ENVIRONMENTAL RESEARCH56, 131--143 (1991)
Epidemiologic Investigation of a Cancer Cluster in Professional Football Players ALLEN KRAtrr,* E V A
CHAN,'~ P A U L J.
LIov,$
FREDRICK B . C O H E N , §
BERNARD O . GOLDSTEIN,:~ AND PHILIP J. L A N D R I G A N t
*Departments of Internal Medicine and Community Health Sciences, University of Manitoba, NA--618 700 McDermot Avenue, Winnipeg, Canada R3E OW3; tDivision of Environmental and Occupational Medicine, Department of Community Medicine, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1057, New York, New York 10029; ~:Department of Environmental and Community Medicine and the Environmental and Occupational Health Sciences Institute, UMDNJ--Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854-5635; and §Department of Oncology, Beth Israel Medical Center, 201 Lyons Avenue, Newark, New Jersey 07112 Received June 19, 1991 In 1976, the New York Giants professional football team relocated to the newly constructed Meadowlands Sports Complex (MSC) in East Rutherford, NJ. Between 1980 and 1987 four team members developed cancer: one case each of non-Hodgkin's lymphoma, glioblastoma, angiosarcoma, and Hodgkin's disease. Because the surrounding area contains three superfund sites, concern was widespread that the cancers were related to environmental contamination. To assess for a possible environmental etiology, we conducted clinical, environmental, and epidemiologic studies at the MSC. Measurements of volatile organic compounds were all below occupational exposure limits and were similar to ambient levels in nearby Lyndhurst, NJ. Outdoor AM radio broadcast field strengths were in the uppermost 0.1% of field strengths measured in urban areas of the United States. Proportionate mortality ratio and proportional cancer incidence ratio studies of the MSC workforce found no excesses of cancer deaths or of incident cancer cases either for all sites combined or for any specific site. No significant differences in cancer incidence or mortality were found between indoor and nonindoor workers. Based on examination of all available data, the four cancer cases were judged most likely to have been clustered by chance and not to have been caused by environmental conditions at the MSC. © 1991 AcademicPress,Inc.
INTRODUCTION Cancer clusters, groups of cancer cases that occur together in place and time, pose a major dilemma in public health (Bender et al., 1990; Neutra, 1990). Clusters have in some instances provided the first warning of newly emerging problems in environmental carcinogenesis; examples have included mesothelioma in asbestos-exposed individuals (Wagner et al., 1960), angiosarcoma of the liver in vinyl chloride polymerization workers (Creech and Johnston, 1974), and lung cancer in chemical workers producing bis-chloromethyl ether (Figueroa et al., 1973). Many other reported clusters have, however, had no discernible common etiology or have been shown on further study to contain no more cancer cases than would be expected in the general population (Greenberg et al., 1985). Cancer clusters require evaluation. They must be studied in sufficient detail to permit identification of those with a common etiology and thus to distinguish true clusters from statistically random events. Evaluation must additionally be con131 0013-9351/91 $3.00 Copyright© 1991by AcademicPress, Inc. All rightsof reproductionin any formreserved.
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ducted in an open manner. Only through open evaluation can legitimate public concerns about clusters be addressed, concerns that may be especially intense when a cluster is reported to occur in a highly visible group or in an environment that is perceived to be contaminated. Yet evaluation must also be efficient, costeffective, and prompt. In this report we describe the evaluation of a cancer cluster in a highly visible group, a professional football team, in a location that is perceived to be highly polluted. We also outline an approach to the systematic assessment of common environmental etiology in cancer clusters.
BACKGROUND In 1976, the New York Giants professional football team relocated from New York City to the newly constructed Meadowlands Sports Complex (MSC) in East Rutherford, NJ. Between 1980 and 1987 four members of the football club developed cancer. The cancers were non-Hodgkin's lymphoma, glioblastoma, angiosarcoma, and Hodgkin's disease. Two were eventually fatal. The MSC was built in the marshland of northern New Jersey over a cleared refuse disposal site and is still surrounded by three EPA Superfund toxic waste sites known to contain mercury, waste oil, and organic wastes. As northern New Jersey is known to have cancer rates higher than the U.S. average (Prickle et al., 1987), concern arose both in the news media and the community that these cases of cancer in the professional football players might in some way be related to environmental factors present at the complex. This perception was reinforced by the fact that no cause had been identified for a cluster of childhood leukemia and Hodgkin's disease cases which had been reported a few years earlier in the nearby town of Rutherford, New Jersey (Halperin et al., 1980). There was speculation that the clusters may have been related to a common environmental etiology. Following the widely published diagnosis of the fourth cancer case in a football player in September 1987 the New Jersey Sports and Exposition Authority (NJSEA), managers of the complex, convened a medical committee to investigate whether environmental conditions present at the MSC might have played a role in the development of cancer in the four football players. A three-part plan--clinical, environmental, and epidemiologic--was developed. The first phase, an evaluation of the medical records of the four football players, confirmed all of the diagnoses. Additionally it established that the cancers were diagnosed six, four, one, and four years respectively after the players began working at the sports complex (Table 1). No common clinical factors were identified.
ENVIRONMENTAL ASSESSMENT The environmental assessment consisted of: 1. Review of all available data on air measurements for potentially toxic materials for the site and the surrounding areas. These data were limited since air contaminants were not routinely sampled at and around the MSC. 2. Direct measurements of volatile organic compounds (VOC) during the sum-
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CANCER CLUSTER IN FOOTBALL PLAYERS TABLE1 POSITIONS AND DEMOGRAPHICS OF THE FOOTBALL PLAYERS DIAGNOSED WITH CANCER
Position
Age at diagnosis
Race
Cancer type
Year joined team
Year of diagnosis
Linebacker Running back Running back Lineman
26 31 23 27
White White White While
Lymphoma Gfioblastoma Angiosarcoma Hodgkin's disease
1976 1976 1983 1983
1980 1982 1984 1987
mertime to characterize any local increase due to soil outgassing during a time of the year when any soil emissions would be the highest. The sampling was important since the cases reported had been through the period 1980-1987 and if soil emissions were related to the occurrence of the cancer cases would still be representative. 3. Direct measurements of electric field strengths at sites within and surrounding the complex since three AM radio station towers are located at the MSC and five more are within 2-3 miles. These measurements were also necessary since the towers had been operational throughout the 1980-1987 period. For the second component of the environmental assessment the VOC samples were collected at three locations: the practice field, a natural grass field outside Giant Stadium, Giant stadium, and the race track as noted on Fig. 1. These sites were selected for two reasons: (1) the practice field and the stadium are the locations where the football players spent the greatest proportion of their time outdoors, and (2) the racetrack is a location where many outdoor MSC employees spend their workday exposed to the soil throughout the year. Sampling occurred during June-July 1988, a period coinciding with a major heat wave, which would act to enhance any local soil emissions. Samples were collected every third day at each location for an 8- to 9-hr period during daylight hours. They were collected on different types of Supelco carbotraps (S-III for vinyl chloride, C for heavy compounds) and the samples were analyzed on a Varic-3700 gas chromatograph. Analysis error ranged from 12 to 19% depending upon the compound. Mass spectral (Hewlett-Packard) verification was done on 15% of the samples. Air measurements for VOC had been made previously in the locker and weight rooms (NIOSH, 1987); no significant levels were recorded. Electric fields were measured with an electrical field strength meter (Instruments for Industry, S/N 12705-F) at randomized locations within the MSC and adjacent areas (Tell and Van Pelt, 1988). Measurements were taken inside and outside buildings, in parking lots, and near the New Jersey Turnpike. The average VOC concentrations found at each site are listed in Table 2 along with data previously collected at Lyndhurst, N J, a residential community approximately 3 miles from the MSC (Roytvarf, 1988). All data collected at the MSC were well below OSHA permissible exposure limits (United States Code of Federal Regulations Title 29, 1989) for employees at the site, and not significantly different from ambient values obtained in adjacent residential neighborhoods in Lyndhurst, NJ.
