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Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Cancer Incidence among Foundry Workers in Denmark a
b
David Sherson M.D. , Ole Svane M.D. & Elsebeth Lynge Ph.D.
c
a
Department of Occupational , Medicine Vejle , Sygehus Vejle, Denmark
b
Danish Labour Inspection Service , Copenhagen, Denmark
c
Danish Cancer Registry Danish Cancer Society , Copenhagen, Denmark Published online: 03 Aug 2010.
To cite this article: David Sherson M.D. , Ole Svane M.D. & Elsebeth Lynge Ph.D. (1991) Cancer Incidence among Foundry Workers in Denmark, Archives of Environmental Health: An International Journal, 46:2, 75-81, DOI: 10.1080/00039896.1991.9937432 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9937432
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Cancer Incidence among Foundry Workers in Denmark
D A M D SHERSON, M.D. Department of Occupational Medicine Vejle Sygehus Vejle, Denmark OLE SVANE, M.D. Danish labour Inspection Service Copenhagen, Denmark ELSEBETH LYNGE, Ph.D. Danish Cancer Registry Danish Cancer Society Copenhagen, Denmark
ABSTRACT. Cancer incidence was studied among 6 144 male foundry workers who were invited to participate in either of two Danish national silicosis surveys conducted during 1%7-1969 and 1972-1974. Cancer incidence was followed through to the end of 1985 by computerized linkage to the Danish Cancer Registry, and Standardized Morbidity Ratios (SMRs) were calculated based on incidence rates for the Danish population. For the entire cohort, significantly elevated SMRs were seen for all cancers (SMR, 1.09; 95% CI, 1.01-1.18) and lung cancer (SMR, 1.30; 95% CI, 1.12-1.51), and SMRs were at the borderline of statistical significance for bladder cancer (SMR, 1.24; 95% GI, 0.97-1.59). Excess lung and bladder cancer risk were confined to workers who had worked in foundries for at least 20 y, There was a positive correlation between silicosis prevalence in employees at the foundries at the time of the x-ray examinations and lung cancer incidence during the follow-up period. Squamous cell carcinomas, anaplastic carcinomas, and other lung cancers accounted for the excess lung cancer risk, whereas there was not excess risk among the foundry workers for adenocarcinomas of the lung.
THE INTERNATIONAL AGENCY for Research on Cancer concluded in 1987 that iron and steel foundry work is carcinogenic to humans.' Cohort studies of workers conducted in many countries have typically noted risks of lung cancer elevated between 1.5- and 2.5-f0ld.~-" Foundry workers are exposed to many substances, of which the most important are silica dust; metallic fumes; carbon monoxide; and pyrolysis products, including polynuclear aromatic compounds. Phenol, formaldehyde, furfuryl alcohol, isocyanate, and amines are ingredients in the binders.12 It is still unknown which exposures in the work environment are responsible for increased lung cancer risk among foundry workers. March/April 1991 [Vol. 46 (No. 2)]
Risk of silicosis among foundry workers has been of concern for decades, and to control for this disease x-ray examinations were performed on all foundry workers in Denmark during 1967-196913 and 19721974.j4 In the present study, cancer incidence has been followed up to the end of 1985 for all workers who were invited to participate in those examinations, and cancer incidence has been analyzed by work tasks and x-ray status determined during the initial surveys. Materials and methods Population. The study population included all male foundry workers who were invited to either of the two 7.5
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x-ray examinations conducted during 1967-196913 and 1972-1974.14The first study included all Danish iron (n = 57) and steel (n = 1) foundries, and the second study was expanded to include all metal foundries (n = 53). Data, including detailed work histories until date of x-ray examination and the chest x-ray results, are stored in the Danlish Labour Inspection Service’s register on silicosis in Danish foundrie~.’~ Unfortunately, data on tobacco consumption were not recorded, and no data were available on the work histories after the x-ray examinations occurred. A previous mortality study included 5 579 male production workers who registered for the two examinations.16 In the present study, the population was supplemented with 482 managerial persoris and with 84 persons who were not included in the original register (they had been invited to the earlier examinations but did not participate). Also, a few persons in the original register did not participate. Therefore, the present study included 6 054 male participants, and 91 male nonparticipants (1 of whom is excluded from analysis; see Table 1). Follow-up for death and emigration. Personal identification numbers were introduced in Denmark on 1 April 1968.17Therefore, the majority of cohort members had personal identification numbers, and they were followed up for deaths and emigrations by linkage with the Central Population Register. The few cohort members without personal identification numbers were all traced manually through the municipality population registers. Registration of cancer cases. A population-based cancer registration commenced in Denmark in 1943, and all patients who were living as of 1 April 1968 were registered with personal identification numbers. For cohort members with identification numbers, notified cancer cases were identified by linkage with the Cancer Register. For cohort members without identification numbers, notified cancer cases were identified by manual check of lists of cancer patients of equivalent sex and date of birth. Cancer cases notified between 1943 and 1977 were coded according to a modified version of the seventh revision of the International Classification of Diseases, ICD-7.’’ Cancer cases notified from 1978 to the present were coded according to the International Classification of Diseases for Oncology, ICD0.’’ Both classifications could distinguish the main histological types of lung cancer. Calculation of expected number of cancer cases. For each individual person years at risk were calculated using the date of the first x-ray examination in which the person participated. Fictive dates of x-ray examination were given to nonparticipants: 1 July 1967 was used for the first survey, and 1 January 1973 was used for the second survey. Person years at risk were calculated un. ti1 death, emigration, or end of follow-up on 31 December 1985. All tumors that were diagnosed during the individual risk periods were included in the analyses. Among the cohort of 6 144 mates, 647 tumors were identified, of which 532 were first tumors and 115 were second (or subsequent) tumors. Expected numtars were based on cancer incidence rates for the Danish population for sex, 5-y age groups, 76
and the following calendar periods: 1963-1967, 19681972, 1973-1 977, 1978-1 982, and 1983-1 985. The PYRS program was used for calculation of expected numbers.” Standardized morbidity ratios (SMRs) were calculated by dividing the observed number of cancer cases (obs.) by the expected number (exp.). Ninety-five percent two-tailed confidence intervals (95% CI) were calculated based on the assumptions that the observed number of cases followed a Poisson distribution,2’ and that for observed numbers over 30, a normal distribution would result.22 Results
Overall results of cancer incidence among the foundry workers are presented in Table 2, Only SMRs for all malignant neoplasms (SMR, 1.09; 95% CI, 1.01-1.18) and for lung cancer (SMR, 1.30; 95% CI, 1.12-1.51) were statistically significantly elevated. The SMR for bladder cancer was elevated at the borderline of statistical significance (SMR, 1.24, 95% CI, 0.97-1.59). The cancer risk was particularly elevated for the small group of 90 foundry workers who did not participate in the x-ray examination (Table 3). Table 4 describes the lung and bladder cancer incidence according to accumulated length of employment in foundries upon entry into the follow-up period. A progressive increase in SMRs was observed as length of employment increased. Statistically significantly elevated risks, or risks at the borderline of statistical significance, were seen for both lung and bladder cancer among foundry workers who had been employed at least 20 y. Table 5 describes lung and bladder cancer incidence according to foundry job at the onset of the follow-up period. A statistically significant excess risk for lung cancer was found for workers from metal foundries (SMR, 2.13; 95% CI, 1.19-3.52). A borderline significant excess for lung cancer was found for workers who were employed in iron and steel foundries (SMR, 1.21; 95% CI, 0.98-1.50). Bladder cancer incidence was significantly elevated among workers with unspecified jobs in iron foundries (SMR, 2.83; 95% CI, 1.14-5.84). Lung cancer incidence among foundry workers with and without silicosis at the time of entry into the followup period is shown in Table 6 . Silicotics and nonparticipants had the highest SMRs: 1.71 and 2.66, respectively. Because these groups are relatively small, none
Table 1.-Number of Male Foundry Workers Invited to the 1967-1969 and 1972-1974 X-Ray Examinations in Denmark X-ray examination
Participants Nonparticipants Analyzed data set
1967-1969
1972-1974
Total
3 959 49 4008
3 839 70
6 054
3909
91 * 6 145*
*One person was dead before fictive date of x-ray examination and was not included in the analyses.
