 
received. 

REAL CLUSTERS: When significantly more 
cancers occur than would be expected within a small 
geographic area and/or in a short time period, then a 
"REAL" cluster is said to exist. However, a REAL 



cluster is one for which there is no pattern to the 
increase that can suggest an interpretation of potential 
increased risk. These REAL clusters will occur 
periodically, simply by chance. For Example: 

In one of every 256 families of four, all four 
members will have cancer sometime during 
their lifetime, by chance alone. Assuming a 
100-year lifetime, one family of four out of 
25,600 families of four could all develop 
cancer in a single year. That would be a 
REAL cluster, but it would be due to chance. 

REAL cluster reports are often found in communities 
where there is a large percentage of older persons. 
Cancer rates increase with age and adjusting for age 
often explains the observation of higher than expected 
number of cases. REAL cluster rejxjrts represent 
about twenty percent of all reports received. 

MEANINGFUL CLUSTERS: When a cluster is 
shown to be "REAL" and there is a pattern to the 

increase that suggests a group of people at unusually 
high risk of cancer, then that cluster is classified as 
"MEANINGFUL." These cluster reports comprise 
about five percent of all cluster reports received and 
are the ones that lead to further epidemiologic 
studies. 

BACKGROUND 

Historically, the North Carolina cancer cluster 
evaluation protocol operated from the Environmental 
Epidemiology Section of the Department of 
Environment, Health, and Natural Resources. 
Evaluations of reports of cancer clusters were 
generally rigorous scientific activities featuring 
extensive field work, often including interviews and 
environmental sampling. Some of the routine 
procedural steps are noted in the discussion of the 
current protocol (see below). All cluster reports 
were acknowledged, but usually, only two or three 
studies were able to be mounted in a single year. This 
protocol was first used in 1 982 when the Environmental 
Epidemiology Section conducted a cancer cluster 
study in Cherokee and Macon counties. That study 
was both time-consuming and incomplete, as only 
mortality data were available for the statistical 
analysis of the study population. The findings from 
the investigation were equivocal. 

Following that experience, the Environmental 
Epidemiology Section joined with representatives 
from universities and the scientific community to 
undertake a study of the cancer database needs for 



responding to environmental health concerns. With 
funding from the Office of Technology Assessment, 
this group investigated the cancer databases in other 
states and recommended that North Carolina 
establish a population-based cancer registry 
( Aldrich, et al., 1989). The registry was funded and 
is located in the Division of Statistics and Information 
Services of the Department of Environment, Health, 
and Natural Resources. When the registry became 
functional (Fall, 1989), the Environmental 
Epidemiology Section began negotiations leading to 
a revised protocol for use in the evaluation of cancer 
cluster reports (see Figure 1). This protocol was 
implemented gradually through the Fall of 1989 and 
became fully operational on January 1, 1990. The 
experience upon which the present report is based 
spans the entire sixteen month period from 
September 1, 1989 to December 31, 1990. 

MATERIALS AND METHODS 

In North Carolina, suspected cancer clusters may 
be reported to county health departments, the state 
health department, a physician, the Central Cancer 
Registry, or the American Cancer Society. Wherever 
reports are initially received, they are forwarded to 
the Cancer Surveillance Section for evaluation. 
These evaluations consist of ten basic steps (NOTE: 
An asterisk indicates the step was also a pan of the former 
protocol). 

Step 1: A letter acknowledging receipt of the 
report.* The person reporting a possible 
cancer cluster receives written verification 
of their report. This letter includes a 
description of the steps that will be followed 
in the evaluation and an estimate of the 
time frame involved. Copies of the letter 
are sent to the Environmental Epidemiology 
Section and to the appropriate county 
health department. 

Step 2: Verification of reported cases and a 
search for additional cases.* A critical 
step in the cluster evaluation process is 
identifying all cancer cases in the study 
area. Relying solely on the respondent's 
report of cases is not adequate. It is extremely 
important to verify the accuracy of the 
diagnosis for the reported cases and to 
determine if any cases are missing. Prior to 
1988 a search for cancer cases through 
hospital records and local doctors' offices 
had to be conducted. In a few communities, 
surveys of residents have been performed 
to seek additional cases. These instances are 



usually those involving small communities 
or communities where a large number of 
the cancer cases are likely to be still living. 
After 1987, cancer cases can be ascertained 
from the Central Cancer Registry for many 
counties (all North Carolina counties will 
be completed in the database for 1990 cases 
and subsequent years). 