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/
FIG. 1. Meadowlands Sports Complex site plan. (X) denotes location of VOC sampling.
Results of the electric field measurements revealed that outdoor AM radio broadcast field strengths at the MSC were in the uppermost 0.1% of field strengths measured in urban areas of the United States (Tell and Van Pelt, 1988). The root summed square (RSS) for all AM calling signals ranged from 0.013 to 9.63 V/m. The football players' locker room had a RSS of 0.0107 V/m. All indoor measurements were lower than those recorded outdoors. Further, electric field levels in the stadium were lower than those found in the stadium parking lot and along the New Jersey turnpike. In all cases these levels were lower than standards specifying human occupational exposures. Review of water drainage patterns found no indication that ground water from nearby toxic waste sites had contaminated soil within the sports complex. Soil within the complex consisted of fill brought from other locations, and this imported soil was separated from the marshlands by a cofferdam.
EPIDEMIOLOGIC ASSESSMENT The third phase of the investigation, an epidemiologic assessment, was undertaken to determine whether the pattern of deaths or of incident cancer cases
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CANCER CLUSTER IN FOOTBALL PLAYERS
TABLE 2 AVERAGE CONCENTRATIONS OF VOC MEASURED AT THE MEADOWLANDS SPORTS COMPLEX AND 1N LYNDHURST, NJ Compounds (ppb)
PF
RT
GS
LND
Vinyl chloride Dichloromethane Ethylene chloride 2-Butanone Tetrahydrofuran 1,1,1-Trichloroethane Benzene Trichloroethylene Methylcyclohexane Toluene Tetrachloroethylene Ethylbenzene p- and rn-Xylene o-Xylene Trimethylbenzene Naphthalene
1.7 1.4 0.9 0.4 0.3 0.6 0.3 1.1 0.1 2.0 1.3 0.2 10.1 0.4 0.1 0.0
0.9 2.1 0.5 0.4 0.2 0.8 0.2 1.5 0.1 2.9 1.3 0.3 3.3 0.3 0. I 0.0
2.1 1.2 0.8 0.3 0.2 0.5 0.2 0.9 0.1 1.1 1.8 0.1 5.7 0.2 0.1 0.0
-1.9 0.8 1.0 0.3 0.8 0.2 1.6 0.4 2.5 0.9 0.3 4.1 0.2 0.1 0.0
Note. PF, practice field; RT, racetrack; GS, Giant Stadium; LND, Lyndhurst.
among the entire MSC workforce was different from that expected in New Jersey. Data were obtained on all cases of cancer in the workforce, but the cancer diagnoses of greatest concern were those developed in the football players and of leukemia. Leukemia was specifically investigated because a relationship between chronic exposure to electromagnetic fields and leukemia, although not conclusively established, has been suggested by epidemiologic studies (Wertheimer and Leeper, 1979; Milham, 1985; Ahlbom, 1988). METHODS Each of the 15 union and 8 employer groups represented at the complex was contacted and asked to provide lists of all their members or employees who had worked at the complex since it opened, along with their birth dates, social security numbers (SSN), date of hire, and duration of employment. Lists of cancer cases and of known deaths among these workers were also requested. The NJSEA provided a complete list of its payroll records. As a large number of these workers were part time or temporary, only workers who had worked at least 1 day in 2 calendar years were included in the study; 5787 MSC employees met these criteria. The Giants Football Club and one of the firms that managed security at the complex provided employment information on 957 and 1145 workers, respectfully. Two union groups provided demographic data on their membership totalling 458 individuals. A third union supplied morbidity and mortality information. Other employers and unions could not provide any of the requested information. In total 7889 individuals were included in the epidemiologic investigation. Birthdates were available for 2785 of these persons, and sex and race information was
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available for 1213 and 822 individuals, respectively. For approximately 90% of the cohort the last recorded address was in New Jersey. Due to the incomplete demographic information available for the cohort, proportionate mortality ratio (PMR) and proportional cancer incidence ratio (PCIR) studies were performed. Three sources were used to identify deaths among the cohort: the Social Security Administration (SSA), the National Death Index (NDI), and employer and union records. Individuals not identified as dead by any of these sources were presumed to be alive. In total, 235 deaths were identified in the cohort as having occurred between January 1, 1978 and December 31, 1987. A total of 228 death certificates, 97.0% of those sought, were obtained. To exclude individuals whose cancer diagnosis predated employment at the MSC, the date of diagnosis was obtained from information supplied by the New Jersey State Cancer Registry for those individuals who died in New Jersey with cancer. Four individuals who had developed cancer prior to September 1976 were removed from the analysis. One previously unidentiffed cancer death was discovered by the registry and was included in the PMR study. A total of 225 deaths were analyzed. Detailed analysis comparing the cost and utility of the various sources of decedent information is presented elsewhere (Kraut et al., in preparation). Death certificates were referred to a nosologist for standardized coding of cause of death. The PMR study was then performed using the PMR.BAS computer program (Maizlish, 1988). This program used United States death ratios in calculation of PMR rates. As 90% of the deaths occurred in New Jersey, computer tapes listing race- and sex-specific New Jersey deaths stratified by 5-year age intervals for the years 1977-1985 were purchased from MPDS (Mortality and Population Data System, University of Pittsburgh). New Jersey death ratios were computed for these years and converted into the PMR.BAS input format allowing for New Jersey-specific comparisons. Mortality ratios for 1986 and 1987 are extrapolated in linear fashion from 1985 rates. RESULTS: PMR STUDY Initial analysis was performed using US death ratios, but as these results did not differ significantly from those obtained using New Jersey deaths ratios, only the latter are presented. The MPDS data allowed calculation of New Jersey-specific mortality ratios for 32 causes of cancer death and 18 other conditions. Of the 225 deaths identified, 187 were in white males, 21 in nonwhite males, 13 in white females, and 4 in nonwhite females. Table 3 lists PMR data for white males alone and for all sex and race groups combined. Non-Hodgkin's lymphomas are classified with other lymphocytic diseases. In total 65 cancer deaths were observed (PMR 1.07; 95% CI 0.83-1.37). Nonstatistically significant elevated PMRs based on one, two, and one case were present for bone and bladder carcinoma and Hodgkin's disease, respectively. However, no overall or site-specific increased proportionate cancer mortality was observed in the MSC workforce. Specific attention was placed on identifying deaths from the types of cancer diagnosed in the football players and leukemia. The only death from a brain
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CANCER CLUSTER IN FOOTBALL PLAYERS TABLE3 PROPORTIONATE MORTALITY RATIOSIN THE MSC WORKFORCE, 197~I987
White males a Obs All malignant neoplasms Cancer of digestive organs and peritoneum Cancer of lung Cancer of brain and other CNS sites Lymphosarcoma and reticulosarcoma Hodgkin's Disease Leukemia and aleukemia Cancer of other lymphatic tissue All lymphopoietic cancer Cirrhosis of liver All nonmalignant causes of death a
Exp
Obs/exp
50
49.80
1.00
11 22
13.20 17.28
1
All sex/race groups combined ~ 95% CI
Obs
Exp
Obs/exp
0.75-1.32
65
60.60
1.07
0.83-1.37
0.83 1.27
0.42-1.49 0.80-1.93
14 25
15.64 20.08
0.90 1.25
0.49-1.50 0.81-1.84
1,65
0.61
0.06--3.40
1
1.89
0,53
0.01-2.94
1 0 0
0.66 0.48 1.96
1.51 0.00 0.00
0.15-8.47 XXXX-3.44 XXXX-1.87
1 1 0
0.79 0.59 2.22
1,27 1.69 0.00
0
1.87
0.00
XXXX-1.96
2
2.21
0.90
0.10-3.27
1 13
4.97 6.33
1.71 2.05
0.02-1.73 1.0%3.51
4 13
5.81 7.40
0.69 1.75
0.1%1.76 0.94-3.00
137
137.20
1.00
0.84-1.18
0.97
0.83-1.14
160 164.40
95% CI
0,02-7.04 0.02-9.43 XXXX-1.65
N e w Jersey-specific mortality ratios are used in these comparisons.