Archives of Environmental Health
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Table 2.-Obserwd and Expected Number of Cancer Cases in Male Foundry Workers in Denmark 1967-1985 (No latency Period) ICD-7
Cancer
ObS.
Exp.
SMR
140-205 140 141 142 143-144 145-148 150 151 152 153 154 155.0 155.1 156 157 158-1 59 160 161 162.0,l 162.2 163 164 170 177 178 179
All malignant neoplasm Lip Tongue Salivary glands Mouth Pharynx @sop hagus Stomach Small intestine Colon Rectum Liver Gallbladder Liver (not primary) Pancreas Peritoneum Nasal cavities Larynx Lung Pleura Lung (not primary) Mediastinum Breast Prostate Testis Other and unspecified genital organs Kidney Bladder Melanoma of skin Other skin Eye Brain Thyroid Endocrinal glands Bone Connective tissue Metastates Other and unspecified sites Non-Hodgkin lymphoma Hodgkin’s disease Multiple myeloma Leukemia Mycosis fungoides
647 11 4 1 4 6 6 34 2 37 30 7 4 4 18 1 1 16 166 1 2 2 2 50 9 1
594.41 8.28 1.57 1.29 3.10 4.00 6.93 29.61 1.83 39.54 33.57 6.52 4.20 2.36 20.03 1.50 1.70 11.11 127.84 2.59 0.92 0.50 1.00 50.45 8.25 2.13
1.09 1.33 2.54 0.77 1.29 1.50 0.87 1.15 1.09 0.94 0.89 1.07 0.95 1.69 0.90 0.67 0.59 1.44 1.30 0.39 2.17 4.01 2.00 0.99 1.09 0.47
1.010.660.690.020.350.550.320.820.130.680.600.430.26-
18 63 9 65 2 13 3
0.91 1.24 0.90 0.93 1.18 0.85 1.71
0.540.970.410.730.140.450.35-
1.43 1.59 1.71 1.19 4.27 1.45 5.01
1 1 8 5
19.86 50.93 9.98 69.86 1.69 15.36 1.75 0.87 0.93 1.91 8.71 4.77
1.08 0.52 0.92 1.05
0.030.010.400.34-
5.99 2.92 1.81 2.45
11 7 4 17 1
11.34 3.79 6.23 15.18 0.42
0.97 1.85 0.64 1.12 2.40
0.48- 1.74 0.74- 3.80 0.18- 1.64 0.65- 1.79 0.06-13.26
180 181 190 191 192 193 194 195 196 197 198 199 200, 202 201 203 204 205
0
95% CI 1.18 2.38 6.52 4.32 3.30 3.27 1.88 1.61 3.95 1.30 1.28 2.21 2.44 0.46- 4.34 0.53- 1.42 0.02- 3.71 0.01- 3.28 0.82- 2.34 1.12- 1.51 0.01- 2.15 0.29- 7.85 0.48-14.44 0.24- 7.22 0.74- 1.31 0.55 2.07 0.01- 2.62
-
-
I
Table 3.-Observed and Expected Number of All Cancer and Lung and Bladder Cancer Cases in Male Foundry Workers, by Participation in X-ray Examination (No latency Time)
ICD-7
No. of persons
Obs.
Exp.
SMR
95% CI
6054 90
633 14
585.69 8.72
1.08 1.61
1.00-1.17 0.88-2.69
6054 90
161 5
125.96 1.88
1.28 2.66
1.10-1.49 0.86-6.21
6 054
62 1
50.17 0.76
1.24 1.32
0.97-1.59 0.03-7.33
t 140-205 162.0,l 181
March/AprillWl [Vol. 46 (No. 2)]
All malignant neoplasms Participants Nonparticipants Lung Participants Nonparticipants Bladder Participants Nonparticipants
90
Table 4.-Observtd and Expected Number of Lung Cancer Cases and Bladder Cancer Cases in Male Foundry Workers by Number of Years Accurnul,ited in Foundries at Date of X-ray Examination (No latency Period)
?
1
No. of
Lung cancer
Years in foundry
persons
Obs.
Less than 10 y 10-19 y 20-29 y 2 30 y Years not stated Nonparticipants
3 386 1127 900 613 28
All
1
Bladder cancer
EXP.
SMR
95% CI
Obs.
Exp.
SMR
95% CI
41.62 28.53 29.61 25.93 0.27 1.88
0.99 1.19 1.28 1.85
0.73-1.34 0.85-1.67 0.93-1.76 1.39-2.45
0.46-1.40 0.48-1.73 1.05-2.66 0.96-2.65
-
2.66
0.86-6.21
1
16.81 11.35 11.63 10.28 0.1 1 0.76
0.83 0.97 1.72 1.65
-
14 11 20 17 0
90
41 34 38 48 0 5
1.32
0.03-7.33
6 144
166
127.84
1.30
1.12-1.51
63
50.93
1.24
0.97-1.59
-
-
I I
I
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Table 5.-ObservixI and Expected Number of Lung Cancer Cases and Bladder Cancer Cases in Male Foundry Workers by Workplace in Foundries at Date of X-ray Examination (No Latency Period) No. of Years in foundry
I 1
Iron and steel foundry Foundry* Core room Finishing Unspecified Metal foundry Not foundry Workplace not stated Nonparticipants
All
Lung cancer
Bladder cancer
EXP.
SMR
95% CI
Obs.
Exp.