Step 3: Ascertainment of mortality data for the 
prior twenty years.* The purpose of this 
step is to determine what the trends in 
mortality rates have been in and around the 
specified area. Some regions of North 
Carolina have experienced elevated rates 
for specific cancers for many years; generally 
these are multiple county areas and represent 
an objective of research independent of 
cancer cluster reports. The results of these 
mortality analyses may influence whether 
or not a decision is made to proceed with 
the evaluation of a cluster report, e.g., a 
cluster report may represent recognition of 
a regional trend that is already under study. 

This is also a point when adjusting for age 
explains many cluster reports received from 
areas of the state where there are large 
numbers of older, retired citizens. Race and 
sex specific age-adjusted mortality rates for 
thirty-two cancer sites have been calculated 
for all 100 counties of North Carolina for 
1970 through 1989. Because many cancers 
are quite rare and many county populations 
quite small, these rates must be interpreted 
cautiously. 

Step 4: Crude estimation of cancer incidence. As 

cancer survival increases, mortality data 
alone becomes less appropriate in deter- 
mining whether further evaluation of a 
cluster report is justified. Thus, the incidence 
of cancer in communities reporting clusters 
must often be ascertained. Beginning in 
1990, the Central Cancer Registry collects 
incidence data on all new cancer cases 
statewide, so that in the future estimates of 
these rates will no longer be necessary — the 
actual rates will be available. For studies of 
reported clusters prior to 1990, an estimate 
of the expected number of cases is made 
(using national rates) to determine what the 
expected number of cancer cases would be; 
this may then be compared to the number 
of cancer cases identified in study area (see 
Step 2). 



Step 5: Statistical analysis of the incidence and 
mortality data. The computer software 
CLUSTER was developed in North Carolina 
with federal funding from the Agency for 
Toxic Substances and Disease Registry 
(Aldrich, 1990). This computer program 
provides twelve different statistical tests for 
analyzing the patterns of occurrence for 
rare health events. When the observed 
number of cancer cases greatly exceeds the 
number of cases expected, this is one 
criterion that a cluster exists. Because many 
cancers are quite rare, an "increase" may 
sometimes only involve two or three cases; 
special statistical methods are used for 
studying these rare events. Similarly, an 
overall cancer rate may not be elevated 
(e.g., for a whole county), but one subgroup 
of the population may be experiencing 
more cancer cases than they should (e.g., a 
single neighborhood, black women, etc.), 
based on the population in the community. 
Analyses by population subgroup are a part 
of the CLUSTER capabilities, as well as 
studies of spatial patterns and time trends 
among cancer cases. 

Step 6: Review of the relevant scientific 
literature.* As one step for evaluating each 
cancer cluster report, scientific articles are 
reviewed. The articles studied are related to 
the particular cancers that may comprise 
the reported cluster. Also, scientific articles 
will be reviewed related to health effects 
from exposure to an agent or an exposure 
source that the community may cite as a 
part of the cluster report. Cancer is 
comprised of many diverse disease processes 
and there are many hypotheses for risk 
factors for virtually all cancers. Identifying 
known and suspected risk factors of specific 
cancers can guide the evaluation of a cluster 
report to exposures which might not 
otherwise have been suspected. State agency 
records are accessible during a cluster 
evaluation for determining the location of 
specific industries or hazardous waste sites, 
particularly those from which there are 
potentially carcinogenic emissions. 

If cluster report evaluations are to serve 
as a means for identifying new environmental 
risk factors for cancer, a necessary step is to 



assess the presence of risk factors which 
may already have been identified from 
other cluster studies. Similarly, the results 
of MEANINGFUL cluster reports are 
published whenever possible so that 
researchers in other states can be informed 
of what risk factors may have been identified 
from North Carolina's cancer cluster 
reports. 

Step 7: A site visit is always made to the location 
reporting a cancer cluster (whether citizens 
are contacted or not). These visits are made 
in the course of routine travel related to 
Central Cancer Registry operations, not as 
trips solely for visiting a cluster community. 
This approach to site visits is based largely 
on financial considerations; as such it can 
lead to some cluster sites being visited 
sooner than others. On the site visit, a map 
is prepared of the entire geographic area, 
highlighting the source locations of potential 
hazardous exposures. Often, the environ- 
mental source identified by the citizen 
reporting the cluster is not as "remarkable" 
as another one that they may not even be 
aware exists. 

