American Journal of Industrial Medicine 18:69-78 (1990)
Occupational Risk Factors for Gastric Cancer in Shanghai, China Robert W. Kneller, MD, MPH, Yu-Tang Gao, MD, Joseph K. McLaughlin, PhD, Ru-Nie Gao, MD, William J. Blot, PhD, Ming-Hao Liu, BS, Ji-Ping Sheng, BS, and Joseph F. Fraumeni, Jr., MD
Occupational data for over 13,000 incident stomach cancer cases reported to the Shang hai Cancer Registry between 1980 and 1984 were compared with 1982 census employ ment information to calculate standardized incidence ratios for stomach cancer in the Shanghai urban area. Several occupations were found to have statistically significantly increased risks for stomach cancer, most notably grain farming and several jobs involv ing potential for exposure to metal, wood, and other dusts and to fossil fuel combustion products. Because of the large numbers involved and consistency of associations, the findings raise hypotheses regarding occupational exposures that warrant further inves tigation. Key words: gastric cancer epidemiology, grain farming, dust, metal working, fossil fuel combus tion products
INTRODUCTION Stomach cancer is the leading cause of cancer mortality in China [Li et al., 1981] and one of the most common cancers worldwide [Page and Asire, 1985], even though its incidence has been declining steadily in the United States [Devesa et al., 1987] and many other industrialized countries. Its causes are poorly understood. Dietary factors are thought to be paramount [Nomura, 1982; Davies, 1981 ; You et al., 1988], but although the role of occupational exposures is not well established, in creased risks for stomach cancer have been found in a number of occupations, including work in the rubber [Sorahan et al., 1986; IARC Monograph, 1982], oil refining [Thomas et al., 1984; Hanis et al., 1979], ball bearing [Park et al., 1988], and jewelry [Dubrow and Gute, 1987; Sparks and Wegman, 1980] industries and in occupations involving high levels of exposure to dust [Wright et al., 1988] and asbestos [Miller, 1978; Clemmesen and Hjalgrim-Jensen, 1981; Newhouse et al., Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD (R.W.K., J.K.M., W.J.B., J.F.F. Jr.). Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (Y.-T.G., R.-N.G.). Census department, Shanghai Institute of Applied Statistics, Shanghai, China (M.-H.L., J.-P.S.). Address reprint requests to Dr. Kneller, NCI/NIH, Executive Plaza North, Rm 432, Bethesda, MD 20892. In China address reprint requests to Dr. Y.-T. Gao, Dept. of Epidemiology, Shanghai Cancer Institute, 2200 Xie-Tu Rd., Shanghai, 20032, China. Accepted for publication January 4, 1990. © 1990 Wiley-Liss, Inc.
70
Kneller et al.
1988]. The present study analyzes stomach cancer risk by occupation using cancer incidence data for Shanghai, the largest industrial city in China, and employment information from census data. The primary purpose of this analysis is to generate and refine hypotheses regarding occupational risks for stomach cancer. MATERIALS AND METHODS Occupational data from the Shanghai Cancer Registry on incident cancer cases diagnosed between 1980 and 1984 in urban residents aged 30 years and over were compared with population data on occupation from the 1982 census. At the time these data were collected, the Municipality of Shanghai consisted of 11 urban administrative districts and ten rural counties. According to the latest Shang hai census, completed as part of the Third National Census, the population of the urban districts was 6.3 million, while the population of the rural counties was 5.5 million as of July 1, 1982 [Office of the Shanghai Population Census, 1985]. This report focuses on ten of the 11 urban districts, which henceforth are referred to as "urban Shanghai." One small outlying urban district was excluded from the analysis. There were 1.57 million men and 1.55 million women aged 30 years and over who resided in urban Shanghai [Office of the Shanghai Population Census, 1985]. Infor mation on their occupations was included in the census registration form and coded, using standardized nomenclature [National Bureau of Statistics (China), 1982]. Then, tabulations by sex and 5-year age groups were made of numbers of workers in each of eight broad single-digit, 64 general two-digit, and 301 specific three-digit occu pational categories. The census identified 842,735 retired persons. Using a 10% systematic sample of household groups (i.e., units of 10-15 households) 87,485 of these persons were selected for follow-up interviews [Gao et al., in press]. Occupation at time of retire ment was successfully collected on 95.1% of the sample (83,202 persons) and used to estimate the occupational distribution of all retired persons at the time of retirement by age and sex. This enabled us to assign occupational classifications to the entire urban population aged 30 years and over at the time of the census. The Shanghai Cancer Registry has collected cancer incidence and mortality data for the ten urban districts of Shanghai since 1963, except for the years 1966 to 1971 [Muir et al., 1987]. It is one of the contributors to Cancer Incidence in Five Continents published by the International Agency for Research on Cancer [Muir et al., 1987], and the methods and procedures used in the Registry are described therein and elsewhere [Gao, 1984]. After deleting from the Registry those cases whose residence was outside of urban Shanghai, there were 65,474 incident cancer cases among persons aged 30 years and over during the period 1980-1984. Of these cases, 13,489 (21%) were gastric cancers; 9,132 (68%) of these cases were males and 4,357 (32%) were females. Occupation at time of cancer diagnosis or time of retirement was ascertained for 98% of the gastric cancer patients by interviewing either the patients (19.7%) or their next of kin or work supervisors (80.3%). Occupation nomenclature and coding were the same as used in the census [Gao et al., in press]. In order to determine whether occupational data obtained for the cancer cases by our interviews were consistent with employment information obtained by the census, a comparison of occupational classifications by the two methods was made for a random sample of 306 male and 104 female non-retired cancer cases. The one-digit
Occupational Gastric Cancer Risks in Shanghai
71