SMR
95% CI
85 13 28 9 15 11 0 5
70.22 9.91 24.37 6.18 7.03 8.00 0.26 1.88
1.21 1.31 1.15 1.46 2.13 1.37
0.98-1 .50 0.70-2.24 0.76-1.66 0.67-2.76 1.19-3.52 0.69-2.46
0.81-1.61 0.28-2.61 0.42-1.76 1.14-5.84 0.79-4.70 0.34-3.22
-
-
-
2.66
0.86-6.2 1
1
28.01 3.92 9.71 2.47 2.78 3.18 0.10 0.76
1.14 1.02 0.93 2.83 2.16 1.26
-
32 4 9 7 6 4 0
1.32
0.03-7.33
166
127.84
1.30
1.12-1.51
63
50.93
1.24
0.97-1.59
persons
Obs.
3 377 45 1 1 071 330 485 312 28 90 6 144
I
*Moulders, oven workers, casters, crane operators, and shake-out.
I
I
Table 6.-Observed and Expected Number of Cancer Cases in Male Foundry Workers, by Silicosis Diagnosis at X-ray Examination (No Latency Time) No. of persons
Participants Diagnosed with silicosis at x-ray examination Not diagnosed with silicosis Nonparticipants
All
Exp.
SMR
95% CI
144
11
6.43
1.71
0.85-3.06
5 910 90
150 5
119.53 1.88
1.25 2.66
1.07-1.47 0.86-6.21
6 144
166
127.84
1.30
1.12-1.51
of these risks was statistically significantly elevated. The large group of ncinsilicotics had a significantly elevated lung cancer risk (SMR, 1.25; 95% CI, 1.07-1.47). Iron and steel foundries were subdivided according to prevalence of silicosis per 1 OOO workers at the first x-ray examinatiori in 1967-1969. Table 7 shows an increasing incidence of lung cancer, which corresponds to increasing prevalence of silicosis. A significantly elevated risk was iiound among workers coming from foundries with 40-250 silicotics per 1 OOO (SMR, 1.40; 95% CI, 1.16-1.76). Lung cancer cases were divided into four histologic types. Excess lung cancer risk among the foundry work78
Obs.
ers came from both squamous cell carcinomas (SMR, 1.42; 95% CI, 1.13-1.791, anaplastic carcinomas (SMR, 1.30; 95% CI 0.96-1.761, and other lung cancers (SMR, 1.28; 95% CI 0.89-1.781, whereas the number of adenocarcinomas was close to the expected number for all Danish men (SMR, 1.04; 95% CI 0.64-1.65).
Discussion The present study showed a moderately increased risk of lung cancer among foundry workers in Denmark (SMR, 1.30; 95% CI, 1.12-1.51). This excess risk is slightly lower than that found for foundry workers in Archives of Environmental Health
Table 7.-Observed and Expected Number of Lung Cancer Cases in Male Foundry Workers by Prevalence of Silicosis in the Company at the First X-ray Examination (No latency Time)
No. of persons
Obs.
Exp.
SMR
95X CI
24.24 39.39 53.67 7.03
0.60-1.42 0.89-1.58 1.16-1.76 1.19-3.52 0.02-3.40 0.86-6.21 1.12-1.51
t Iron and steel foundries 0 silicoticsll OOO 1-39 silicoticsll OOO 40-250 silicotics/l OOO Metal foundries Others Nonparticipants
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I
1468
1 820 2 174 485 107 90
All
6 144
Table 8.-Observed and Expected lung Cancer Cases in Male Foundry Workers by Histology (No latency Time)
Histology Squamous cell carcinomat Adenocarcinoma Anaplastic carcinoma All others Total
71
50.16
1.42
18 42 35
17.29 32.37 27.42
1.04 0.62-1.65 1.30 0.96-1.76 1.28 0.89-1.78
166
127.24
1.30
1.13-1.79
1.12-1.51
*The standard rates used in this calculation were based on a later version of the cancer register than those used in the other tables. Therefore, the expected number of lung cancers is 127.24 in this table, but is 127.84 in the other tables. tlncludes “solid carcinoma, NOS.”
other countries where the risk estimates have normally been in the range of 1.5-2.5.’-” The Danish study is based on cancer incidence data, whereas the previous studies have been based on mortality data. With respect to lung cancer, however, this should not distort the comparison between foundry workers and the respective national populations. The Danish study population was collected from nationwide surveys where all workplaces were included independently of the work environment. Good tracing possibilities in Denmark insured that all invited foundry workers were traced successfully and followed up. However, only an average of 15 y had elapsed between x-ray examinations and the end of the follow-up period. More than half of the workers reported that they had worked in the foundries for less than 10 y. Lung cancer risk increased with number of years accumulated in foundry work upon entry into the followup period. The risk for workers who had less than 10 y employment was similar to that of all Danish men (SMR, 0.99; 95% CI, 0.73-1.341, and risk increased almost twofold for workers who had been employed for at least 30 y (SMR, 1.85; 95% CI, 1.39-2.45). Concomitant increases in lung cancer risk and in duration of employment in foundries has also been observed in the United Kingdomg and Poland.” In the present March/Aprill991 [Vol. 46 (No. Z)]
23 47 75 1 5
1.64
1.88
0.95 1.19 1.40 2.13 0.61 2.66
166
127.84
1.30
15
study, the cohort was constructed from cross-sectional data. Regardless of date of employment, only those workers who remained in their foundry jobs until the x-ray examinations took place were included in the present study. Therefore, analysis of the data by time since first employment is not meaningful. When the cohort members were divided according to work tasks at the time of the x-ray examination, only the small subgroup of workers from the metal foundries had a significantly elevated lung cancer risk (SMR, 2.13; 95% CI, 1.19-3.52). There were only slight differences in the lung cancer risk between the four groups of workers from the iron and steel foundries. Previous studies have pointed to finishing” or fettling workg and furnace workg as being the jobs in iron foundries with the highest lung cancer risk. However, this pattern was not seen among Danish foundry workers. A possible explanation may be that many of the workplaces were small, and workers often helped each other at different jobs. Therefore, no attempt was made to divide the foundry workers into categories according to levels of potential workplace exposures, e.g., based on measurements recorded in the literature. Furthermore, there was an association between job title and length of employment. Core makers and hand moulders were skilled workers who had long seniority in their trade, whereas finishing workers were unskilled workers and normally had short seniority. The etiology for the increased lung cancer risk among long-term foundry workers is uncertain because foundry workers are exposed to many chemical compounds.” The availability of x-ray examinations allowed us to look further into the relationship between silica exposure and lung cancer. The highest lung cancer risk was found among workers who were diagnosed with silicosis at the x-ray examinations (SMR 1.71) and among workers who did not participate for various reasons, including illness (SMR 2.66). The cases in these groups, however, comprised only 16 of 166 observed lung cancer cases, and there was a significant, moderately increased lung cancer risk (SMR, 1.25; 95% CI, 1.07-1.47) among the majority of workers without silicosis at the start of the 15-y follow-up period. Furthermore, a trend existed where workers from foundries where there were no cases of 79