This is a point in the cluster evaluation 
where the literature review may play a 
pivotal role; suggested risk factors men- 
tioned in the literature may be unknown to 
the citizen. This is also when community 
education is a consideration; many cancers 
have recognized lifestyle, age-specific and 
genetic risk factors and may have little 
relation to environmental exposures. Such 
cancers as lung and breast cancer may 
comprise the majority of cases that the 
citizen reports in the cluster; yet a few rare 
cancers may represent more meaningful 
envirorunentally-related events. For these 
reasons, all cluster report sites are visited; 
most visits are dead ends (hence visits are 
made at the convenience of stafO, but 
occasionally a previously unsuspected 
environmental hazard is identified. That is 
also why it is important that all cluster 
reports be evaluated; the increased number 
of cancer cases that offer a clue to 
environmental cancer risks may not be 
those that drew the informant's attention 
to report the cluster. 



Step 8: On-site meeting with area residents (if 
requested).* This is the point at which 
educational information is provided to 
residents about their cluster report and 
about cancer in general. These educational 
sessions are always coordinated with local 
health agencies (e.g., county health 
department, American Cancer Society). 
This coordination is a effort to promote 
broader and continuing cancer educational 
activities for local communities. 

Step 9: Final report of conclusions and recom- 
mendations* These reports are provided 
to all parties associated with the cluster 
(e.g., county health department); these 
reports are "public" documents, available 
to all who request a copy. Some reports are 
quite detailed, while others are relatively 
brief, depending on the availability of data 
and the findings of the evaluation. The 
information related to personal histories, 
like all individual records, are confidential. 

Step 10: Entry into a continuing file of Cluster 
Reports. All communities that report a 
cluster become a site for continuing 
surveillance. Based on the statewide database 
being created through the Central Cancer 
Registry, the cancer experience for each 
community will be monitored for a 
minimum of five years. The specific cancers 
that comprised the cluster report will be 
studied, as will other cancers that may have 
a relation to environmental exposures. 

Close attention is paid when a second 
cancer cluster report is received from the 
same or a nearby community. The previous 
cluster file will be reviewed and the maps 
prepared from earlier site visits are inspected. 
Occasionally, cluster reports will be 
evaluated simultaneously from neighboring 
areas, which can provide a cost savings as 
well as a more productive process for 
evaluating disease patterns. 

The duration or timing of the steps of the 
evaluation protocol may vary with the individual 
' cluster report; however, the sequence is always 
maintained (Figure 1). All cancer cluster report 
evaluations are monitored through periodic activity 
reports, of which this report is one. When a cluster 
evaluation results in inconclusive evidence of 
clustering, the community represented by the cluster 



report will be kept under surveillance for a minimum 
of five years. When an evaluation indicates a 
potentially MEANINGFUL increase in cancer 
occurrence, it is referred to the Environmental 
Epidemiology Section for further investigation. 
Subsequent investigations usually include detailed 
case reviews and on-site interviews, and if necessary, 
environmental sampling and monitoring of relevant 
residential exposures. In some instances, a grant 
proposal may be prepared to seek federal funds to 
facilitate further study of the reported cluster. 

RESULTS 

Between September 1989 and December 1990, 
fifty-two disease cluster reports have been received 
from thirty-one counties throughout North Carolina. 
Forty-nine of these reports related to cancer (Table 
1 ) and three involved other health events (Table 2). 
In addition, four re-evaluations of cluster studies 
from prior years were conducted. 

Of the forty-nine cancer cluster reports, the 
Cancer Surveillance Section evaluated forty-three 
and six reports were managed by others — one by the 
Environmental Epidemiology Section; one by a local 
physician from Washington County who reported a 
potential cluster of colon cancer cases; two by the 
epidemiologist in the Guilford County Health 
Department; one by a University of North Carolina 
researcher (Dr. Carl Shy); and the final one by a 
graduate student from the Bowman-Gray School of 
Medicine. Twenty-seven of these cluster reports 
have been closed, eleven are still in active study and 
another eleven are awaiting the start of active 
evaluation ("Pending"). Of the closed reports, five 
were determined to be REAL clusters of which three 
were deemed to be MEANINGFUL. Each of these 
five cluster evaluations are described below: 

Brain Cancer in Rowan County — This repent 
was suiTmitted fry a local ph-jsxcian who believed Ke had 
seen an increase in the brain cancer cases in his medical 
practice. Following this report, the Environmental 
Epidemiology Section reviewed 260 medical histories (in 
seven hospitab) over the next year which represented all 
new brain caruxr cases for Rowan County arui its 
neighboring counrie5 from 1980 to 1989. The case 
histories include details of the tumors (dates of diagnosis, 
cell types) arui any krwwn risk patterns (age, occupation, 
srrwking history, etc.). Several cases initially identified by 
the informant were excluded from the "cluster" because 
the caru^er of the brain reported to the investigators was 
spread to the brain from other body sites, or because the 
person was diagnosed with brain career prior to moving to 
Rowan County. 