TABLE I. Standardized Incidence Ratios (SIRs) for Stomach Cancer, by Broad (1-Digit) Occupational Categories, Among Men in Urban Shanghai, 1980-1984 Code
Occupation
No. cases
SIR
6 7,8,9 3 5 4 0,1 2
Agricultural workers Production and transport workers Clerical workers Service workers Commercial (sales) workers Professionals Government officials
124 4,658 478 1,424 750 904 452
159a 109a 104 102 93 71 a 70 a
'p< .01. census occupational classifications for these individuals were the same for 95% of the males and 96% of the females. Concordance at the two-digit level was 90.5% and 91.3% and at the three-digit level 86.6% and 85.6% for males and females, respec tively [Gao et al., in press]. These concordance rates are similar to rates found in linked registry data sets in Scandinavian countries [Malker, 1988]. Age-, sex-, and site-specific cancer incidence rates for urban Shanghai were calculated for 1980-1984. These citywide incidence rates were then applied to the census-derived age- and sex-specific estimates of the number of residents in each occupational category to calculate the expected number of cancer cases in each group. The observed number of cases in each occupation was divided by the expected number of cases and multiplied by 100 to obtain standardized incidence ratios (SIRs). This method of indirect adjustment was used because of the instability of incidence rates in certain occupational categories due to the small numbers of cases in these categories. Statistical significance was tested assuming that the observed numbers of cancer cases followed a Poisson distribution [Bailar and Ederer, 1964]. RESULTS At the broad, one-digit level, male agricultural workers and production and transportation workers had significantly elevated risks for stomach cancer (Table I). In contrast, professionals and government workers had significantly low risks. Fe male agricultural workers also had a significantly increased risk for stomach cancer (SIR = 187, 44 cases, p < .01). Table II lists the two-digit occupational categories with significantly high risks of stomach cancer in men and the three-digit occupational categories therein. At the two-digit level, farmers had a greater than twofold risk, while administrative clerks, public service workers, leather/fur processors, wood workers, transport workers, freight handlers/moving equipment operators, and metal workers (except those in refining and primary metal processing) had significantly elevated risks, though these were within 40% of expected values. At the three-digit level, grain farmers had the most striking excess risk (fourfold), with 89 cases. Risk for railway engine drivers/ firemen also was close to four times higher than expected. A potential for heavy dust exposure, especially wood or metal dust, characterized several of the high-risk oc cupational groups, including wood sawyers and plywood workers, cabinetmakers, precision instrument makers, blacksmiths, and metal grinders.
TABLE II. Statistically Significant Standardized Incidence Ratios (SIRs) for Stomach Cancer, by General (2-Digit) Occupational Categories, With Specific (3-Digit) Occupations, Among Men in Urban Shanghai, 1980-1984 Code
Occupation
3.1 Administrative clerks 3.11 Government and business clerks 3.12 Secretaries 3.19 Other clerical workers Other 3-digit categories combined for convenience 5.1/5.2 Public service workers 5.11 Waiters 5.12 Hotel and restaurant personnel 5.15 Transportation attendants for buses, trains, and boats 5.16 Ticket takers for trains, theaters, and public baths 5.21 Fuel suppliers 5.22 Sanitation personnel, street cleaners, and garbage men 5.23 Misc. workers (doormen, messengers, janitors, etc.) 5.29 Other public service workers Other 3-digit categories combined for convenience 6.1 Farmers 6.11 Grain farmers 6.13 Vegetable farmers 6.14 Tea, vineyard, and orchard farmers 6.19 Other farmers 7.6 Leather and fur processors 7.61 Tanners, feltmongers, and pelt dressers 7.62 Leather products workers 8.0 Wood preparation workers, cabinetmakers and bamboo, hemp, rattan, and straw product makers 8.02 Wood sawyers, plywood makers, and related wood-processing workers 8.03 Cabinetmakers 8.04 Construction carpenters 8.09 Other wood and bamboo workers Other 3-digit categories combined for convenience 8.4 Blacksmiths, toolmakers, and machine-tool operators 8.41 Blacksmiths, hammersmiths, and forging-press operators 8.42 Toolmakers, metal patternmakers, and metal workers 8.43 Machine-tool setters 8.44 Metal grinders, polishers, tool sharpeners, and machine-tool operators 8.49 Other blacksmiths, toolmakers, and machine-tool operators 8.5 Machinery fitters, machine assemblers, and precision instrument makers (except electrical) 8.51 Machinery fitters and machine assemblers 8.52 Machinery, motor vehicle, and aircraft engine mechanics 8.53 Watch, clock, and precision instrument makers 8.59 Other machinery fitters, assemblers, and precision instrument makers 8.8 Plumbers, welders, and sheet metal and structural metal preparers and erectors 8.81 Plumbers and pipe fitters 8.82 Welders and flame cutters 8.83 Sheet-metal workers 8.84 Structural metal preparers and erectors
Cases
SIR
370 59 17 283 11
IIIa
1,153
107 32 25 51 23 66 757 22 14 104 89 12 1 2 60 5 55
36 104 211"
67 110b 134a
117 162a 150a
133 157b 109a
70 81 232" 402"
92 203 22a 133a
94 150a
280 25 36 84 127 8 474
176a 147a
42 193 3
156b
111 305
191
141b
45
79
293 31
119a
232 23
126b 172a
7
47a
190 17 38 133 2
127b
70b 195b
63 120"
91
111 119 140b
27a (continued)
Occupational Gastric Cancer Risks in Shanghai
73
TABLE II. Statistically Significant Standardized Incidence Ratios (SIRs) for Stomach Cancer, by General (2-Digit) Occupational Categories, With Specific (3-Digit) Occupations, Among Men in Urban Shanghai, 1980-1984 (continued) Code
Occupation
9.4 Material handling and related equipment operators, dockers, and freight handlers 9.41 Dockers and freight handlers 9.42 Crane and hoist operators 9.43 Earth-moving and related machinery operators 9.49 Other material handling equipment operators 9.5 Transportation equipment operators 9.51 Ships' deck ratings, barge crews, boatmen, and ships' engine-room ratings 9.52 Railway engine drivers and firemen 9.54 Automobile and truck drivers 9.57 Rickshaw and handcart drivers Other 3-digit categories combined for convenience a
Cases
SIR
612 558 51 2 1 485
139" 154b
130 14 153 151 37
81 22a 17a 123b
114 363"
115 153b
83
p < .05. p < .01.