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silicosis had a lung cancer risk similar to that of all Danish men SMF: (0.951,whereas workers from foundries where there was a high prevalence of silicosis had 95% significantly elevated lung cancer risk, (SMR, 1.a; CI, 1.16-1.76). The concomitant increase in SMRs for lung cancer with increasing silicosis prevalence suggests a dose-response relationship between lung cancer and silica exposure. When interpreting these results, it should be remembered that the presence of silicosis was known only upon entry into the follow-up period. Furthermore, a high prevalence of silicosis might indicate a generally poor work environment, including exposure to other potentially carcinogenic substances. The diagnosis was based on a full-sized chest x-ray interpreted by the same expert using the International Labor Organization‘s Classification of Pneumoconiosis from 1958.13-14However, a minor degree of misclassification cannot be excluded, and a normal x-ray does not completely exclude the presence of silica-induced pulmonary fibro~is.’~ There has been considerable interest in polycyclic aromatic hydrocarbons (PAHs) (e.g., benzo(a)pyrene) as possible causative factors for the excess lung cancer risk that exists among foundry workers. Air particulates in foundry air can be mutagenic.24Benzo(a)pyrene adducts have been detected in blood samples from foundry workers, and there may be a dose-response relationship between adduct level and environmental contamirtati~n.’~,’~ Also, there is experimental evidence that higher intracellular levels of benzo(a)pyrene can be achieved when there is simultaneous exposure to silica particle^.^' Our data do not allow an analysis of the lung cancer risk according to level of PAH exposure. Exposure to nickel and chromium may occur in the metal foundries, and the significantly increased lung cancer risk among workers from the metal foundries may reflect exposure to those metals. Many attempts have been made to correlate histologic subtypes oi lung cancer with oc~upation.’~-~’ These studies are difficult because tobacco consumption is related to all major cell types.30 There are, however, some suggestions of occupationally related correlations. Small-cell carcinomas appear to be related to bischloromethyl ether and uranium exposure. Adenocarcinomas are often seen in connection with asbest,os exposure. Evidence exists that squamous cell carcinomas may be related to chromate, nickel, and PAH e~posure.’~,~’ The histology data may vary, however, depending on the use of different classification systems and the specimen source. The interobserver variability may be as high as 42°/0.28 Our data show that the excess lung cancer risk among foundry workers results from squamous cell carcinomas, anaplastic carcinomas, and the residual group of other cancers. The foundry workers’ risk for adenocarcinomas of the lung was equivalent to that of all Danish men. It is unlikely that bias as a result of specimen source or interobserver variability would invalidate these data because any bias would probably be consistent across the Danish population. 80
The fact that both lung and bladder cancer risks were increased among the foundry workers could raise suspicion to confounding from tobacco smoking. There were, however, only minor differences in the smoking pattern across socioeconomic groups in Denmark around 1970,32and the fact that both the increased lung and bladder cancer risks were confined to longterm workers points to an occupational etiology. The mortality from bladder cancer has been reported in only four of the previous studies on foundry workers. A slight excess risk of bladder cancer was indicated in three studies from the United state^,^,^^'^ but not in a study from the United K i n g d ~ m The . ~ excess bladder cancer risk in Denmark was seen only for long-term foundry workers, and the results for entire cohorts will probably depend on the composition of the cohorts according to length of employment. There was no association between foundry work and bladder cancer in the U.S. National Bladder Cancer Study in which foundry work was considered if the job was held for at least 6 mo and smoking was controlled for in the analysis.”,” Exposure to aromatic amines formed from the binders is a possible explanation for the excess bladder cancer risk in long-term foundry workers. In conclusion, the present study demonstrated increased lung and bladder cancer incidence among long-term foundry workers in Denmark. The data suggest a dose-response relationship between silica exposure and lung cancer incidence. Excess lung cancer risk was confined to squamous cell carcinomas, anaplastic carcinomas, and other lung cancers, whereas there was no excess risk from adenocarcinomas of the Iung.