Statistical aiuilyses iiuiicated that an unusual pattern 
of brain cancer incidence had occurred in Rowan County, 
although not an increased rate of disease (Table 3). For 
eight of the years of the eighties, very feu> brain cancer 
cases occurred in the "cluster area." But in 1985 and 
J 989, most of the Rowan County brain cancer cases 
occurred in the ' 'cluster area. ' ' For the county as a whole, 
however, no overall increase in brain cancer occurred. 
The observed ' 'sudden ir^rease' ' actually followed periods 
of low occurrence. This pattern of brain cancer occurrerux 
did not suggest an environmental risk. The study results 
were presented by written report and through a local press 
conference. 

Brain Tumors in 'Northampton County — This 
report was submitted by the county health director who 
was concerned about irurreased occurrerv:e of brain tumors 
ar\d the possible association with a local industry. A 
literature review iruiicated that the relationship to the 
suspected industry was plausible aixd had been observed 
by others (Rabotti, et al, 1966; Morantz, et al, 1985). 
Community residents assisted health department personnel 
in identifying living brain tumor cases; the Cancer 
Surveiilance Section performed a parallel search for 
deceased cases. 

An inspection of the 1 984-89 observed-versus-expected 
case pattern indicated eighteen brain tumors occurred 
when twelve were expected. The race-sex pattern was not 
coTuistent with the ruitional pattern run with the county's 
population characteristics. A subset of four cases occurred 
in proximity to the suspect iruiustry. The possibility that 
these cases represented the increase could not be dismissed, 
and as a result, this cluster was referred to the 
Environmental Epidemiology Section for further study. 

Pediatric Cancer in Gaston County — This 
cluster report was submitted by the parent of one of three 
cases of a rare pediatric tumor believed to have occurred 
in a short period of time in a small municipality in Gaston 
County. The search for additioruil cases from 1 970 to 
1 989 iruiicated that there were two of these rare pediatric 
caru:er cases in the mid-seventies followed by an eleven- 
year hiatus and then six cases in the r\ext 30 months. 
These latter cancer cases were the subject of the study. A 
review of the scarce literature for this tumor revealed that 
researchers in hlorth Carolirw. had previously identified 
the iruyeased rates for this car\cer wthin a tu^elve-county 
re^on {Crruffevman, et al. , 1 982). 

The statistical aruilysis by the Cancer Surveillarux 
Section iruiicated that the cases were not randomly 
distributed. Sorrxe of the previously identified risk factors 
for this carKer were also fourui with these cases. Since 
these cases involved children, the distribution of birth 
defects in Gaston County was also examined using data 



from the N.C. Birth Defects Registry. No geographic 
clustering was observed for birth defects. Despite this 
firuiing, the presence of several large iruiustries and two 
recognized hazardous waste sites in proximity to several of 
the caivxr cases led to this cluster being referred to the 
Environmental Epidemiology Section for further study. 

Non-Hodgkin's Lym.phonia in Granville 
County — A county commissioner referred this potential 
caru:er cluster to the Cancer Surveillarxce Section. The 
residents of this small community u«re quite cxmcemed 
about an overall iru:rease in cancer, but especially Non- 
Hodgkin's Lymphorrui (NHL). The aruilyses of the 
Granville County mortality experience revealed that their 
rates were rujt elevated over those of the state. Con- 
sequently, further evaluation activities by the state would 
ru}t be pursued. Upon hearing of these firuiings however, 
local residents organized a citizen's task force to extend 
the data aruxlyses further by collecting cancer irKideru:e 
data for 1 975 to 1 989. This u^ell-organi^ed community 
effort identified over 1 30 cancer cases, nine of which were 
rum-Hodgkin's lymphomas. The citizen's task force also 
collected emissions data for a dozen local iruiustries. 

Using the citizen-identified cases, a REAL increase for 
lymphoma occurrence was fourui, but there was ruj 
particular spatial or temporal pattern for the cases. There 
was abo a visually identifiable aggregate of colon caruxr 
cases, but overall there was no iru:rease in colon caruxr 
occurrence. Norxe of the cancer patterns could be linked to 
any of the paths of iruiustrial emissUms; arui only one 
company was determined to represent a potential hazard. 
This cluster report was closed with the assurarxce that 
surveillaru:e would be maintair\ed for this community. 
While the work of the citizen's task force did not change 
the firuiings regarding cancer clustering, it did provide 
better data for the aruilysis arui a further opportunity for 
education to the community about cancer. 