b
Table III lists 11 other three-digit occupations with significantly elevated risks for men that are not included within the two-digit categories listed in Table II. SIRs for nurses, pesticide production workers, and petroleum refinery workers were more than four times greater than expected, although the numbers of cases were small. Laboratory technicians had a twofold excess risk. Excesses of nearly 50% were observed for metal smelting and metal rolling mill workers, boiler firemen, and textile machinery mechanics. Elevated risks for women paralleled those for men in several occupations: grain farmers (SIR = 414, 36 cases, p < .01); wood sawyers, plywood makers and related workers (SIR = 308, 9 cases, p < .01); machinery, motor vehicle, and aircraft engine mechanics (SIR = 231, 15 cases, p < .01); sanitation personnel, street cleaners, and garbage collectors (SIR = 193, 32 cases, p < .01); and rickshaw and handcart drivers (SIR = 172, 24 cases, p < .05). The only occupations with more than 5 female cases that had significantly elevated risks for women but not for men were plastic manufacturing and plastic products makers (41 cases, SIR = 160, p < .01), knitters (83 cases, SIR = 148, p < .01), and weavers (178 cases, SIR = 117, p < .05). DISCUSSION
The role of occupational exposures in stomach cancer remains unclear despite a variety of clues. With more than 13,000 cases of stomach cancer, the Shanghai occupation-cancer registry enabled us to look for occupational associations in a coun try where this issue has not been systematically evaluated. Our survey revealed several etiologic leads, some of which have been previously reported in other coun tries. Since there was close correspondence between occupational risks for men and women, we shall discuss only risk factors for men unless specifically noted.
74
Kneller et al. TABLE III. Statistically Significant Standardized Incidence Ratios (SIRs) for Stomach Cancer, by Specific (3-Digit) Occupations Not Included in Table II, Among Men in Urban Shanghai, 1980-1984 Code
Occupation
0.75 0.76 7.21
Nurses Laboratory technicians Metal smelting, converting, and refining furnacemen Metal rolling-mill workers Pesticide production workers Petroleum refinery workers Rubber manufacturing and rubber product makers (except tires) Textile machinery mechanics Bleachers, dryers, and textile product finishers Electricians (wiremen), electrical linemen, and cable joiners Boiler firemen
7.22 7.33 7.36 7.41 7.53 7.56 8.64 9.33 a
Cases
SIR
5 13
574 b 201 a
83 34 3 5
149b 147a 564 a 439 a
42 168 91
139a 147b 126a
123 118
124a 159"
p < .05. p < .01.