********** Submitted for publication March 22, 1990; revised; accepted for publication October 1, 1990. Requests for reprints should be sent to: David Sherson, Dept. of Occupational Medicine, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark.
********** References
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Kingdom steel foundry workers: 1946-85. Br J Ind Med 1989; 46: 74-81. Silverstein MM, Maizlish N, Park R, Silverstein B, Brodsky L, Mirer F. Mortality among ferrous foundry workers. Am J Ind Med 1986; 10: 27-43. Becher H, Jedrychowsky W, Flack E, Gomola K, Wahrendorf I. Lung cancer, smoking, and employment in foundries. Scand J Work Environ Health 1989; 15: 38-42. International Agency for Research on Cancer. Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol 34. Polynuclear Aromatic Compounds. Part 3. Lyon: IARC, 1984, p 145. Frost J. Silicoseundedgelsen af stdberiarbejdere 1967-1969. (Prevalence of silicosis in Danish iron and steel foundries). Socialt Tidsskrift 1972; 48/7-8: 1-26. Frost J. Silicoseundedgelsen af stdberiarbejdere 1972-1974. (Silicosis study of foundry workers 1972-1974). Kdbenhavn: Uirektoratet for arbejdstilsynet, 1979. Arbejdstilsynet. Forskrifter for arbejdstilsynets register over silikoseforekomst i danske stdberier. (Regulations for the Danish Labour Inspection Service register on silicosis in Danish foundries). Kdbenhavn: Arbejdstilsynets bekendtgdrelse af 5. Septem:ber 1984. Shemn D, lversen E. Mortality among foundry workers in Denmark due to cancer and respiratory and cardiovascular diseases. In: Goldsmith 0,Winn DM, Shy CM, Eds. Silica, silicosis and cancer: controversy in occupational medicine. New York: Praeger, 1986: 403-14. National Centre for Health Statistics. The person number system of Sweden, Noway, Denmark and Israel. Vital Health Statistics. Ser 2-no 84, DHHS Publn. PHS 80-1358, Hyattsville, 1980. Clemmesen I. Statistical studies in the aetiology of malignant neoplasms. IV. Denmark 1943-67. Ada Pathol Microbiol Scand 1974; Suppl 247. World Health Organization. International classification for oncology (KO-0). WHO, Geneva, 1976. Coleman M, Douglas A, Hermon C, Pet0 J. Cohort study analysis with a Fortran computer program. Int J Epidemiol 1986; 15: 134-37. Bailar JC, Ederer F. Significance factors for the ratio of a poisson variable to its expectation. Biometrics 1964; 2 0 339-43. Keiding N, Andersen PK. Samtidig analyse af flere forklarende variable. Modeller for statistisk variation. (Simultaneous analysis of several explanatory variables. Models for stocastic variation). In: Andersen 0. Ddelighed og erhverv 1970-80. (Occupational
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mortality in Denmark 1970-80). Statistiske underdgelser nr. 41. Kdbenhavn, Danmarks Statistik, 1985, pp. 1 1 1-26. Craighead JE, Vallgathan NV. Cryptic pulmonary lesions in workers occupationally exposed to dust containing silica. JAMA 1980; 240: 1939-41. McCalla DR, Kaiser C, Kerr A, Gibson ES, Lockington JN: Mutagenicity of air particulates in a steei foundry. Can J Genet Cytol 1979 21: 569-70. Autrup H, Seremet T, Sherson D. Quantitation of polycyclic aromatic hydrocarbon-serum protein and lymphocyte DNA adducts in Danish foundry workers using immunoassays. In: Garner RC, Ed. Biomonitoring and carcinogen risk assessment. Oxford: Oxford University Press, 1990 (in press). Perera FP, Hemminki K, Young TL, Brenner D, Kelly C, Santella RM. Detection of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. Cancer Res 1988; 48: 2288-91. Lakowiu JR, Beran DR. Effects of adsorption of benzo(a)pyrene to asbestos and non-fibrous mineral particulates upon its rate of uptake into phospholipid vesicles and rat liver microsomes. In: Brown RC, Gormley IP, Chamberlain M, Davies R,, eds. The in vitro effects of mineral dusts. London: Academic Press, 1980; 169-75. lves JC, Buffler PA, Greenberg SD. Environmental associations and histopathologic patterns of carcinoma of the lung: the challenge and dilemma in epidemiologic studies. Am Rev Respir Dis 1983; 128 195-209. Morton WE, Treyve EL. Histologic differences in occupational risks of lung cancer incidence. Am J Ind Med 1982; 33: 441-57. Stayner LT, Wegman DH. Smoking, occupation, and histopathology of lung cancer: a case-control study with the use of the Third National Cancer Survey. J Natl Cancer lnst 1983; 5 6 421 -25. Vena JE, Byers TE, Cookfair 0,Swanson M. Occupation and lung cancer risk: an analysis by histologic subtypes. Cancer 1985; 5 6 910-17. Nielsen PE, Zacho J, Olsen JA, Olsen CA. findringer i danskernes rygevaner 1970-1987 (Alteration in the Danes’ smoking habits in the period 1970-1987). Ugeskr Laeger 1988; 150 2229-33. Silverman DT, Levin LI, Hoover RN, Hartge P. Occupational risks of bladder cancer in the United States: I. White men. J Natl Cancer lnst 1989; 81: 1472-80. Silverman DT, Levin LI, Hoover RN. Occupational risks of bladder cancer in the United States. II. Nonwhite men. J Natl Cancer lnst 1989; 81: 1480-83.
81
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Cancer Incidence among Foundry Workers in Denmark a
b
David Sherson M.D. , Ole Svane M.D. & Elsebeth Lynge Ph.D.
c
a
Department of Occupational , Medicine Vejle , Sygehus Vejle, Denmark
b
Danish Labour Inspection Service , Copenhagen, Denmark
c
Danish Cancer Registry Danish Cancer Society , Copenhagen, Denmark Published online: 03 Aug 2010.
To cite this article: David Sherson M.D. , Ole Svane M.D. & Elsebeth Lynge Ph.D. (1991) Cancer Incidence among Foundry Workers in Denmark, Archives of Environmental Health: An International Journal, 46:2, 75-81, DOI: 10.1080/00039896.1991.9937432 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9937432
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Cancer Incidence among Foundry Workers in Denmark
D A M D SHERSON, M.D. Department of Occupational Medicine Vejle Sygehus Vejle, Denmark OLE SVANE, M.D. Danish labour Inspection Service Copenhagen, Denmark ELSEBETH LYNGE, Ph.D. Danish Cancer Registry Danish Cancer Society Copenhagen, Denmark
ABSTRACT. Cancer incidence was studied among 6 144 male foundry workers who were invited to participate in either of two Danish national silicosis surveys conducted during 1%7-1969 and 1972-1974. Cancer incidence was followed through to the end of 1985 by computerized linkage to the Danish Cancer Registry, and Standardized Morbidity Ratios (SMRs) were calculated based on incidence rates for the Danish population. For the entire cohort, significantly elevated SMRs were seen for all cancers (SMR, 1.09; 95% CI, 1.01-1.18) and lung cancer (SMR, 1.30; 95% CI, 1.12-1.51), and SMRs were at the borderline of statistical significance for bladder cancer (SMR, 1.24; 95% GI, 0.97-1.59). Excess lung and bladder cancer risk were confined to workers who had worked in foundries for at least 20 y, There was a positive correlation between silicosis prevalence in employees at the foundries at the time of the x-ray examinations and lung cancer incidence during the follow-up period. Squamous cell carcinomas, anaplastic carcinomas, and other lung cancers accounted for the excess lung cancer risk, whereas there was not excess risk among the foundry workers for adenocarcinomas of the lung.