neoplasm was in the football player already known to have this condition. N o additional deaths were coded to angiosarcoma. One white male died of lymphosarcoma. One white woman died of Hodgkin's disease and another of nonHodgkin's lymphoma. The only death certificate listing leukemia was for a nonwhite male who began working at the complex in 1977 and was diagnosed with multiple myeloma in 1978. This individual died of plasma cell leukemia in 1981. The nosologist coded the death to multiple myeloma. To assess the effect of latency, mortality ratios were compared for individuals dying less than and more than 5 years from the beginning of their employment at the complex. If environmental exposures at the stadium had contributed to the football players' cancer deaths, it is likely that a stronger effect would be seen in the group who had died more than 5 years after the start of employment. A total of 109 workers died within 5 years from their date of hire at the MSC, while 116 died more than 5 years after this date. The all malignancy PMR was 1.09 (95% CI 0.74-1.56) in the group dying less than 5 years and 1.06 (95% CI 0.74-1.47) in the group more than 5 years from date of hire. Thus, no trend with increasing latency was observed. Analysis of latency periods for the five diagnoses of particular concern--nonHodgkin's lymphoma, leukemia, Hodgkin's disease, brain tumors, and angiosarcoma--showed that only the brain cancer, diagnosed in the football player, and a case of Hodgkin's disease had occurred in workers more than 5 years after their initial date of hire at the MSC. To assess whether outdoor jobs, i.e., those with potentially increased environ-
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KRAUT ET AL.
mental exposure (e.g., VOC or electromagnetic fields), were associated with increased cancer mortality, all jobs were classified by knowledgeable management personnel as either indoor, mixed, or outdoor. Classification was performed without knowledge of the job titles of deceased workers. All workers having mixed or outdoor jobs were termed to have nonindoor employment. In total, 72 deceased individuals, 62 white males, 9 nonwhite males, and 1 white female were classified as having nonindoor jobs. The female died of atherosclerotic heart disease. In this group 19 cancer deaths were observed versus 19.47 expected (PMR 0.98; 95% CI 0.5%1.52). The PMR for all malignancies for indoor workers was 1.12 (95% CI 0.82-1.49) based on 153 observed cases. Nonindoor workers did not die proportionately more frequently of cancer than indoor workers. Other than the two cancers detected in the deceased football players, no other deaths due to the diagnoses of concern were identified in nonindoor workers.
METHODS: PROPORTIONATE CANCER INCIDENCE RATIO STUDY Four sources were used to identify incident cancer cases: the New Jersey State Cancer Registry, death certificate review, employer and union records, and a questionnaire sent to all current employees asking whether they had ever been diagnosed as having cancer of any sort. Those answering yes were asked to sign a medical release form so that the diagnosis could be confirmed. Only individuals whose medical records contained a histological report confirming cancer were included in the analysis. A computer tape listing all cohort members was submitted for linkage to the New Jersey State Cancer Registry. Registry records are reportedly complete for the years 1979 through 1985. Partial listings are available for 1986 and 1987. New Jersey residents diagnosed with cancer in New York State, Pennsylvania, and Delaware are reported to the registry. A total of 132 individuals were reported as having cancer by the New Jersey State Cancer Registry after beginning employment at the MSC. An additional five individuals were found to have had cancer diagnosed prior to first employment at the complex and were not included in the study. The 82 deaths identified from the PMR study and all death certificates available for 1988 reporting cancer as either the cause of death or as a coexisting condition were included in this phase of the study. The date of cancer diagnosis was obtained from the New Jersey cancer registry in 45 cases. In 25 of the remaining cancer cases, date of diagnosis was approximated from the duration of cancer reported on the death certificate. For the remaining 12 cases, date of cancer diagnosis was approximated utilizing the clinical experience of the investigators and a recognized oncology source (De Vita et al., 1985). Date of diagnosis was presumed to be 6 months prior to death for four metastatic carcinomas of unknown origin, 1 year prior to death for seven lung cancers and for a case of "brain tumor" without histologic verification, and 2 years for one case of carcinoma of the floor of the mouth. In four deceased individuals cancer was diagnosed prior to beginning employment at the MSC; these workers were not included in the anal-
C A N C E R C L U S T E R IN F O O T B A L L P L A Y E R S
139
ysis. Thirty-seven cancer cases were identified from employer, union records, and the questionnaire. The termination date for the PCIR study was set at December 31, 1987 even though it is possible that some cancer cases were not identified for the years 1986 and 1987. This date was chosen instead of December 31, 1985, the final date for which the New Jersey cancer registry had near complete information, because it allowed for analysis of an additional 49 cases of cancer, 50% of the previous total, and added 2 years or 25% to the potential latency period. In addition one of the football players with cancer would not have been included in the study if the termination date had been set at December 31, 1985. In total, 146 individuals were identified to have developed cancer following employment at the MSC between January 1, 1978 and December 31, 1987. One person had two different cancers diagnosed and is treated in the analysis as two separate individuals giving a total of 147 cancers for analysis in the PCIR. Proportionate cancer incidence ratio data for New Jersey was obtained using a computer program developed by the New Jersey Department of Health (Hall and Livright, 1988). This program identifies 32 different cancer sites and using information obtained from the New Jersey State Cancer Registry calculates age, race, and New Jersey-specific cancer incidence for the years 1979-1984. Linear extrapolation of these data was performed for the years 1978 and 1985-1987. For white males both general population and blue collar rates are available. In this program angiosarcomas are classified with soft tissue tumors. Using the method of Rothman and Boyce (1983), 95% confidence intervals were calculated. RESULTS: PCIR STUDY Of the 147 cancer cases, 108 occurred in white males, 26 in white females, 8 in nonwhite males, and 5 in nonwhite females. As 73.5% of the cancer cases occurred in white males, the strongest inferences regarding cancer morbidity can be made regarding this group. No statistically significant excesses in cancer morbidity were observed at any anatomical site. Elevated PCIRs were seen for nasopharyngeal cancer and carcinoma of the breast in males, but these findings were based on only one observed case. Nonstatistically significant excesses of cancers of the oral cavity and pharynx were also found. A statistically significant decrease in the proportion of stomach cancers was observed. This finding is likely due to the overestimation of the expected values due to decreasing stomach cancer incidence rates (Maizlish, 1988). The small number of cases of cancer at specific sites in nonwhite males and in white and nonwhite females make analyses of these data difficult to interpret. Thus to utilize the information provided by these age and sex groups, overall cancer morbidity ratios were calculated combining all race and sex groups. Blue collar white male ratios were used for comparison in this analysis (Table 4). No statistically significant excesses were observed for Hodgkin's disease, nonHodgkin's lymphoma, soft tissue tumors, brain tumors, or leukemia. No additional cases of angiosarcoma were found. No unusual grouping of job titles were
140
K R A U T ET A L . TABLE 4 PROPORTIONATE CANCER MORBIDITY RATIOS IN THE M S C WORKFORCE, 1978-1987
White males
All cancers Oral cav. and pharnyx All digestive Stomach Trachea and lung Soft tissue Brain All lymphocytic Hodgkin's Non-Hodgkins Lymphoma All leukemias
Obs
Exp ~
108
108
Obs/exp
All sex/race groups combined 95% CI
Obs
Exp ~
147
147
Obs/exp
95% CI
7 21 0 30 2 1 8 4
3.78 24.61 3.19 27.61 0.94 1.77 6.43 2.81
1.85 0.85 0.00 1.09 2.14 0.57 1.24 1.42
0.74-4.40 0.53-t.27 XXXX-0.68 0.73-1.57 0.24-9.04 0.01-2.80 0.54--2.57 0.38-3.96
8 26 0 36 2 1 11 5
5.00 30.78 3.84 32.43 1.24 2.35 8.20 3.58
1.60 0.84 0.00 1.11 1.62 0.43 1.34 1.40
0.69-3.15 0.55-1.24 XXXX-0.96 0.78-1.54 0.18-5.85 0.01-2.37 0.67-2.40 0.45-3.26
4 1
3.62 2.86
1.10 0.35
0.30-2.90 0.00-1.55
6 2
4.63 3.57
1.30 0.56
0.47-2.82 0.06-2.02
Blue collar white male control ratios are used in calculating the expected valves.