b
Prior studies have reported elevated stomach cancer risks among farmers as a group, with some investigators suggesting that high nitrate levels in drinking water may be involved [Blair et al., 1985]. In our study, the high SIR among farmers was entirely accounted for by a fourfold elevated risk of stomach cancer among grain farmers. This finding is consistent with a death certificate analysis of Iowa farmers, which found a geographic correlation between stomach cancer rates and yields of corn per acre by county [Burmeister et al., 1989], although a similar association was not found in Wisconsin [Saftlas et al., 1987]. While it is possible that the numbers of cases among Shanghai grain farmers may be inflated due to migration into the urban districts to seek medical care, any over-estimation is likely to be small because we excluded persons whose official residence was outside the ten urban survey districts, and it is very difficult for a rural dweller to change official residence to an urban district [Gao et al., in press]. Farmers account for 0.8% of the working population of urban Shanghai, most living in the peripheral urban districts [Gao et al, in press]. Due to contact with moldy grain, grain farmers may have greater exposure to fungal toxins such as aflatoxins, tricothecenes, or sterigmatocystin, which have been reported to cause gastric neoplasms in laboratory animals [Butler and Barnes, 1966; Ohtsubu and Saito, 1977; Purchase and Watt, 1970]. Grain farmers may also have greater exposure to fungicides. A case-control study of non-Hodgkin's lymphoma in Kansas, a major wheat-producing state, found that cases were more likely than controls to have treated seeds with fungicides [Hoar et al., 1986]. To our knowledge, however, there have been no reports linking stomach cancer in grain or other farmers to use of fungicides, insecticides, or herbicides. It is noteworthy that Shanghai pesticide production work ers had an SIR more than five times greater than expected (Table III); however, Shanghai grain millers and oil pressmen showed no excess risk. Several other occupational associations identified in Shanghai are consistent with surveys from other countries. The increased stomach cancer risks we observed among metal grinders/polishers and machinery mechanics are consistent with pub-
Occupational Gastric Cancer Risks in Shanghai
75
lished reports [Park et al., 1988; Jarvholm et al., 1982; Dubrow and Wegman, 1984; Walrath et al., 1985; Bross et al., 1978] and may possibly result from exposure to lubricating oils, to N-nitroso or anti-rust compounds contained in lubricating oils, or to polishing compounds [Park et al., 1988; Jarvholm et al., 1982]. One study among grinders revealed rising urinary nitrosamine levels as the work week progressed [Spiegelhaider et al., 1987]. In addition, our findings of elevated risk among rubber and oil refinery workers have been noted elsewhere [Sorahan et al., 1986; IARC Monograph, 1982; Thomas et al., 1982, 1984; Hanis et al., 1979], as have the high risks we observed among several woodworking occupations (cabinetmakers, wood sawyers/plywood makers, and other wood workers) [Dubrow and Wegman, 1984; Walrath et al., 1985; Milham, 1983; Petersen and Milham, 1980]. In Shanghai, the increased risk among leather product workers (excluding tanners and shoemakers) is similar to findings in a Massachusetts survey [Dubrow and Wegman, 1984], while the elevated risk among railway engine drivers/firemen resembles the observations for locomotive engineers among U.S. veterans [Walrath et al., 1985]. Finally, the in creased risk among female plastic workers is interesting in view of similar findings in Massachusetts [Dubrow and Wegman, 1984]. These results point to exposure categories that may warrant further examination. First, elevated risks were found for a number of dust-exposed occupations, including those with high levels of metal, wood, and textile dust exposure. The elevated risks of stomach cancer among foundry workers [Fletcher, 1986], cement workers [McDowall, 1984], coal miners [Bridbord et al., 1979], textile machinery operators [Bross et al., 1978], and workers in other dusty occupations [Bross et al., 1978; Neuberger et al., 1986] have suggested that heavy dust exposure may be a risk factor for gastric cancer. Long-term exposure to asbestos fiber dust has been associated with an increased risk of gastric and other digestive tract tumors [Miller, 1978]. However, there has been little evidence of a dose-response relationship for dust-related occu pations, and some studies have shown no evidence of increased risk [Swaen et al., 1987; Amandus, 1986]. Also, it has been hard to disentangle confounding variables such as smoking and socioeconomic status [Creagan et al., 1974]. One study sug gested that the increased risk associated with coal dust exposure is limited to miners who smoke cigarettes [Ames, 1983]. A recent Los Angeles study found an associa tion between stomach cancer incidence and occupational dust exposure (proportional incidence ratio [PIR] = 1.3, 95% CI = 1.2—1.4), even after adjusting for ethnic background and immigrant and socioeconomic status, although cigarette smoking was not controlled for [Wright et al., 1988]. In those parts of the stomach most likely to develop cancer, the antrum and pylorus, slightly higher risks were observed for heavy versus moderate dust exposure. Based on these findings, it was suggested that reductions in occupational dust exposure may have contributed to the declining stom ach cancer incidence in the United States [Wright et al., 1988]. Second, we found that stomach cancer risks were elevated among workers in high-temperature environments near open fossil-fuel combustion sources (e.g., rail way engine drivers, boiler firemen, blacksmiths, metal rolling-mill workers, and metal smelting/refining furnacemen). This observation is consistent with the excess stomach cancer risks reported among nickel [Haas and Schottenfeld, 1978] and steel [Fletcher, 1988] refinery workers and roofers [Hammond et al., 1976], although the findings for coke oven workers [Redmond et al., 1976] and coal gas workers [Doll et al., 1972] have been unremarkable. In Shanghai, further studies are needed to de-
76
Kneller et al.