Colon Cancer in New Hanover County — The 

county health director reported this cluster of four 
intestinal caruxrs arrumg neighbors, living in extremely 
close f>roximity. Three of the four colon car\cer cases were 
urxder 65 years of age, an unusual distribution for caruxr 
at this aruitomic site. This region of the state has been the 
focus of much study because of drinking water con- 
tamination (e.g., trihalometharie formation). Eachofthe 
residents' drinking water was taken from a private well 
which was suspected to be contamiruited with hydrogen 
sulfide. This cluster report was referred to the 
Environmental Epidemiology Section for testing of the 
drinking water supplies. In light of the proximity of 
another "closed" cluster report to this one, a 
recommeruiation was also made that surveillarux be 
nmintained for cancer occurrerux in both of these 
communities. 



In addirion to the study of cancer clusters, the 
Cancer Surveillance Section and the Environmental 
Epidemiology Section perform special studies and 
apply for federal grants to fund large research efforts 
in North Carolina. A special study of brain cancer in 
North Carolina is in progress. The information from 
both the Rowan and the Northampton clusters 
figures significantly in the design of that research 
effort. A federal grant proposal is being prepared to 
conduct a more thorough study of the several 
counties potentially involved in the rare pediatric 
cancer cluster in Gaston County and of the 
environmental hazards identified through that 
investigation. Finally, a large study of leukemia 
patterns in the state is also under way; this is 
associated with findings from several cluster report 
evaluations. 

FOLLOW-UP OF CLOSED CANCER 
CLUSTER REPORTS 

With the additional capabilities that are now 
available for the statistical analysis of cancer cluster 
reports, and because of the continuing interest 
expressed by three of the communities that had 
reported earlier cancer cluster reports, three evalua- 
tions for cancer clustering were re-analyzed for this 
report. Also, a search for evidence of leukemia 
clustering was repeated due to continuing interest by 
the Environmental Epidemiology Section. 

Leukemia in Cherokee County — Local residents 
suspected increased cancer occurrence due to the aerial 
spraying of herbicides in the forests of western North 
Carolina. Researchers evaluated the pattern of mortality 
for Cherokee County and seven surrounding counties 
using statistical tests. No pattern of increased cancer 
occurrence u>as found to be associated udth any potential 
environmental hazard. TKe finding of a generalized 
increase in all cancers for two counties (Cherokee and 
}sAacon) led to a recommendation of further study, with 
an exparxded time period. 

The Cancer Surveillance Section re-analyzed the 
leukemia data for these eight counties arui extended the 
aruilyses up to 1988 (Table 4). Macon Counfy had two 
time periods that showed evidence of temporal clustering, 
1979-81 and 1987-88. For Cherokee and Haywood 
counties as well as the region as a whole, the years 
1980-81 also showed increased leukemia rrwrtality. It is 
intriguing that the cancer occunerice for the years 1 980- 
81 of the previous study was the basis upon which a 
follow-up aruilysis was recommeruied; yet these very years 
(1980-81) may rww be seen to represent the peak of 
leukemia occurrerice for the region. It will be interesting to 
monitor future cancer patterns for these counties. 



Leukemia ai\d Lymphoma in Burke County — 

Researchers from the Vnwersity of North Carolina 
corxducteda "rxearest-rKighbor" arwdysis of several caruxr 
cases in Burke County for the period 1970-79. Their 
results did not indicate clustering for leukemia or 
lymphomas as reported by citizens. Clustering of lung and 
prostate carxcers was found, however. The CDC also 
evaluated this leukemia /lymphorrux pattern and/ound no 
evidence of increased occurreru:e. 

The Cancer Surveillance Section analysed the 
lymphorrwL iruidence data for Burke County for the 1 980- 
89 period. There is still no eviderxce of iruyeased 
occurrerxce, hut the ten-year pattern is interesting. Of the 
fourteen cases in these ten years, eight occurred in 1 980- 
82 (three, three and two cases respectively). Two of the 
1 980 cases lived close to each other, but none of the others 
lived particularly close, nor was there any unusual age, 
race or sex pattern evident. The fact that two cases lived 
near the location of the earlier suspected cluster is also 
notable. Further surveillaru:e of the leukemia and 
lymphoma patterrxs in Burke County is in order. An 
evaluation has been completed for lung carvxr in Burke 
County and no irxcreased occurrence was found. 

Cancer in Davie County — A request was swfcmitted 
to the Environmental Epidemiology Section in J 986 for a 
study of suspected higher-than-expected cancer rates in 
Davie County. Residents u^ere particularly concerned 
about hazardous emissions from irxdustries near the town 
of Cooleemee. The community organized a survey to 
identify additiorml cases; organizatUmal efforts were so 
successful that a unit of the American Cancer Society was 
formed from that beginning. Hou^ever, the conclusion 
from this study was that there was no evidence of 
increased carxcer rates. 