found either for all cancer cases together or for individual diseases examined separately. Special attention was placed on examination of the cancer morbidity and mortality pattern of the Giants employees. Other than the four cases in the football players, two other cancer were identified in this group, both in office personnel. One man reported to have died of atherosclerotic heart disease had renal carcinoma concomitantly. The other died of lung cancer. Analysis was also performed of the incidence of cancers occurring more and less than 5 years from date of first hire at the MSC. In 82 cases cancer was diagnosed within 5 years of the date of hire, while in 65 cases the diagnosis was made more than 5 years after onset of employment. No significant excesses were observed for any of the diagnoses of concern when examination by latency was undertaken. Cancer morbidity ratios were quite similar for all of these diagnoses in both groups. A further analysis was performed comparing cancer incidence in the 101 indoor workers with the 46 nonindoor workers, Eight nonindoor workers had nonHodgkin's lymphoma, Hodgkin's disease, soft tissue cancers, or brain tumors. Four of these were the originally identified football players. Of the other four, three had non-Hodgkin's lymphoma, and one had Hodgkin's disease. The three cases of non-Hodgkin's lymphoma were observed in a parking toll collector, a security guard, and an operating engineer. Both cases of leukemia occurred in indoor workers. A nonstatistically significant increase in the PCIR for non-Hodgkin's lymphoma (2.33; 95% CI 0.63-5.97) was seen in nonindoor workers. This finding should be interpreted in conjunction with the fact that an overall excess in non-Hodgkin's lymphoma was not observed in the study population as a nonstatistically signifi-
CANCER CLUSTER 1N FOOTBALLPLAYERS
141
cant decrease in the PCIR for this disease was seen in indoor workers (PCIR 0.69 95% CI 0.08--2.49).
DISCUSSION The negative results of the epidemiologic investigation are supported by the environmental measurements, which did not indicate any values above occupational guidelines or above typical urban levels in this area. The epidemiologic analysis, however, has a number of limitations. The first limitation is its low statistical power, or low ability to detect a significant excess of cancer cases if such an excess did actually exist. The low power of the study is due to the small number of expected cases with the cancer diagnoses of concern. Although 7889 individuals were entered into the cohort, based on the number of cancer cases observed only about 15 persons would have been expected to have had any of the diagnoses under study. The power of this investigation would be increased by reanalysis in the future when more cancer cases would have been expected to occur in the study population. A second limitation is that SSN were relied on heavily as the criteria for identifying deceased individuals. However, in certain cases a spouse or other family member may have also used the same number leading to misclassification. Although three such instances were detected, had we further identifying information more may have been discovered. A further limitation is that individuals who moved out of New Jersey and then developed nonfatal cancer would not have been identified by the state's cancer registry as having had cancer. It is highly unlikely, however, that a disproportionate number of the cancers of concern would self-select and move away from New Jersey. Therefore, this limitation does not appear to be major. The epidemiologic analyses presented in this report can be used only to estimate the past and current risk of cancer associated with employment at the MSC. Due to the long latency period of various forms of cancer, estimations of future cancer risk at the complex cannot be made from these data. However, if environmental conditions present at the sports complex led to the cancers reported in the football players, it is reasonable to suspect that other workers would have shown a similar excess cancer morbidity. Such an excess was not seen.
CONCLUSIONS An overall increase in cancer mortality was not observed in this study of employees of the Meadowlands Sports Complex. No increases in the proportion of cases of or deaths from leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, brain tumors, or angiosarcoma were found in the overall study population. No statistically significant excesses of cancer morbidity or mortality were observed for any specific type of cancer. In our opinion, based on the available clinical, environmental, and epidemiologic data, the four cases of cancer diagnosed in the professional football players were most likely related to chance and not to environmental conditions present at the MSC.
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KRAUT ET AL.
The three-phase evaluation--clinical, environmental, and epidemiologic-undertaken in this study proved useful in addressing the concerns of the workforce and management of the MSC as well as those of the citizens of the nearby communities. The strengths of our approach were that all potentially concerned groups were contacted and asked to participate, all available data and pertinent databases were utilized, and a structured systematic plan was outlined both prior to initiation and following through to completion of the investigation. The approach outlined in this report may thus serve as a model for other investigators studying similarly highly visible cancer clusters.
ACKNOWLEDGMENTS The authors acknowledge the assistance of the administration, staff, and unions working at the MSC in conducting this study. Also the help of W. Tell, PhD., W. Van Pelt, PhD., and Mr. B. Roytvarf in performing the environmentalsampling and D. Micheals, PhD., and N. Hall, PhD. in assisting with the epidemiologic analysis were most appreciated.