THE INTERNATIONAL AGENCY for Research on Cancer concluded in 1987 that iron and steel foundry work is carcinogenic to humans.' Cohort studies of workers conducted in many countries have typically noted risks of lung cancer elevated between 1.5- and 2.5-f0ld.~-" Foundry workers are exposed to many substances, of which the most important are silica dust; metallic fumes; carbon monoxide; and pyrolysis products, including polynuclear aromatic compounds. Phenol, formaldehyde, furfuryl alcohol, isocyanate, and amines are ingredients in the binders.12 It is still unknown which exposures in the work environment are responsible for increased lung cancer risk among foundry workers. March/April 1991 [Vol. 46 (No. 2)]
Risk of silicosis among foundry workers has been of concern for decades, and to control for this disease x-ray examinations were performed on all foundry workers in Denmark during 1967-196913 and 19721974.j4 In the present study, cancer incidence has been followed up to the end of 1985 for all workers who were invited to participate in those examinations, and cancer incidence has been analyzed by work tasks and x-ray status determined during the initial surveys. Materials and methods Population. The study population included all male foundry workers who were invited to either of the two 7.5
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x-ray examinations conducted during 1967-196913 and 1972-1974.14The first study included all Danish iron (n = 57) and steel (n = 1) foundries, and the second study was expanded to include all metal foundries (n = 53). Data, including detailed work histories until date of x-ray examination and the chest x-ray results, are stored in the Danlish Labour Inspection Service’s register on silicosis in Danish foundrie~.’~ Unfortunately, data on tobacco consumption were not recorded, and no data were available on the work histories after the x-ray examinations occurred. A previous mortality study included 5 579 male production workers who registered for the two examinations.16 In the present study, the population was supplemented with 482 managerial persoris and with 84 persons who were not included in the original register (they had been invited to the earlier examinations but did not participate). Also, a few persons in the original register did not participate. Therefore, the present study included 6 054 male participants, and 91 male nonparticipants (1 of whom is excluded from analysis; see Table 1). Follow-up for death and emigration. Personal identification numbers were introduced in Denmark on 1 April 1968.17Therefore, the majority of cohort members had personal identification numbers, and they were followed up for deaths and emigrations by linkage with the Central Population Register. The few cohort members without personal identification numbers were all traced manually through the municipality population registers. Registration of cancer cases. A population-based cancer registration commenced in Denmark in 1943, and all patients who were living as of 1 April 1968 were registered with personal identification numbers. For cohort members with identification numbers, notified cancer cases were identified by linkage with the Cancer Register. For cohort members without identification numbers, notified cancer cases were identified by manual check of lists of cancer patients of equivalent sex and date of birth. Cancer cases notified between 1943 and 1977 were coded according to a modified version of the seventh revision of the International Classification of Diseases, ICD-7.’’ Cancer cases notified from 1978 to the present were coded according to the International Classification of Diseases for Oncology, ICD0.’’ Both classifications could distinguish the main histological types of lung cancer. Calculation of expected number of cancer cases. For each individual person years at risk were calculated using the date of the first x-ray examination in which the person participated. Fictive dates of x-ray examination were given to nonparticipants: 1 July 1967 was used for the first survey, and 1 January 1973 was used for the second survey. Person years at risk were calculated un. ti1 death, emigration, or end of follow-up on 31 December 1985. All tumors that were diagnosed during the individual risk periods were included in the analyses. Among the cohort of 6 144 mates, 647 tumors were identified, of which 532 were first tumors and 115 were second (or subsequent) tumors. Expected numtars were based on cancer incidence rates for the Danish population for sex, 5-y age groups, 76
and the following calendar periods: 1963-1967, 19681972, 1973-1 977, 1978-1 982, and 1983-1 985. The PYRS program was used for calculation of expected numbers.” Standardized morbidity ratios (SMRs) were calculated by dividing the observed number of cancer cases (obs.) by the expected number (exp.). Ninety-five percent two-tailed confidence intervals (95% CI) were calculated based on the assumptions that the observed number of cases followed a Poisson distribution,2’ and that for observed numbers over 30, a normal distribution would result.22 Results
Overall results of cancer incidence among the foundry workers are presented in Table 2, Only SMRs for all malignant neoplasms (SMR, 1.09; 95% CI, 1.01-1.18) and for lung cancer (SMR, 1.30; 95% CI, 1.12-1.51) were statistically significantly elevated. The SMR for bladder cancer was elevated at the borderline of statistical significance (SMR, 1.24, 95% CI, 0.97-1.59). The cancer risk was particularly elevated for the small group of 90 foundry workers who did not participate in the x-ray examination (Table 3). Table 4 describes the lung and bladder cancer incidence according to accumulated length of employment in foundries upon entry into the follow-up period. A progressive increase in SMRs was observed as length of employment increased. Statistically significantly elevated risks, or risks at the borderline of statistical significance, were seen for both lung and bladder cancer among foundry workers who had been employed at least 20 y. Table 5 describes lung and bladder cancer incidence according to foundry job at the onset of the follow-up period. A statistically significant excess risk for lung cancer was found for workers from metal foundries (SMR, 2.13; 95% CI, 1.19-3.52). A borderline significant excess for lung cancer was found for workers who were employed in iron and steel foundries (SMR, 1.21; 95% CI, 0.98-1.50). Bladder cancer incidence was significantly elevated among workers with unspecified jobs in iron foundries (SMR, 2.83; 95% CI, 1.14-5.84). Lung cancer incidence among foundry workers with and without silicosis at the time of entry into the followup period is shown in Table 6 . Silicotics and nonparticipants had the highest SMRs: 1.71 and 2.66, respectively. Because these groups are relatively small, none
Table 1.-Number of Male Foundry Workers Invited to the 1967-1969 and 1972-1974 X-Ray Examinations in Denmark X-ray examination
Participants Nonparticipants Analyzed data set
1967-1969
1972-1974
Total
3 959 49 4008
3 839 70
6 054
3909
91 * 6 145*
*One person was dead before fictive date of x-ray examination and was not included in the analyses.
Archives of Environmental Health
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Table 2.-Obserwd and Expected Number of Cancer Cases in Male Foundry Workers in Denmark 1967-1985 (No latency Period) ICD-7
Cancer
ObS.
Exp.
SMR
140-205 140 141 142 143-144 145-148 150 151 152 153 154 155.0 155.1 156 157 158-1 59 160 161 162.0,l 162.2 163 164 170 177 178 179
All malignant neoplasm Lip Tongue Salivary glands Mouth Pharynx @sop hagus Stomach Small intestine Colon Rectum Liver Gallbladder Liver (not primary) Pancreas Peritoneum Nasal cavities Larynx Lung Pleura Lung (not primary) Mediastinum Breast Prostate Testis Other and unspecified genital organs Kidney Bladder Melanoma of skin Other skin Eye Brain Thyroid Endocrinal glands Bone Connective tissue Metastates Other and unspecified sites Non-Hodgkin lymphoma Hodgkin’s disease Multiple myeloma Leukemia Mycosis fungoides
647 11 4 1 4 6 6 34 2 37 30 7 4 4 18 1 1 16 166 1 2 2 2 50 9 1
594.41 8.28 1.57 1.29 3.10 4.00 6.93 29.61 1.83 39.54 33.57 6.52 4.20 2.36 20.03 1.50 1.70 11.11 127.84 2.59 0.92 0.50 1.00 50.45 8.25 2.13
1.09 1.33 2.54 0.77 1.29 1.50 0.87 1.15 1.09 0.94 0.89 1.07 0.95 1.69 0.90 0.67 0.59 1.44 1.30 0.39 2.17 4.01 2.00 0.99 1.09 0.47
1.010.660.690.020.350.550.320.820.130.680.600.430.26-
18 63 9 65 2 13 3
0.91 1.24 0.90 0.93 1.18 0.85 1.71
0.540.970.410.730.140.450.35-
1.43 1.59 1.71 1.19 4.27 1.45 5.01
1 1 8 5
19.86 50.93 9.98 69.86 1.69 15.36 1.75 0.87 0.93 1.91 8.71 4.77
1.08 0.52 0.92 1.05
0.030.010.400.34-
5.99 2.92 1.81 2.45
11 7 4 17 1
11.34 3.79 6.23 15.18 0.42
0.97 1.85 0.64 1.12 2.40
0.48- 1.74 0.74- 3.80 0.18- 1.64 0.65- 1.79 0.06-13.26
180 181 190 191 192 193 194 195 196 197 198 199 200, 202 201 203 204 205
0
95% CI 1.18 2.38 6.52 4.32 3.30 3.27 1.88 1.61 3.95 1.30 1.28 2.21 2.44 0.46- 4.34 0.53- 1.42 0.02- 3.71 0.01- 3.28 0.82- 2.34 1.12- 1.51 0.01- 2.15 0.29- 7.85 0.48-14.44 0.24- 7.22 0.74- 1.31 0.55 2.07 0.01- 2.62
-
-
I
Table 3.-Observed and Expected Number of All Cancer and Lung and Bladder Cancer Cases in Male Foundry Workers, by Participation in X-ray Examination (No latency Time)
ICD-7
No. of persons
Obs.