Using the CLUSTER software, an arxalysis of the 
cancer experience in Davie Courxiy was re-evaluated arxd 
extended through 1 988. Over the J 984-88 period, Davie 
County's liver and bladder cancer death rates were 
elevated above the state rates; however these excesses were 
based on very srruxll nurrxbers (i.e., averages oforxe death 
or less per year) and therefore are not considered reliable 
estimates. The Davie County lung, leukemia, kidrxey and 
brain cancer death rates were lower than the state's. 

Myelogenous Leukemia in "North Carolirui — 

The Environmental Epidemiology Section requested an 
arwdysis of 1984-88 age-adjxisted mortality rates of 
myelogerxous leukemia. Their objective was a search for 
potential clusters associated with point sources ofairborrxe 
emissions ofbenzerxe. A visiml irxspection of a map with 
the myelogerxous leukemia rates wets performed at the tinxe 
of the initial request. Now a statistical arxalysis for 
evidence of clustering is available using the CLUSTER 
software (see Figure 3). 



Twenty-six counties had very high myelogenous leukemia 
mortality rates (> 3.4/100,000); some of these rates in 
extreme eastern and western counties may he urxstable due 
to the very small numbers oj cases involved. The state ar\d 
ruitioruxl rates of myelogenous leukemia mortality were 
2.5/100,000. Rates for forty-four counties were 
significantlyhigher (i.e., ^ 2.7/ 100,000). The distribution 
of these counties with significantly elevated rates provides 
evidence of several clusters that may offer leads for further 
investigation (probability of observed clusters p < 0.001; 
p < 0.05 for counties with very high rates). A special 
study of leukemia occurrence in the central Piedmont 
counties is already under way. 

DISCUSSION 

Many public health experts believe that evaluating 
cancer cluster reports is a valuable service. The new 
protocol developed for evaluating cancer cluster 
reports has greatly increased the responsiveness to 
citizen concerns, e.g., twenty-seven cluster reports 
were "closed" using the new protocol in the 
comparable time that one report (Rowan County) 
was evaluated using former procedures. The new 
protocol already provides greater cost-effectiveness 
and timeliness in handling cancer cluster reports 
through the use of statistical analyses of the available 
data in place of the costly process of collecting new 
data for each cluster. As the new protocol is refined, 
it will provide a systematic approach to cancer 
cluster investigation and analysis; this will mean a 
straightforward, step-by-step process that can be 
explained to persons reporting clusters. 

Also, much greater contact is being made with 
local residents to provide educational programs 
(nine on-site lectures were provided as a part of the 
twenty-seven "closed" cancer cluster evaluations). 
These community presentations help to assuage 
community concerns and extend a positive response 
to public inquiries. These educational programs 
provide answers to legitimate questions about both 
cancer prevalence and possible environmental 
associations. To facilitate these educational goals, an 
informational brochure was developed in collabora- 
tion with the American Cancer Society; it is available 
by request. In addition to the evaluations described 
in this report, the staff of the Cancer Surveillance 



Section have been involved in four consultations 
related to potential cancer clusters in North Carolina, 
one in each of Harnett, Robeson, Burke and Catawba 
counties. 

This greater effectiveness and visibility have led to 
reports of disease clusters other than cancer being 
referred to the Cancer Surveillance Section. Three 
such cluster reports are: 

A potential cluster of Multiple Sclerosis in 
Alleghany County. 

Two cases of a rare dermatologic condition 
diagnosed in neighbors in Cabarrus County. 

A series of spontaneous abortions, in a two- 
month period, among neighbors in Wake 
County. 

However, for so many cluster reports, even the 
time required for site visits and data analyses compels 
the Cancer Surveillance Section to do cluster 
evaluations as time permits and where travel makes 
site visits convenient. The work with cancer clusters 
will continue, although recent budget constraints 
will lengthen the time to complete evaluations. The 
twenty-seven reports described here as "closed" 
averaged three months for evaluation; this does not 
include the extensive Rowan study that required 14 
months for completion. Such rigorous and detailed 
efforts must be reserved for those clusters that truly 
warrant such intensity, including those identified 
through proactive cancer surveillance. 

CONCLUSION 

Cancer cluster investigations may represent a 
social service more than scientific research. Cluster 
investigations should not be viewed strictly for their 
scientific research merit, but also for their role as an 
important interactive public health activity. "The 
public is increasingly demanding answers regarding 
possible associations between [cancer] and the 
environment." (Fiore, et al., 1990). The evolving 
procedures described in this report address these 
concerns with a sound epidemiologic approach to 
responding to cancer cluster reports. 