REFERENCES Ahlbom, A. (1988). A review of the epidemiologic literature on magnetic fields and cancer. Scand. J. Work Environ. Health 14, 337-343. Bender, A. P., Williams, A. N., Johnson, R. A., et al. (1990). Appropriate public health responses to clusters: The art of being responsibly responsive. Am. J. Epidemiol. 132, $48-$52. Creech, J. C., and Johnston, M. N. (1974). Angiosarcoma of the liver in the manufacture of polyvinyl chloride. J. Occup. Med. 16, 150-151. De Vita, V. T., Hellman, S., and Rosenberg, S. A. 0985). "Cancer: Principals and Practice of Oncology," 2nd ed., Lippincott, Philadelphia. Figueroa, W. G., Raszkowsky, R., and Weiss, W. (1973). Lung cancer in chloromethyl methyl ether workers. N. Engl. J. Med. 288, 1096-1097. Greenberg, R., Rosner, B., Hennekene, C., et al. (1985). An investigation of bias in a study of nuclear shipyard workers. Am. J. Epiderniol. 121, 301-308. Hall, N., and Livright, T. (1988). "Proportionate Cancer Incidence for New Jersey." New Jersey Department of Health. Halperin, W., Altman, R., Stemhagen, A., et al. (1980). Epidemiologic investigation of clusters of leukemia and Hodgkin's disease in Rutherford, New Jersey. J. Med. Soc. NJ 77(4), 267-273. Kraut, A., Chan, E., and Landrigan, P. J. (In preparation). Comparison of cost of searching for deaths: NDI vs SSA. Maizlish, N. A. (1988). "PMR.BAS: An interactive microcomputer program for standardized proportional mortality analyses." National Farm Workers Health Group, Berkeley, CA. Milham, S., Jr. (1985). Mortality in workers exposed to electromagnetic fields. Environ. Health Persp. 62, 297-300. Neutra, R. R. (1990). Counterpoint from a cluster buster. Am. J. Epidemiol. 132, 1-8. NIOSH (1987). Personal communication, Morgantown, WV. Prickle, L. W., Mason, T. J., Howard, N., et al. (1987). "Atlas of US Cancer Mortality among Whites: 1950-1980." DHHS Publication (NIH) 8%2900. US Government Printing Office, Washington, DC. Rothman, K. J., and Boyce, J. D. (1983). "Exact Testing and Estimation for a Poison Variate (Byar Approximation). Epidemiologic Analysis with a Programmable Calculator." USDHEW (NIH) Publ. No. 79-1649. US Government Printing Office, Washington, DC. Roytvarf, B. (1988). "Ambient Air Analysis for Volatile Organic Compounds in Three Locations in the Meadowlands Sports Complex, East Rutherford, NJ." Hackensack Meadowlands Laboratory. Tell, W., and Van Pelt, W. (1988). "An Investigation of Radiofrequency Field Strengths in the Vicinity
CANCER CLUSTER IN FOOTBALL PLAYERS
143
of the Meadowlands Sports Complex, East Rutherford, NJ., July 14-18." Tell Associates, Las Vegas, NV. United States Code of Federal Regulations Title 29, Part 1910. 1000 (1989). "Air Contaminants-Permissible Exposure Limits." US Department of Labor, Occupational Safety and Health Administration, US Government Printing Office, Washington, DC. Wagner, J. C., Steggs, C. A., and Marchand, P. (1960). Pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br. J. Ind. Med. 17, 260-271. Wertheimer, N., and Leeper, E. (1979). Electrical wiring configurations and childhood cancer. Am. J. Epidemiol. 109, 723-284.
Epidemiologic Investigation of a Cancer Cluster in Professional Football Players ALLEN KRAtrr,* E V A
CHAN,'~ P A U L J.
LIov,$
FREDRICK B . C O H E N , §
BERNARD O . GOLDSTEIN,:~ AND PHILIP J. L A N D R I G A N t
*Departments of Internal Medicine and Community Health Sciences, University of Manitoba, NA--618 700 McDermot Avenue, Winnipeg, Canada R3E OW3; tDivision of Environmental and Occupational Medicine, Department of Community Medicine, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1057, New York, New York 10029; ~:Department of Environmental and Community Medicine and the Environmental and Occupational Health Sciences Institute, UMDNJ--Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854-5635; and §Department of Oncology, Beth Israel Medical Center, 201 Lyons Avenue, Newark, New Jersey 07112 Received June 19, 1991 In 1976, the New York Giants professional football team relocated to the newly constructed Meadowlands Sports Complex (MSC) in East Rutherford, NJ. Between 1980 and 1987 four team members developed cancer: one case each of non-Hodgkin's lymphoma, glioblastoma, angiosarcoma, and Hodgkin's disease. Because the surrounding area contains three superfund sites, concern was widespread that the cancers were related to environmental contamination. To assess for a possible environmental etiology, we conducted clinical, environmental, and epidemiologic studies at the MSC. Measurements of volatile organic compounds were all below occupational exposure limits and were similar to ambient levels in nearby Lyndhurst, NJ. Outdoor AM radio broadcast field strengths were in the uppermost 0.1% of field strengths measured in urban areas of the United States. Proportionate mortality ratio and proportional cancer incidence ratio studies of the MSC workforce found no excesses of cancer deaths or of incident cancer cases either for all sites combined or for any specific site. No significant differences in cancer incidence or mortality were found between indoor and nonindoor workers. Based on examination of all available data, the four cancer cases were judged most likely to have been clustered by chance and not to have been caused by environmental conditions at the MSC. © 1991 AcademicPress,Inc.
INTRODUCTION Cancer clusters, groups of cancer cases that occur together in place and time, pose a major dilemma in public health (Bender et al., 1990; Neutra, 1990). Clusters have in some instances provided the first warning of newly emerging problems in environmental carcinogenesis; examples have included mesothelioma in asbestos-exposed individuals (Wagner et al., 1960), angiosarcoma of the liver in vinyl chloride polymerization workers (Creech and Johnston, 1974), and lung cancer in chemical workers producing bis-chloromethyl ether (Figueroa et al., 1973). Many other reported clusters have, however, had no discernible common etiology or have been shown on further study to contain no more cancer cases than would be expected in the general population (Greenberg et al., 1985). Cancer clusters require evaluation. They must be studied in sufficient detail to permit identification of those with a common etiology and thus to distinguish true clusters from statistically random events. Evaluation must additionally be con131 0013-9351/91 $3.00 Copyright© 1991by AcademicPress, Inc. All rightsof reproductionin any formreserved.
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ducted in an open manner. Only through open evaluation can legitimate public concerns about clusters be addressed, concerns that may be especially intense when a cluster is reported to occur in a highly visible group or in an environment that is perceived to be contaminated. Yet evaluation must also be efficient, costeffective, and prompt. In this report we describe the evaluation of a cancer cluster in a highly visible group, a professional football team, in a location that is perceived to be highly polluted. We also outline an approach to the systematic assessment of common environmental etiology in cancer clusters.
BACKGROUND In 1976, the New York Giants professional football team relocated from New York City to the newly constructed Meadowlands Sports Complex (MSC) in East Rutherford, NJ. Between 1980 and 1987 four members of the football club developed cancer. The cancers were non-Hodgkin's lymphoma, glioblastoma, angiosarcoma, and Hodgkin's disease. Two were eventually fatal. The MSC was built in the marshland of northern New Jersey over a cleared refuse disposal site and is still surrounded by three EPA Superfund toxic waste sites known to contain mercury, waste oil, and organic wastes. As northern New Jersey is known to have cancer rates higher than the U.S. average (Prickle et al., 1987), concern arose both in the news media and the community that these cases of cancer in the professional football players might in some way be related to environmental factors present at the complex. This perception was reinforced by the fact that no cause had been identified for a cluster of childhood leukemia and Hodgkin's disease cases which had been reported a few years earlier in the nearby town of Rutherford, New Jersey (Halperin et al., 1980). There was speculation that the clusters may have been related to a common environmental etiology. Following the widely published diagnosis of the fourth cancer case in a football player in September 1987 the New Jersey Sports and Exposition Authority (NJSEA), managers of the complex, convened a medical committee to investigate whether environmental conditions present at the MSC might have played a role in the development of cancer in the four football players. A three-part plan--clinical, environmental, and epidemiologic--was developed. The first phase, an evaluation of the medical records of the four football players, confirmed all of the diagnoses. Additionally it established that the cancers were diagnosed six, four, one, and four years respectively after the players began working at the sports complex (Table 1). No common clinical factors were identified.