Exp.
SMR
95% CI
6054 90
633 14
585.69 8.72
1.08 1.61
1.00-1.17 0.88-2.69
6054 90
161 5
125.96 1.88
1.28 2.66
1.10-1.49 0.86-6.21
6 054
62 1
50.17 0.76
1.24 1.32
0.97-1.59 0.03-7.33
t 140-205 162.0,l 181
March/AprillWl [Vol. 46 (No. 2)]
All malignant neoplasms Participants Nonparticipants Lung Participants Nonparticipants Bladder Participants Nonparticipants
90
Table 4.-Observtd and Expected Number of Lung Cancer Cases and Bladder Cancer Cases in Male Foundry Workers by Number of Years Accurnul,ited in Foundries at Date of X-ray Examination (No latency Period)
?
1
No. of
Lung cancer
Years in foundry
persons
Obs.
Less than 10 y 10-19 y 20-29 y 2 30 y Years not stated Nonparticipants
3 386 1127 900 613 28
All
1
Bladder cancer
EXP.
SMR
95% CI
Obs.
Exp.
SMR
95% CI
41.62 28.53 29.61 25.93 0.27 1.88
0.99 1.19 1.28 1.85
0.73-1.34 0.85-1.67 0.93-1.76 1.39-2.45
0.46-1.40 0.48-1.73 1.05-2.66 0.96-2.65
-
2.66
0.86-6.21
1
16.81 11.35 11.63 10.28 0.1 1 0.76
0.83 0.97 1.72 1.65
-
14 11 20 17 0
90
41 34 38 48 0 5
1.32
0.03-7.33
6 144
166
127.84
1.30
1.12-1.51
63
50.93
1.24
0.97-1.59
-
-
I I
I
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Table 5.-ObservixI and Expected Number of Lung Cancer Cases and Bladder Cancer Cases in Male Foundry Workers by Workplace in Foundries at Date of X-ray Examination (No Latency Period) No. of Years in foundry
I 1
Iron and steel foundry Foundry* Core room Finishing Unspecified Metal foundry Not foundry Workplace not stated Nonparticipants
All
Lung cancer
Bladder cancer
EXP.
SMR
95% CI
Obs.
Exp.
SMR
95% CI
85 13 28 9 15 11 0 5
70.22 9.91 24.37 6.18 7.03 8.00 0.26 1.88
1.21 1.31 1.15 1.46 2.13 1.37
0.98-1 .50 0.70-2.24 0.76-1.66 0.67-2.76 1.19-3.52 0.69-2.46
0.81-1.61 0.28-2.61 0.42-1.76 1.14-5.84 0.79-4.70 0.34-3.22
-
-
-
2.66
0.86-6.2 1
1
28.01 3.92 9.71 2.47 2.78 3.18 0.10 0.76
1.14 1.02 0.93 2.83 2.16 1.26
-
32 4 9 7 6 4 0
1.32
0.03-7.33
166
127.84
1.30
1.12-1.51
63
50.93
1.24
0.97-1.59
persons
Obs.
3 377 45 1 1 071 330 485 312 28 90 6 144
I
*Moulders, oven workers, casters, crane operators, and shake-out.
I
I
Table 6.-Observed and Expected Number of Cancer Cases in Male Foundry Workers, by Silicosis Diagnosis at X-ray Examination (No Latency Time) No. of persons
Participants Diagnosed with silicosis at x-ray examination Not diagnosed with silicosis Nonparticipants
All
Exp.
SMR
95% CI
144
11
6.43
1.71
0.85-3.06
5 910 90
150 5
119.53 1.88
1.25 2.66
1.07-1.47 0.86-6.21
6 144
166
127.84
1.30
1.12-1.51
of these risks was statistically significantly elevated. The large group of ncinsilicotics had a significantly elevated lung cancer risk (SMR, 1.25; 95% CI, 1.07-1.47). Iron and steel foundries were subdivided according to prevalence of silicosis per 1 OOO workers at the first x-ray examinatiori in 1967-1969. Table 7 shows an increasing incidence of lung cancer, which corresponds to increasing prevalence of silicosis. A significantly elevated risk was iiound among workers coming from foundries with 40-250 silicotics per 1 OOO (SMR, 1.40; 95% CI, 1.16-1.76). Lung cancer cases were divided into four histologic types. Excess lung cancer risk among the foundry work78
Obs.
ers came from both squamous cell carcinomas (SMR, 1.42; 95% CI, 1.13-1.791, anaplastic carcinomas (SMR, 1.30; 95% CI 0.96-1.761, and other lung cancers (SMR, 1.28; 95% CI 0.89-1.781, whereas the number of adenocarcinomas was close to the expected number for all Danish men (SMR, 1.04; 95% CI 0.64-1.65).
Discussion The present study showed a moderately increased risk of lung cancer among foundry workers in Denmark (SMR, 1.30; 95% CI, 1.12-1.51). This excess risk is slightly lower than that found for foundry workers in Archives of Environmental Health
Table 7.-Observed and Expected Number of Lung Cancer Cases in Male Foundry Workers by Prevalence of Silicosis in the Company at the First X-ray Examination (No latency Time)
No. of persons
Obs.
Exp.
SMR
95X CI
24.24 39.39 53.67 7.03
0.60-1.42 0.89-1.58 1.16-1.76 1.19-3.52 0.02-3.40 0.86-6.21 1.12-1.51
t Iron and steel foundries 0 silicoticsll OOO 1-39 silicoticsll OOO 40-250 silicotics/l OOO Metal foundries Others Nonparticipants
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I
1468
1 820 2 174 485 107 90
All
6 144
Table 8.-Observed and Expected lung Cancer Cases in Male Foundry Workers by Histology (No latency Time)
Histology Squamous cell carcinomat Adenocarcinoma Anaplastic carcinoma All others Total
71
50.16
1.42
18 42 35
17.29 32.37 27.42
1.04 0.62-1.65 1.30 0.96-1.76 1.28 0.89-1.78
166
127.24
1.30
1.13-1.79
1.12-1.51
*The standard rates used in this calculation were based on a later version of the cancer register than those used in the other tables. Therefore, the expected number of lung cancers is 127.24 in this table, but is 127.84 in the other tables. tlncludes “solid carcinoma, NOS.”