REFERENCES 

Aldrich, T.E., Atkinson, D.A., Hines, A. and Smith, C.G. ( 1990), The Establishment of a Population-Based 
Cancer Registry for North Carolina, North Carolina Medical Journal, 5 1(2): 107-12. 

Caldwell, G.G. (1989) Time-Space Cancer Clusters, HealtK and Environment Digest, 3(5): 1-3. 

Fiore, B.J., Haranhan, L.P. and Anderson, H. A. (1990), State Health Department Response to Disease Cluster 
Reports: A Protocol for Investigation, American Journal of Epidemiology, 132:S14-S22. 

Grufferman, S., Wang, H.H., Delong, E.R., et al. (1982), Environmental Factors in the Etiology of 
Rhabdomyosarcoma in Childhood, J. Nat. Cancer Inst., 68 (1): 107-13. 

Morant2, R.A., Neuberger, J.S., Baker, L.H., et al. ( 1985), Epidemiologic Findings in a Brain-Tumor Cluster in 
Western Missouri, J. Neurosurgery, 62: 856-60. 

Rabotti, G.F., Grove, A.S., Sellars, R.L., and Anderson, W.R. (1966), Induction of Multiple Brain Tumors in 
Dogs by Rous Sarcoma Virus, Nature, 20:884-6. 

SEER (1990), Cancer Statistics Review 1973-87, Pub. Surveillance Program, National Cancer Institute, NIH 
Pub. No. 90-2789. 

Thacker, S. (1989), Time-Space Clusters: The Public Health Dilemma, HealtK and Environvxent Digest, 
3(5):4-5. 

Warner, S.S. and Aldrich, T.E. (1988), The Status of Cancer Cluster Investigations Undertaken by State 
Health Departments and the Development of A Standard Approach, J. American Public Health Assoc., 
78(3):306-7. 

Selected Bibliography for Additional Reading 

National Conference On Clustering of Health Events, American Journal of Epidemiology (1990), 132 (1) 
Supplement, Twenty-six papers. Available from the Journal office, 2007 E. Monument Street, Baltimore, MD 
21205 for $11.00. 

Guidelines for Investigating Clusters of Health Events, Morbidit^i and Mortality Weekl:y Report ( 1990), Vol. 39 
(RR-11), 23 pages, 35 references. Available from the Massachusetts Medical Society, C.S.P.O. Box 9120, 
Waltham, MA 02254-9120 for $3.00. 

Aldrich, T.E. (1990), CLUSTER: Software to Assist Investigations of Rare Health Events, Diskettes and 
User's Manual — Available from the Agency for Toxic Substances, Health Studies Division, MS-E31, 1600 
Clifton Road NE, Atlanta, GA 30333 (no price identified). 



RIPOAT OF 
POSSIBLE 
DISEASE 
CLUSTER 



PROXIPML DATA 
RCVIEV 




CONTACT WITH 
\ LOCAL ,. 
^ACEUCY NTT- 
f. 



REPORTING 



FILE ^ 
KAIHTAIHEMCE^ 



CONTINUED 
SURVEILLANCE 



PREVENTION 



/< 

DISCONTINUE 
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/ 



r^. 



NO EVIDENCE OF 
auSTERING 



ON-SITE J r 

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CON FOUNDERS 



I I 

I 
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STATISTICAL 
ANALYSIS 



RISK 
FACTi 



PROBABLE 
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. PRimRY 
-^ EVALUATION - 
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.DECISION POINT 



INCONCLUSIVE 
EVIDENCE OF 
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EHCNDCO 
EPIDEM10L06K 
STUDY 



/ 



EXTENSIVE 
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ASSESSMENT 



POSSIBLE 
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Figure 1 — North Carolina Protocol for Evaluating Cancer Cluster Reports 



10 



Cancer Cluster Reports 

Received By County 



September 1989 Through December 1990 




N.C. Cluster Reports 

no cluster reports received [H 

1 cluster report received Fl 

2-3 cluster reports received H 

4 or more reports ■ 



Figure 2 — Cancer Cluster Reports by County 9/1/89 to 12/31/90 



11 



Age- Race- Sex Adjusted Death Rates 
for Myelogenous Leukemia 

North Carolina, 1984-88 



Deaths per 100,000 
Population 

D 0.00 to 2.49 

D 2.50 to 2.69 

M 2.70 to 3.39 

■ 3.40 to 8.00 



(1970 U.S. standard) 