termine exposure levels among these workers to polyaromatic hydrocarbons, Nnitroso compounds, asbestos, and other agents. Because the risk of stomach cancer is correlated with low socioeconomic status in various countries [Logan, 1982], it is possible that social class differentials con tributed to the low risks observed for professional and government jobs and the elevated risks for several blue-collar occupations. In a rural area of China, stomach cancer cases were 30% more likely than randomly selected controls to be from low-income rather than high-income households [You et al., 1988]. Similar socioeconomic gradients were seen in Japan, where stomach cancer incidence rates are equivalent to those in China [Muir et al., 1987; Hirayama, 1971], although stronger socioeconomic effects have been reported in Great Britain [Logan, 1982]. Several factors, however, suggest that socioeconomic gradients are not the sole explanation for the high-risk occupations identified in this survey. The SIRs observed for Shanghai grain farmers, metal workers, wood workers, leather products workers, petroleum refinery workers, dust-exposed workers, workers exposed to high-temperature combustion products, and female plastics workers and knitters appear too high to be accounted for even by fairly strong social class confounding [Logan, 1982; Hirayama, 1971]. Furthermore, the relatively equal distribution of income and social benefits, such as free medical care and highly subsidized housing in Shanghai since the 1950s, should have tended to reduce dif ferentials in risk factors related to socioeconomic status among workers. Moreover, during the period of the study, the ratios of highest to lowest quantiles of income within occupational groups and the ratios of average incomes between occupational groups did not exceed two in Shanghai (Shanghai Bureau of Statistics: Personal Communi cation). Lifestyle differences that may be linked to both socioeconomic factors and gastric cancer, however, cannot be ruled out. Several other caveats should be remembered when interpreting these data. The classification of occupations provides no direct information on actual exposure. In addition, no data are available on other risk factors for gastric cancer whose frequency may differ among occupational groups, most notably dietary habits and perhaps cigarette smoking [Nomura, 1982; You et al., 1988]. The problem of multiple com parisons must be acknowledged, since a large number of employment categories were examined, and some may have achieved statistical significance by chance alone. We have not performed statistical adjustments for this, since the study is hypothesisgenerating in nature. We intend, however, to launch analytical studies focusing on occupational exposures suggested in this survey. Finally, no data are available on duration of occupation, although job changes are typically less frequent in Shanghai than in urban areas of Western countries. Based upon responses to interviews ad ministered to all the cancer cases and to 10% of all the retirees in Shanghai, less than 8% of persons in the one-digit categories that contained most of the high-risk occu pations changed jobs within 5 years of retirement [Gao et al., in press]. Despite the generic limitations of this survey, the findings from this large data base should help to generate and refine etiologic leads and to set priorities for ana lytical studies aimed at evaluating occupational and environmental determinants of stomach cancer.
REFERENCES Amandus HE (1986): Mortality from stomach cancer in United States cement plant and quarry workers, 1950-80. Br J Ind Med 43:526-528.
Occupational Gastric Cancer Risks in Shanghai
77
Ames RG (1983): Gastric cancer and coal mine dust exposure. A case-control study. Cancer 52:13461350. Bailar JL, Ederer F (1964): Significance factors for the ratio of a Poisson variable to its expectation. Biometrics 20:639-643. Blair A, Malker H, Cantor KP, Burmeister L, Wiklund K (1985): Cancer among fanners: A review. Scand J Work Environ Health 11:397-407. Bridbord K, Costello J, Gamble, Groce D, Hutchison M, Jones W, Merchant J, Ortmeyer C, Reger R, Wagner WL (1979): Occupational safety and health implications of increased coal utilization. Environ Health Perspect 33:285-302. Bross ID, Viadana E, Houten L (1978): Occupational cancer in men exposed to dust and other environ mental hazards. Arch Environ Health 32:3000-3007. Burmeister LF, Everett GD, Van Lier SF, Isacson P (1989): Selected cancer morality and farm practices in Iowa. Am J Epidemiol 118:72-77. Butler WH, Barnes JM (1966): Carcinoma of the glandular stomach in rats given diets containing aflatoxin. Nature 209:90. Clemmesen J, Hjalgrim-Jensen S (1981): Cancer incidence among 5686 asbestos-cement workers fol lowed from 1943 through 1976. Ecotoxicol Environ Safety 5:15-23. Creagan ET, Hoover RN, Fraumeni JF (1974): Mortality from stomach cancer in coal mining regions. Arch Environ Health 28:28-30. Davies JM (1981): Mortality trends for stomach cancer in England and Wales. Br J Cancer 44:879-885. Devesa SS, Silverman DT, Young JL, Pollack ES, Brown CC, Horn JW, Percy CL, Myers MH, McKay FW, Fraumeni JF (1987): Cancer incidence and mortality trends among whites in the United States, 1947-84. JNCI 79:701-707. Doll R, Vessey MP, Beasley RWR (1972): Mortality of gas workers. Final report of a prospective study. Br J Ind Med 29:394-406. Dubrow R, Wegman DH (1984): "Occupational Characteristics of Cancer Victims in Massachusetts: 1971-1973." Cincinnati: DHHS (NIOSH) Publication No. 84-109, pp 65,89,91,94,96. Dubrow R, Gute DM (1987): Cause-specific mortality among Rhode Island jewelry workers. Am J Ind Med 12:579-593. Fletcher AC (1986): The mortality of foundry workers in the United Kingdom, In Goldsmith DF, Winn DM, Shy CM (eds): "Silica, Silicosis, and Cancer: Controvery in Occupational Medicine." New York: Praeger, pp 385-401. Fletcher AC (1988): The mortality of steel foundry workers: A cohort study. Diss Abstr Int [B] 49:85 (full text available from University Microfilms International, An Arbor, MI, as order no. AADDX80355). Gao Yu-Tang (1984): Cancer incidence in Shanghai during 1973-77. Nati Cancer Inst Monogr 62:43-46. Gao YT, McLaughlin JK, Gao RN, Kneller RW, Liu MH, SHeng JP, Blot WJ (1990): Investigation of occupational cancer incidence in Shanghai: Background and methods. Shanghai Tumor (in press). Haas JF, Schottenfeld D (1978): Epidemiology of gastric cancer. In Lipkin M, Good RA (eds): "Gas trointestinal Tract Cancer." New York: Plenum, pp 173-206. Hammond EC, Selikoff IJ, LawtherPL, Seidman H (1976): Inhalation of benzopyrene and cancer in man. Ann NY Acad Sei 271:116-124. Hanis NM, Stavraky KM, Fowler JL (1979): Cancer mortality in oil refinery workers. J Occup Med 21:167-174. Page HS, Asiré AJ (1985): "Cancer Rates and Risks," 3d ed. (NIH Publication No. 85-691), U.S. Department of Health and Human Services. Hirayama T (1971): Epidemiology of stomach cancer. Gann Monogr Cancer Res 11:3-19. Hoar SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Fraumeni JF, Jr (1986): Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 256:1141-1147. International Agency for Research on Cancer (1982): "Monograph on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Vol. 28. The Rubber Industry." Lyon: IARC. Jarvholm B, Thiringer G, Axelson O (1982): Cancer morbidity among polishers. Br J Ind Med 39: 196,197. Li JY, Liu BQ, Chen ZJ, Sun XD, Rong SD (1981): Atlas of cancer mortality in the People's Republic of China. Int. J. Epidemiol. 10:127-133. Logan WP (1982): "Cancer Mortality by Occupation and Social Class 1851-1971." London: Her Majesty's Stationery Office.