other countries where the risk estimates have normally been in the range of 1.5-2.5.’-” The Danish study is based on cancer incidence data, whereas the previous studies have been based on mortality data. With respect to lung cancer, however, this should not distort the comparison between foundry workers and the respective national populations. The Danish study population was collected from nationwide surveys where all workplaces were included independently of the work environment. Good tracing possibilities in Denmark insured that all invited foundry workers were traced successfully and followed up. However, only an average of 15 y had elapsed between x-ray examinations and the end of the follow-up period. More than half of the workers reported that they had worked in the foundries for less than 10 y. Lung cancer risk increased with number of years accumulated in foundry work upon entry into the followup period. The risk for workers who had less than 10 y employment was similar to that of all Danish men (SMR, 0.99; 95% CI, 0.73-1.341, and risk increased almost twofold for workers who had been employed for at least 30 y (SMR, 1.85; 95% CI, 1.39-2.45). Concomitant increases in lung cancer risk and in duration of employment in foundries has also been observed in the United Kingdomg and Poland.” In the present March/Aprill991 [Vol. 46 (No. Z)]
23 47 75 1 5
1.64
1.88
0.95 1.19 1.40 2.13 0.61 2.66
166
127.84
1.30
15
study, the cohort was constructed from cross-sectional data. Regardless of date of employment, only those workers who remained in their foundry jobs until the x-ray examinations took place were included in the present study. Therefore, analysis of the data by time since first employment is not meaningful. When the cohort members were divided according to work tasks at the time of the x-ray examination, only the small subgroup of workers from the metal foundries had a significantly elevated lung cancer risk (SMR, 2.13; 95% CI, 1.19-3.52). There were only slight differences in the lung cancer risk between the four groups of workers from the iron and steel foundries. Previous studies have pointed to finishing” or fettling workg and furnace workg as being the jobs in iron foundries with the highest lung cancer risk. However, this pattern was not seen among Danish foundry workers. A possible explanation may be that many of the workplaces were small, and workers often helped each other at different jobs. Therefore, no attempt was made to divide the foundry workers into categories according to levels of potential workplace exposures, e.g., based on measurements recorded in the literature. Furthermore, there was an association between job title and length of employment. Core makers and hand moulders were skilled workers who had long seniority in their trade, whereas finishing workers were unskilled workers and normally had short seniority. The etiology for the increased lung cancer risk among long-term foundry workers is uncertain because foundry workers are exposed to many chemical compounds.” The availability of x-ray examinations allowed us to look further into the relationship between silica exposure and lung cancer. The highest lung cancer risk was found among workers who were diagnosed with silicosis at the x-ray examinations (SMR 1.71) and among workers who did not participate for various reasons, including illness (SMR 2.66). The cases in these groups, however, comprised only 16 of 166 observed lung cancer cases, and there was a significant, moderately increased lung cancer risk (SMR, 1.25; 95% CI, 1.07-1.47) among the majority of workers without silicosis at the start of the 15-y follow-up period. Furthermore, a trend existed where workers from foundries where there were no cases of 79
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silicosis had a lung cancer risk similar to that of all Danish men SMF: (0.951,whereas workers from foundries where there was a high prevalence of silicosis had 95% significantly elevated lung cancer risk, (SMR, 1.a; CI, 1.16-1.76). The concomitant increase in SMRs for lung cancer with increasing silicosis prevalence suggests a dose-response relationship between lung cancer and silica exposure. When interpreting these results, it should be remembered that the presence of silicosis was known only upon entry into the follow-up period. Furthermore, a high prevalence of silicosis might indicate a generally poor work environment, including exposure to other potentially carcinogenic substances. The diagnosis was based on a full-sized chest x-ray interpreted by the same expert using the International Labor Organization‘s Classification of Pneumoconiosis from 1958.13-14However, a minor degree of misclassification cannot be excluded, and a normal x-ray does not completely exclude the presence of silica-induced pulmonary fibro~is.’~ There has been considerable interest in polycyclic aromatic hydrocarbons (PAHs) (e.g., benzo(a)pyrene) as possible causative factors for the excess lung cancer risk that exists among foundry workers. Air particulates in foundry air can be mutagenic.24Benzo(a)pyrene adducts have been detected in blood samples from foundry workers, and there may be a dose-response relationship between adduct level and environmental contamirtati~n.’~,’~ Also, there is experimental evidence that higher intracellular levels of benzo(a)pyrene can be achieved when there is simultaneous exposure to silica particle^.^' Our data do not allow an analysis of the lung cancer risk according to level of PAH exposure. Exposure to nickel and chromium may occur in the metal foundries, and the significantly increased lung cancer risk among workers from the metal foundries may reflect exposure to those metals. Many attempts have been made to correlate histologic subtypes oi lung cancer with oc~upation.’~-~’ These studies are difficult because tobacco consumption is related to all major cell types.30 There are, however, some suggestions of occupationally related correlations. Small-cell carcinomas appear to be related to bischloromethyl ether and uranium exposure. Adenocarcinomas are often seen in connection with asbest,os exposure. Evidence exists that squamous cell carcinomas may be related to chromate, nickel, and PAH e~posure.’~,~’ The histology data may vary, however, depending on the use of different classification systems and the specimen source. The interobserver variability may be as high as 42°/0.28 Our data show that the excess lung cancer risk among foundry workers results from squamous cell carcinomas, anaplastic carcinomas, and the residual group of other cancers. The foundry workers’ risk for adenocarcinomas of the lung was equivalent to that of all Danish men. It is unlikely that bias as a result of specimen source or interobserver variability would invalidate these data because any bias would probably be consistent across the Danish population. 80
The fact that both lung and bladder cancer risks were increased among the foundry workers could raise suspicion to confounding from tobacco smoking. There were, however, only minor differences in the smoking pattern across socioeconomic groups in Denmark around 1970,32and the fact that both the increased lung and bladder cancer risks were confined to longterm workers points to an occupational etiology. The mortality from bladder cancer has been reported in only four of the previous studies on foundry workers. A slight excess risk of bladder cancer was indicated in three studies from the United state^,^,^^'^ but not in a study from the United K i n g d ~ m The . ~ excess bladder cancer risk in Denmark was seen only for long-term foundry workers, and the results for entire cohorts will probably depend on the composition of the cohorts according to length of employment. There was no association between foundry work and bladder cancer in the U.S. National Bladder Cancer Study in which foundry work was considered if the job was held for at least 6 mo and smoking was controlled for in the analysis.”,” Exposure to aromatic amines formed from the binders is a possible explanation for the excess bladder cancer risk in long-term foundry workers. In conclusion, the present study demonstrated increased lung and bladder cancer incidence among long-term foundry workers in Denmark. The data suggest a dose-response relationship between silica exposure and lung cancer incidence. Excess lung cancer risk was confined to squamous cell carcinomas, anaplastic carcinomas, and other lung cancers, whereas there was no excess risk from adenocarcinomas of the Iung.
********** Submitted for publication March 22, 1990; revised; accepted for publication October 1, 1990. Requests for reprints should be sent to: David Sherson, Dept. of Occupational Medicine, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark.
********** References
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