ENVIRONMENTAL ASSESSMENT The environmental assessment consisted of: 1. Review of all available data on air measurements for potentially toxic materials for the site and the surrounding areas. These data were limited since air contaminants were not routinely sampled at and around the MSC. 2. Direct measurements of volatile organic compounds (VOC) during the sum-
133
CANCER CLUSTER IN FOOTBALL PLAYERS TABLE1 POSITIONS AND DEMOGRAPHICS OF THE FOOTBALL PLAYERS DIAGNOSED WITH CANCER
Position
Age at diagnosis
Race
Cancer type
Year joined team
Year of diagnosis
Linebacker Running back Running back Lineman
26 31 23 27
White White White While
Lymphoma Gfioblastoma Angiosarcoma Hodgkin's disease
1976 1976 1983 1983
1980 1982 1984 1987
mertime to characterize any local increase due to soil outgassing during a time of the year when any soil emissions would be the highest. The sampling was important since the cases reported had been through the period 1980-1987 and if soil emissions were related to the occurrence of the cancer cases would still be representative. 3. Direct measurements of electric field strengths at sites within and surrounding the complex since three AM radio station towers are located at the MSC and five more are within 2-3 miles. These measurements were also necessary since the towers had been operational throughout the 1980-1987 period. For the second component of the environmental assessment the VOC samples were collected at three locations: the practice field, a natural grass field outside Giant Stadium, Giant stadium, and the race track as noted on Fig. 1. These sites were selected for two reasons: (1) the practice field and the stadium are the locations where the football players spent the greatest proportion of their time outdoors, and (2) the racetrack is a location where many outdoor MSC employees spend their workday exposed to the soil throughout the year. Sampling occurred during June-July 1988, a period coinciding with a major heat wave, which would act to enhance any local soil emissions. Samples were collected every third day at each location for an 8- to 9-hr period during daylight hours. They were collected on different types of Supelco carbotraps (S-III for vinyl chloride, C for heavy compounds) and the samples were analyzed on a Varic-3700 gas chromatograph. Analysis error ranged from 12 to 19% depending upon the compound. Mass spectral (Hewlett-Packard) verification was done on 15% of the samples. Air measurements for VOC had been made previously in the locker and weight rooms (NIOSH, 1987); no significant levels were recorded. Electric fields were measured with an electrical field strength meter (Instruments for Industry, S/N 12705-F) at randomized locations within the MSC and adjacent areas (Tell and Van Pelt, 1988). Measurements were taken inside and outside buildings, in parking lots, and near the New Jersey Turnpike. The average VOC concentrations found at each site are listed in Table 2 along with data previously collected at Lyndhurst, N J, a residential community approximately 3 miles from the MSC (Roytvarf, 1988). All data collected at the MSC were well below OSHA permissible exposure limits (United States Code of Federal Regulations Title 29, 1989) for employees at the site, and not significantly different from ambient values obtained in adjacent residential neighborhoods in Lyndhurst, NJ.
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KRAUT ET AL.
/
FIG. 1. Meadowlands Sports Complex site plan. (X) denotes location of VOC sampling.
Results of the electric field measurements revealed that outdoor AM radio broadcast field strengths at the MSC were in the uppermost 0.1% of field strengths measured in urban areas of the United States (Tell and Van Pelt, 1988). The root summed square (RSS) for all AM calling signals ranged from 0.013 to 9.63 V/m. The football players' locker room had a RSS of 0.0107 V/m. All indoor measurements were lower than those recorded outdoors. Further, electric field levels in the stadium were lower than those found in the stadium parking lot and along the New Jersey turnpike. In all cases these levels were lower than standards specifying human occupational exposures. Review of water drainage patterns found no indication that ground water from nearby toxic waste sites had contaminated soil within the sports complex. Soil within the complex consisted of fill brought from other locations, and this imported soil was separated from the marshlands by a cofferdam.
EPIDEMIOLOGIC ASSESSMENT The third phase of the investigation, an epidemiologic assessment, was undertaken to determine whether the pattern of deaths or of incident cancer cases
135
CANCER CLUSTER IN FOOTBALL PLAYERS
TABLE 2 AVERAGE CONCENTRATIONS OF VOC MEASURED AT THE MEADOWLANDS SPORTS COMPLEX AND 1N LYNDHURST, NJ Compounds (ppb)
PF
RT
GS
LND
Vinyl chloride Dichloromethane Ethylene chloride 2-Butanone Tetrahydrofuran 1,1,1-Trichloroethane Benzene Trichloroethylene Methylcyclohexane Toluene Tetrachloroethylene Ethylbenzene p- and rn-Xylene o-Xylene Trimethylbenzene Naphthalene
1.7 1.4 0.9 0.4 0.3 0.6 0.3 1.1 0.1 2.0 1.3 0.2 10.1 0.4 0.1 0.0
0.9 2.1 0.5 0.4 0.2 0.8 0.2 1.5 0.1 2.9 1.3 0.3 3.3 0.3 0. I 0.0
2.1 1.2 0.8 0.3 0.2 0.5 0.2 0.9 0.1 1.1 1.8 0.1 5.7 0.2 0.1 0.0
-1.9 0.8 1.0 0.3 0.8 0.2 1.6 0.4 2.5 0.9 0.3 4.1 0.2 0.1 0.0
Note. PF, practice field; RT, racetrack; GS, Giant Stadium; LND, Lyndhurst.
among the entire MSC workforce was different from that expected in New Jersey. Data were obtained on all cases of cancer in the workforce, but the cancer diagnoses of greatest concern were those developed in the football players and of leukemia. Leukemia was specifically investigated because a relationship between chronic exposure to electromagnetic fields and leukemia, although not conclusively established, has been suggested by epidemiologic studies (Wertheimer and Leeper, 1979; Milham, 1985; Ahlbom, 1988). METHODS Each of the 15 union and 8 employer groups represented at the complex was contacted and asked to provide lists of all their members or employees who had worked at the complex since it opened, along with their birth dates, social security numbers (SSN), date of hire, and duration of employment. Lists of cancer cases and of known deaths among these workers were also requested. The NJSEA provided a complete list of its payroll records. As a large number of these workers were part time or temporary, only workers who had worked at least 1 day in 2 calendar years were included in the study; 5787 MSC employees met these criteria. The Giants Football Club and one of the firms that managed security at the complex provided employment information on 957 and 1145 workers, respectfully. Two union groups provided demographic data on their membership totalling 458 individuals. A third union supplied morbidity and mortality information. Other employers and unions could not provide any of the requested information. In total 7889 individuals were included in the epidemiologic investigation. Birthdates were available for 2785 of these persons, and sex and race information was
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available for 1213 and 822 individuals, respectively. For approximately 90% of the cohort the last recorded address was in New Jersey. Due to the incomplete demographic information available for the cohort, proportionate mortality ratio (PMR) and proportional cancer incidence ratio (PCIR) studies were performed. Three sources were used to identify deaths among the cohort: the Social Security Administration (SSA), the National Death Index (NDI), and employer and union records. Individuals not identified as dead by any of these sources were presumed to be alive. In total, 235 deaths were identified in the cohort as having occurred between January 1, 1978 and December 31, 1987. A total of 228 death certificates, 97.0% of those sought, were obtained. To exclude individuals whose cancer diagnosis predated employment at the MSC, the date of diagnosis was obtained from information supplied by the New Jersey State Cancer Registry for those individuals who died in New Jersey with cancer. Four individuals who had developed cancer prior to September 1976 were removed from the analysis. One previously unidentiffed cancer death was discovered by the registry and was included in the PMR study. A total of 225 deaths were analyzed. Detailed analysis comparing the cost and utility of the various sources of decedent information is presented elsewhere (Kraut et al., in preparation). Death certificates were referred to a nosologist for standardized coding of cause of death. The PMR study was then performed using the PMR.BAS computer program (Maizlish, 1988). This program used United States death ratios in calculation of PMR rates. As 90% of the deaths occurred in New Jersey, computer