78
Kneller et al.
Malker HSR (1988): Register-epidemiology in the identification of cancer risks. Arbete Och Halsa 21:7-50. McDowall ME (1984): A mortality study of cement workers. Br J Ind Med 41:179-182. Milham S, Jr (1983): "Occupational Mortality in Washington State: 1950-1979." Cincinnati: DHHS (NIOSH) Pub. No. 83-116, p 1593. Miller AB (1978): Asbestos fibre dust in gastro-intestinal malignancies: Review of the literature with regard to a cause effect relationship. J Chronic Dis 31:23-33. MuirC, Waterhouse J, MackT, Powell J, Whelan S (eds) (1987): "Cancer Incidence in Five Continents: Vol V . " Lyon: IARC Scientific Pub. No. 88, pp 394-97. National Bureau of Statistics, General Administration of National Standards, Office of the National Census of the State Council (1982): "Standard Classification of Industries and Occupations Used for the Third National Census." Beijing. Neuberger M, Kundi M, Westphal G, Grundorfer W (1986): The Viennnese dusty worker study. In Goldsmith DF, Winn DM, Shy CM (eds): "Silica, Silicosis, and Cancer: Controvery in Occupa tional Medicine." New York: Praeger, pp 415-422. Newhouse ML, Mathews G, Sheikh K, Knight KL, Oakes D, Sullivan KR (1988): Mortality of workers at acetylene production plants. Br J Ind Med 45:63-69. Nomura A (1982): Stomach. In Schottenfeld D, Fraumeni JF Jr.,(eds): "Cancer Epidemiology and Prevention." Philadelphia: Saunders, p. 631. Office of the Shanghai Population Census (1985): "Compilation of the Results of the 1982 Population Census." Shanghai. Ohtsubu K, Saito M (1977): Chronic effects of trichothecene toxins. In Rodricks JV, Hesseltine CW, Mehlman MA (eds): Mycotoxins in Human and Animal Health." Park Forest South, IL: Pathotox, pp 255-262. Park RM, Wegman DH, Silverstein MA, Maizlish NA, Mirer FE (1988): Causes of death among workers in a bearing manufacturing plant. Am J Ind Med 13:569-580. Petersen GR, Milham S, Jr (1980): "Occupational Mortality in the State of California 1 9 5 9 - 6 1 " Cincinnati: DHEW (NIOSH) Pub. No. 80-104, p 40. Purchase IFH, Watt JJV (1970): Carcinogenicity of sterigmatocystin. Food Cosmet Toxicol 8:289. Redmond CK, Strobino BR, Cypress RH (1976): Cancer experience among coke by-product workers. Ann NY Acad Sei 271:102-115. Saftlas AF, Blair A, Cantor KP, Hanrahan L, Anderson HA (1987): Cancer and other causes of death among Wisconsin farmers. Am J Ind Med 11:119-129. Sorahan T, Parkes HG, Veys CA, Waterhouse JA (1986): Cancer mortality in the British rubber industry: 1946-80. Br J Ind Med 43:363-373. Sparks PJ, Wegman DH (1980): Cause of death among jewelry workers. J Occup Med 22:733-736. Spiegelhaider B, Müller J Dräsche H, Preussmann R (1987): N-nitrosodiethanolamine excretion in metal grinders. In Bartsch H, O'Neill I, Schulte-Hermann R (eds): "The Relevance of N-Nitroso Compounds to Human Cancer." Lyon: IARC Sei Pub No. 84, pp 550-552. Swaen GM, Aerdts CW, Slangen JJ (1987): Gastric cancer in coalminers: Final report. Br J Ind Med 44:777-779. Thomas TL, Waxweiler RJ, Moure-Eraso R, Itaya S, Fraumeni JF (1982): Mortality patterns among workers in three Texas oil refineries. J Occup Med 24:135-141. Thomas TL, Waxweiler RJ, Crandall MS, White DW, Moure-Eraso R, Fraumeni JF Jr (1984): Cancer mortality patterns by work category in three Texas oil refineries. Am J Ind Med 6:3-16. Walrath J, Rogot E, Murray J, Blair A (1985): "Mortality Patterns Among U.S. Veterans by Occupation and Smoking Status." NIH Publication No. 85-2756, p 38. Wright WE, Bernstein L Peters JM, Garabrant DH, Mack TM (1988): Adenocarcinoma of the stomach and exposure to occupational dust. Am J Epidemiol 128:64-73. You WC, Blot WJ, Chang YS, Ershow AG, Yang ZT, An Q, Henderson B, Xu GW, Fraumeni JF, Wang TG (1988): Diet and high risk of stomach cancer in Shandong, China. Cancer Res 48:3518-3523.