* Rates of 2.7 or greater were significant at .05 level 

Figure 3 — Map of Myelogenous Leukemia Mortality 1984-1988 
Age- Race- Sex-adjusted Rates (1970 U.S. standard) 



12 



Table 1 — North Carolina Cancer Cluster Reports Received 9/1/89 to 12/31/90 



County 

Alleghany 

Ashe 

Beaufort 

rWaufort 

Bertie 

Brunswick 

Burke 

Caldwell 

Catawba 

Catawba 
Chowan 
Cleveland 

Cumberland 

Davidson 

Forsyth 

Gaston 
Gaston 
Gaston 

Granville 
Guilford 
Guilford 

Johnston 

Mecklenburg 

Mecklenburg 



Mecklenburg 
Mecklenburg 
Mecklenburg 

New Hanover 
New Hanover 
Northampton 

Rockingham 
Rockingham 
Rowan 

Rutherford 

Stanly 

Stanly 

Surry 
Surry 
Surry 

Union 
Wake 
Wake 

Wake 
Wake 
Warren 

Washington 
Washington 
Wayne 

Wilson 



Description 

Possible excessive rates in small town 
Concern for excess cancer in the county* 
Suspected drinking water contamination 

Concern for excess cancers in local area 
Possible increased cancer among neighbors 
Brain cancer around nuclear power plant 

Fear of lung cancer due to plant emissions* 
Kidney cancer cases in small area 
Concern for cancers near industrial park 

Six neighborhood cancers in two years 
Concern for local paper plant emissiotis 
Multiple cases in one neighborhood* 

Eight cancer cases among 30 homes 
Concern for cancers near industrial park 
Four gastrointestinal cancers in neighborhood 

Three rare pediatric tumors in small town* 
Concern for cancers near industrial park 
Hodgkin's Disease in rural area 

Concern for increased lymphomas* 

Possible excess rates in Summerfield community 

Possible excess rates in Jamestown neighborhood 

Concern for increased cancer in neighborhood 
Concern for increased cancer in neighborhood 
Three leukemia cases in small area 



Concern for increased cancer in neighborhood* 

Concern for industrial emissions 

Six breast cancer cases in neighborhood 

Four colon cancer cases in neighborhood 

Concern for increased cancer in neighborhood 

Concern for increased brain cancer in county* 

Concern for increased cancer in neighborhood* 

Concern for increased cancer in neighborhood 

Concern for increased brain cancer in county 

Concern for increased cancer in neighborhood 

Concern for excess cancer in the county* 

Concern for excess cancer in the county 

Excess upper respiratory cancer suspected 

Concern for increased cancer in neighborhood 

Concern for increased cancer in neighborhood 

Concern for increased cancer in work place 

Concern for increased cancer in neighborhood 

Concern for increased cancer in neighborhood 

Concern for increased cancer in neighborhood 

Concern for increased cancer in neighborhood 

Concern for cancers in household 

Concern for colon cancer excess in community 

Concern for local paper plant emissions 

Concern for increased cancer in neighborhood 

Concern for increased cancer in neighborhood 



Status 

Pending 

Collecting data 

UNC — study in progress 

In active evaluation 
Closed — No increase found 
Closed — No increase found 

Closed — No increase found 
In active evaluation 
Closed — No increase found 

Closed — No increase found 
In active evaluation 
Pending 

Pending 

Closed — No increase found 

Closed — No increase found 

Real Cluster — see text 
Closed — Familial grouping 
Pending 

Real cluster — see text 
Closed by local Health Dept. 
Health Department following 

Closed — No increase found 
Closed — No increase found 
Closed — Cases occurred over a 
long time period 

Collecting data 

Closed — No increase found 

Collecting data 

Real cluster — see text 
Closed — No increase found 
Real cluster — see text 

Closed — No increase found 

Pending 

Real cluster — see text 

Pending 
Collecting data 
Collecting data 



Student project- 
Pending 
Pending 



closed 



Pending 

Closed — No increase found 

Closed — No increase found 

Closed — No increase found 

Pending 

Closed — Familial grouping 

Local M.D. following 
In active evaluation 
Closed — No increase found 

Pending 



'Educational program presented. 



13 



Table 2 — North Carolina Cluster Reports of Other Health Effects 
Received 9/1/89 to 12/31/90 

County Description Statiu 

Alleghany Multiple Sclerosis — multiple cases In active evaluation 

Cabarrus Lobular Panniculitis — Two young girls Searching for additional cases 

No suspected environmental factors 

Wake Three spontaneous abortions in close friends In active evaluation 



14 



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