tapes listing race- and sex-specific New Jersey deaths stratified by 5-year age intervals for the years 1977-1985 were purchased from MPDS (Mortality and Population Data System, University of Pittsburgh). New Jersey death ratios were computed for these years and converted into the PMR.BAS input format allowing for New Jersey-specific comparisons. Mortality ratios for 1986 and 1987 are extrapolated in linear fashion from 1985 rates. RESULTS: PMR STUDY Initial analysis was performed using US death ratios, but as these results did not differ significantly from those obtained using New Jersey deaths ratios, only the latter are presented. The MPDS data allowed calculation of New Jersey-specific mortality ratios for 32 causes of cancer death and 18 other conditions. Of the 225 deaths identified, 187 were in white males, 21 in nonwhite males, 13 in white females, and 4 in nonwhite females. Table 3 lists PMR data for white males alone and for all sex and race groups combined. Non-Hodgkin's lymphomas are classified with other lymphocytic diseases. In total 65 cancer deaths were observed (PMR 1.07; 95% CI 0.83-1.37). Nonstatistically significant elevated PMRs based on one, two, and one case were present for bone and bladder carcinoma and Hodgkin's disease, respectively. However, no overall or site-specific increased proportionate cancer mortality was observed in the MSC workforce. Specific attention was placed on identifying deaths from the types of cancer diagnosed in the football players and leukemia. The only death from a brain
137
CANCER CLUSTER IN FOOTBALL PLAYERS TABLE3 PROPORTIONATE MORTALITY RATIOSIN THE MSC WORKFORCE, 197~I987
White males a Obs All malignant neoplasms Cancer of digestive organs and peritoneum Cancer of lung Cancer of brain and other CNS sites Lymphosarcoma and reticulosarcoma Hodgkin's Disease Leukemia and aleukemia Cancer of other lymphatic tissue All lymphopoietic cancer Cirrhosis of liver All nonmalignant causes of death a
Exp
Obs/exp
50
49.80
1.00
11 22
13.20 17.28
1
All sex/race groups combined ~ 95% CI
Obs
Exp
Obs/exp
0.75-1.32
65
60.60
1.07
0.83-1.37
0.83 1.27
0.42-1.49 0.80-1.93
14 25
15.64 20.08
0.90 1.25
0.49-1.50 0.81-1.84
1,65
0.61
0.06--3.40
1
1.89
0,53
0.01-2.94
1 0 0
0.66 0.48 1.96
1.51 0.00 0.00
0.15-8.47 XXXX-3.44 XXXX-1.87
1 1 0
0.79 0.59 2.22
1,27 1.69 0.00
0
1.87
0.00
XXXX-1.96
2
2.21
0.90
0.10-3.27
1 13
4.97 6.33
1.71 2.05
0.02-1.73 1.0%3.51
4 13
5.81 7.40
0.69 1.75
0.1%1.76 0.94-3.00
137
137.20
1.00
0.84-1.18
0.97
0.83-1.14
160 164.40
95% CI
0,02-7.04 0.02-9.43 XXXX-1.65
N e w Jersey-specific mortality ratios are used in these comparisons.
neoplasm was in the football player already known to have this condition. N o additional deaths were coded to angiosarcoma. One white male died of lymphosarcoma. One white woman died of Hodgkin's disease and another of nonHodgkin's lymphoma. The only death certificate listing leukemia was for a nonwhite male who began working at the complex in 1977 and was diagnosed with multiple myeloma in 1978. This individual died of plasma cell leukemia in 1981. The nosologist coded the death to multiple myeloma. To assess the effect of latency, mortality ratios were compared for individuals dying less than and more than 5 years from the beginning of their employment at the complex. If environmental exposures at the stadium had contributed to the football players' cancer deaths, it is likely that a stronger effect would be seen in the group who had died more than 5 years after the start of employment. A total of 109 workers died within 5 years from their date of hire at the MSC, while 116 died more than 5 years after this date. The all malignancy PMR was 1.09 (95% CI 0.74-1.56) in the group dying less than 5 years and 1.06 (95% CI 0.74-1.47) in the group more than 5 years from date of hire. Thus, no trend with increasing latency was observed. Analysis of latency periods for the five diagnoses of particular concern--nonHodgkin's lymphoma, leukemia, Hodgkin's disease, brain tumors, and angiosarcoma--showed that only the brain cancer, diagnosed in the football player, and a case of Hodgkin's disease had occurred in workers more than 5 years after their initial date of hire at the MSC. To assess whether outdoor jobs, i.e., those with potentially increased environ-
138
KRAUT ET AL.
mental exposure (e.g., VOC or electromagnetic fields), were associated with increased cancer mortality, all jobs were classified by knowledgeable management personnel as either indoor, mixed, or outdoor. Classification was performed without knowledge of the job titles of deceased workers. All workers having mixed or outdoor jobs were termed to have nonindoor employment. In total, 72 deceased individuals, 62 white males, 9 nonwhite males, and 1 white female were classified as having nonindoor jobs. The female died of atherosclerotic heart disease. In this group 19 cancer deaths were observed versus 19.47 expected (PMR 0.98; 95% CI 0.5%1.52). The PMR for all malignancies for indoor workers was 1.12 (95% CI 0.82-1.49) based on 153 observed cases. Nonindoor workers did not die proportionately more frequently of cancer than indoor workers. Other than the two cancers detected in the deceased football players, no other deaths due to the diagnoses of concern were identified in nonindoor workers.
METHODS: PROPORTIONATE CANCER INCIDENCE RATIO STUDY Four sources were used to identify incident cancer cases: the New Jersey State Cancer Registry, death certificate review, employer and union records, and a questionnaire sent to all current employees asking whether they had ever been diagnosed as having cancer of any sort. Those answering yes were asked to sign a medical release form so that the diagnosis could be confirmed. Only individuals whose medical records contained a histological report confirming cancer were included in the analysis. A computer tape listing all cohort members was submitted for linkage to the New Jersey State Cancer Registry. Registry records are reportedly complete for the years 1979 through 1985. Partial listings are available for 1986 and 1987. New Jersey residents diagnosed with cancer in New York State, Pennsylvania, and Delaware are reported to the registry. A total of 132 individuals were reported as having cancer by the New Jersey State Cancer Registry after beginning employment at the MSC. An additional five individuals were found to have had cancer diagnosed prior to first employment at the complex and were not included in the study. The 82 deaths identified from the PMR study and all death certificates available for 1988 reporting cancer as either the cause of death or as a coexisting condition were included in this phase of the study. The date of cancer diagnosis was obtained from the New Jersey cancer registry in 45 cases. In 25 of the remaining cancer cases, date of diagnosis was approximated from the duration of cancer reported on the death certificate. For the remaining 12 cases, date of cancer diagnosis was approximated utilizing the clinical experience of the investigators and a recognized oncology source (De Vita et al., 1985). Date of diagnosis was presumed to be 6 months prior to death for four metastatic carcinomas of unknown origin, 1 year prior to death for seven lung cancers and for a case of "brain tumor" without histologic verification, and 2 years for one case of carcinoma of the floor of the mouth. In four deceased individuals cancer was diagnosed prior to beginning employment at the MSC; these workers were not included in the anal-
C A N C E R C L U S T E R IN F O O T B A L L P L A Y E R S
139