Occupational Risk Factors for Gastric Cancer in Shanghai, China Robert W. Kneller, MD, MPH, Yu-Tang Gao, MD, Joseph K. McLaughlin, PhD, Ru-Nie Gao, MD, William J. Blot, PhD, Ming-Hao Liu, BS, Ji-Ping Sheng, BS, and Joseph F. Fraumeni, Jr., MD
Occupational data for over 13,000 incident stomach cancer cases reported to the Shang hai Cancer Registry between 1980 and 1984 were compared with 1982 census employ ment information to calculate standardized incidence ratios for stomach cancer in the Shanghai urban area. Several occupations were found to have statistically significantly increased risks for stomach cancer, most notably grain farming and several jobs involv ing potential for exposure to metal, wood, and other dusts and to fossil fuel combustion products. Because of the large numbers involved and consistency of associations, the findings raise hypotheses regarding occupational exposures that warrant further inves tigation. Key words: gastric cancer epidemiology, grain farming, dust, metal working, fossil fuel combus tion products
INTRODUCTION Stomach cancer is the leading cause of cancer mortality in China [Li et al., 1981] and one of the most common cancers worldwide [Page and Asire, 1985], even though its incidence has been declining steadily in the United States [Devesa et al., 1987] and many other industrialized countries. Its causes are poorly understood. Dietary factors are thought to be paramount [Nomura, 1982; Davies, 1981 ; You et al., 1988], but although the role of occupational exposures is not well established, in creased risks for stomach cancer have been found in a number of occupations, including work in the rubber [Sorahan et al., 1986; IARC Monograph, 1982], oil refining [Thomas et al., 1984; Hanis et al., 1979], ball bearing [Park et al., 1988], and jewelry [Dubrow and Gute, 1987; Sparks and Wegman, 1980] industries and in occupations involving high levels of exposure to dust [Wright et al., 1988] and asbestos [Miller, 1978; Clemmesen and Hjalgrim-Jensen, 1981; Newhouse et al., Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD (R.W.K., J.K.M., W.J.B., J.F.F. Jr.). Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China (Y.-T.G., R.-N.G.). Census department, Shanghai Institute of Applied Statistics, Shanghai, China (M.-H.L., J.-P.S.). Address reprint requests to Dr. Kneller, NCI/NIH, Executive Plaza North, Rm 432, Bethesda, MD 20892. In China address reprint requests to Dr. Y.-T. Gao, Dept. of Epidemiology, Shanghai Cancer Institute, 2200 Xie-Tu Rd., Shanghai, 20032, China. Accepted for publication January 4, 1990. © 1990 Wiley-Liss, Inc.
70
Kneller et al.
1988]. The present study analyzes stomach cancer risk by occupation using cancer incidence data for Shanghai, the largest industrial city in China, and employment information from census data. The primary purpose of this analysis is to generate and refine hypotheses regarding occupational risks for stomach cancer. MATERIALS AND METHODS Occupational data from the Shanghai Cancer Registry on incident cancer cases diagnosed between 1980 and 1984 in urban residents aged 30 years and over were compared with population data on occupation from the 1982 census. At the time these data were collected, the Municipality of Shanghai consisted of 11 urban administrative districts and ten rural counties. According to the latest Shang hai census, completed as part of the Third National Census, the population of the urban districts was 6.3 million, while the population of the rural counties was 5.5 million as of July 1, 1982 [Office of the Shanghai Population Census, 1985]. This report focuses on ten of the 11 urban districts, which henceforth are referred to as "urban Shanghai." One small outlying urban district was excluded from the analysis. There were 1.57 million men and 1.55 million women aged 30 years and over who resided in urban Shanghai [Office of the Shanghai Population Census, 1985]. Infor mation on their occupations was included in the census registration form and coded, using standardized nomenclature [National Bureau of Statistics (China), 1982]. Then, tabulations by sex and 5-year age groups were made of numbers of workers in each of eight broad single-digit, 64 general two-digit, and 301 specific three-digit occu pational categories. The census identified 842,735 retired persons. Using a 10% systematic sample of household groups (i.e., units of 10-15 households) 87,485 of these persons were selected for follow-up interviews [Gao et al., in press]. Occupation at time of retire ment was successfully collected on 95.1% of the sample (83,202 persons) and used to estimate the occupational distribution of all retired persons at the time of retirement by age and sex. This enabled us to assign occupational classifications to the entire urban population aged 30 years and over at the time of the census. The Shanghai Cancer Registry has collected cancer incidence and mortality data for the ten urban districts of Shanghai since 1963, except for the years 1966 to 1971 [Muir et al., 1987]. It is one of the contributors to Cancer Incidence in Five Continents published by the International Agency for Research on Cancer [Muir et al., 1987], and the methods and procedures used in the Registry are described therein and elsewhere [Gao, 1984]. After deleting from the Registry those cases whose residence was outside of urban Shanghai, there were 