ysis. Thirty-seven cancer cases were identified from employer, union records, and the questionnaire. The termination date for the PCIR study was set at December 31, 1987 even though it is possible that some cancer cases were not identified for the years 1986 and 1987. This date was chosen instead of December 31, 1985, the final date for which the New Jersey cancer registry had near complete information, because it allowed for analysis of an additional 49 cases of cancer, 50% of the previous total, and added 2 years or 25% to the potential latency period. In addition one of the football players with cancer would not have been included in the study if the termination date had been set at December 31, 1985. In total, 146 individuals were identified to have developed cancer following employment at the MSC between January 1, 1978 and December 31, 1987. One person had two different cancers diagnosed and is treated in the analysis as two separate individuals giving a total of 147 cancers for analysis in the PCIR. Proportionate cancer incidence ratio data for New Jersey was obtained using a computer program developed by the New Jersey Department of Health (Hall and Livright, 1988). This program identifies 32 different cancer sites and using information obtained from the New Jersey State Cancer Registry calculates age, race, and New Jersey-specific cancer incidence for the years 1979-1984. Linear extrapolation of these data was performed for the years 1978 and 1985-1987. For white males both general population and blue collar rates are available. In this program angiosarcomas are classified with soft tissue tumors. Using the method of Rothman and Boyce (1983), 95% confidence intervals were calculated. RESULTS: PCIR STUDY Of the 147 cancer cases, 108 occurred in white males, 26 in white females, 8 in nonwhite males, and 5 in nonwhite females. As 73.5% of the cancer cases occurred in white males, the strongest inferences regarding cancer morbidity can be made regarding this group. No statistically significant excesses in cancer morbidity were observed at any anatomical site. Elevated PCIRs were seen for nasopharyngeal cancer and carcinoma of the breast in males, but these findings were based on only one observed case. Nonstatistically significant excesses of cancers of the oral cavity and pharynx were also found. A statistically significant decrease in the proportion of stomach cancers was observed. This finding is likely due to the overestimation of the expected values due to decreasing stomach cancer incidence rates (Maizlish, 1988). The small number of cases of cancer at specific sites in nonwhite males and in white and nonwhite females make analyses of these data difficult to interpret. Thus to utilize the information provided by these age and sex groups, overall cancer morbidity ratios were calculated combining all race and sex groups. Blue collar white male ratios were used for comparison in this analysis (Table 4). No statistically significant excesses were observed for Hodgkin's disease, nonHodgkin's lymphoma, soft tissue tumors, brain tumors, or leukemia. No additional cases of angiosarcoma were found. No unusual grouping of job titles were
140
K R A U T ET A L . TABLE 4 PROPORTIONATE CANCER MORBIDITY RATIOS IN THE M S C WORKFORCE, 1978-1987
White males
All cancers Oral cav. and pharnyx All digestive Stomach Trachea and lung Soft tissue Brain All lymphocytic Hodgkin's Non-Hodgkins Lymphoma All leukemias
Obs
Exp ~
108
108
Obs/exp
All sex/race groups combined 95% CI
Obs
Exp ~
147
147
Obs/exp
95% CI
7 21 0 30 2 1 8 4
3.78 24.61 3.19 27.61 0.94 1.77 6.43 2.81
1.85 0.85 0.00 1.09 2.14 0.57 1.24 1.42
0.74-4.40 0.53-t.27 XXXX-0.68 0.73-1.57 0.24-9.04 0.01-2.80 0.54--2.57 0.38-3.96
8 26 0 36 2 1 11 5
5.00 30.78 3.84 32.43 1.24 2.35 8.20 3.58
1.60 0.84 0.00 1.11 1.62 0.43 1.34 1.40
0.69-3.15 0.55-1.24 XXXX-0.96 0.78-1.54 0.18-5.85 0.01-2.37 0.67-2.40 0.45-3.26
4 1
3.62 2.86
1.10 0.35
0.30-2.90 0.00-1.55
6 2
4.63 3.57
1.30 0.56
0.47-2.82 0.06-2.02
Blue collar white male control ratios are used in calculating the expected valves.
found either for all cancer cases together or for individual diseases examined separately. Special attention was placed on examination of the cancer morbidity and mortality pattern of the Giants employees. Other than the four cases in the football players, two other cancer were identified in this group, both in office personnel. One man reported to have died of atherosclerotic heart disease had renal carcinoma concomitantly. The other died of lung cancer. Analysis was also performed of the incidence of cancers occurring more and less than 5 years from date of first hire at the MSC. In 82 cases cancer was diagnosed within 5 years of the date of hire, while in 65 cases the diagnosis was made more than 5 years after onset of employment. No significant excesses were observed for any of the diagnoses of concern when examination by latency was undertaken. Cancer morbidity ratios were quite similar for all of these diagnoses in both groups. A further analysis was performed comparing cancer incidence in the 101 indoor workers with the 46 nonindoor workers, Eight nonindoor workers had nonHodgkin's lymphoma, Hodgkin's disease, soft tissue cancers, or brain tumors. Four of these were the originally identified football players. Of the other four, three had non-Hodgkin's lymphoma, and one had Hodgkin's disease. The three cases of non-Hodgkin's lymphoma were observed in a parking toll collector, a security guard, and an operating engineer. Both cases of leukemia occurred in indoor workers. A nonstatistically significant increase in the PCIR for non-Hodgkin's lymphoma (2.33; 95% CI 0.63-5.97) was seen in nonindoor workers. This finding should be interpreted in conjunction with the fact that an overall excess in non-Hodgkin's lymphoma was not observed in the study population as a nonstatistically signifi-
CANCER CLUSTER 1N FOOTBALLPLAYERS
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cant decrease in the PCIR for this disease was seen in indoor workers (PCIR 0.69 95% CI 0.08--2.49).
DISCUSSION The negative results of the epidemiologic investigation are supported by the environmental measurements, which did not indicate any values above occupational guidelines or above typical urban levels in this area. The epidemiologic analysis, however, has a number of limitations. The first limitation is its low statistical power, or low ability to detect a significant excess of cancer cases if such an excess did actually exist. The low power of the study is due to the small number of expected cases with the cancer diagnoses of concern. Although 7889 individuals were entered into the cohort, based on the number of cancer cases observed only about 15 persons would have been expected to have had any of the diagnoses under study. The power of this investigation would be increased by reanalysis in the future when more cancer cases would have been expected to occur in the study population. A second limitation is that SSN were relied on heavily as the criteria for identifying deceased individuals. However, in certain cases a spouse or other family member may have also used the same number leading to misclassification. Although three such instances were detected, had we further identifying information more may have been discovered. A further limitation is that individuals who moved out of New Jersey and then developed nonfatal cancer would not have been identified by the state's cancer registry as having had cancer. It is highly unlikely, however, that a disproportionate number of the cancers of concern would self-select and move away from New Jersey. Therefore, this limitation does not appear to be major. The epidemiologic analyses presented in this report can be used only to estimate the past and current risk of cancer associated with employment at the MSC. Due to the long latency period of various forms of cancer, estimations of future cancer risk at the complex cannot be made from these data. However, if environmental conditions present at the sports complex led to the cancers reported in the football players, it is reasonable to suspect that other workers would have shown a similar excess cancer morbidity. Such an excess was not seen.
CONCLUSIONS An overall increase in cancer mortality was not observed in this study of employees of the Meadowlands Sports Complex. No increases in the proportion of cases of or deaths from leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, brain tumors, or angiosarcoma were found in the overall study population. No statistically significant excesses of cancer morbidity or mortality were observed for any specific type of cancer. In our opinion, based on the available clinical, environmental, and epidemiologic data, the four cases of cancer diagnosed in the professional football players were most likely related to chance and not to environmental conditions present at the MSC.
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The three-phase evaluation--clinical, environmental, and epidemiologic-undertaken in this study proved useful in addressing the concerns of the workforce and management of the MSC as well as those of the citizens of the nearby communities. The strengths of our approach were that all potentially concerned groups were contacted and asked to participate, all available data and pertinent databases were utilized, and a structured systematic plan was outlined both prior to initiation and following through to completion of the investigation. The approach outlined in this report may thus serve as a model for other investigators studying similarly highly visible cancer clusters.
ACKNOWLEDGMENTS The authors acknowledge the assistance of the administration, staff, and unions working at the MSC in conducting this study. Also the help of W. Tell, PhD., W. Van Pelt, PhD., and Mr. B. Roytvarf in performing the environmentalsampling and D. Micheals, PhD., and N. Hall, PhD. in assisting with the epidemiologic analysis were most appreciated.
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