65,474 incident cancer cases among persons aged 30 years and over during the period 1980-1984. Of these cases, 13,489 (21%) were gastric cancers; 9,132 (68%) of these cases were males and 4,357 (32%) were females. Occupation at time of cancer diagnosis or time of retirement was ascertained for 98% of the gastric cancer patients by interviewing either the patients (19.7%) or their next of kin or work supervisors (80.3%). Occupation nomenclature and coding were the same as used in the census [Gao et al., in press]. In order to determine whether occupational data obtained for the cancer cases by our interviews were consistent with employment information obtained by the census, a comparison of occupational classifications by the two methods was made for a random sample of 306 male and 104 female non-retired cancer cases. The one-digit
Occupational Gastric Cancer Risks in Shanghai
71
TABLE I. Standardized Incidence Ratios (SIRs) for Stomach Cancer, by Broad (1-Digit) Occupational Categories, Among Men in Urban Shanghai, 1980-1984 Code
Occupation
No. cases
SIR
6 7,8,9 3 5 4 0,1 2
Agricultural workers Production and transport workers Clerical workers Service workers Commercial (sales) workers Professionals Government officials
124 4,658 478 1,424 750 904 452
159a 109a 104 102 93 71 a 70 a
'p< .01. census occupational classifications for these individuals were the same for 95% of the males and 96% of the females. Concordance at the two-digit level was 90.5% and 91.3% and at the three-digit level 86.6% and 85.6% for males and females, respec tively [Gao et al., in press]. These concordance rates are similar to rates found in linked registry data sets in Scandinavian countries [Malker, 1988]. Age-, sex-, and site-specific cancer incidence rates for urban Shanghai were calculated for 1980-1984. These citywide incidence rates were then applied to the census-derived age- and sex-specific estimates of the number of residents in each occupational category to calculate the expected number of cancer cases in each group. The observed number of cases in each occupation was divided by the expected number of cases and multiplied by 100 to obtain standardized incidence ratios (SIRs). This method of indirect adjustment was used because of the instability of incidence rates in certain occupational categories due to the small numbers of cases in these categories. Statistical significance was tested assuming that the observed numbers of cancer cases followed a Poisson distribution [Bailar and Ederer, 1964]. RESULTS At the broad, one-digit level, male agricultural workers and production and transportation workers had significantly elevated risks for stomach cancer (Table I). In contrast, professionals and government workers had significantly low risks. Fe male agricultural workers also had a significantly increased risk for stomach cancer (SIR = 187, 44 cases, p < .01). Table II lists the two-digit occupational categories with significantly high risks of stomach cancer in men and the three-digit occupational categories therein. At the two-digit level, farmers had a greater than twofold risk, while administrative clerks, public service workers, leather/fur processors, wood workers, transport workers, freight handlers/moving equipment operators, and metal workers (except those in refining and primary metal processing) had significantly elevated risks, though these were within 40% of expected values. At the three-digit level, grain farmers had the most striking excess risk (fourfold), with 89 cases. Risk for railway engine drivers/ firemen also was close to four times higher than expected. A potential for heavy dust exposure, especially wood or metal dust, characterized several of the high-risk oc cupational groups, including wood sawyers and plywood workers, cabinetmakers, precision instrument makers, blacksmiths, and metal grinders.
TABLE II. Statistically Significant Standardized Incidence Ratios (SIRs) for Stomach Cancer, by General (2-Digit) Occupational Categories, With Specific (3-Digit) Occupations, Among Men in Urban Shanghai, 1980-1984 Code
Occupation
3.1 Administrative clerks 3.11 Government and business clerks 3.12 Secretaries 3.19 Other clerical workers Other 3-digit categories combined for convenience 5.1/5.2 Public service workers 5.11 Waiters 5.12 Hotel and restaurant personnel 5.15 Transportation attendants for buses, trains, and boats 5.16 Ticket takers for trains, theaters, and public baths 5.21 Fuel suppliers 5.22 Sanitation personnel, street cleaners, and garbage men 5.23 Misc. workers (doormen, messengers, janitors, etc.) 5.29 Other public service workers Other 3-digit categories combined for convenience 6.1 Farmers 6.11 Grain farmers 6.13 Vegetable farmers 6.14 Tea, vineyard, and orchard farmers 6.19 Other farmers 7.6 Leather and fur processors 7.61 Tanners, feltmongers, and pelt dressers 7.62 Leather products workers 8.0 Wood preparation workers, cabinetmakers and bamboo, hemp, rattan, and straw product makers 8.02 Wood sawyers, plywood makers, and related wood-processing workers 8.03 Cabinetmakers 8.04 Construction carpenters 8.09 Other wood and bamboo workers Other 3-digit categories combined for convenience 8.4 Blacksmiths, toolmakers, and machine-tool operators 8.41 Blacksmiths, hammersmiths, and forging-press operators 8.42 Toolmakers, metal patternmakers, and metal workers 8.43 Machine-tool setters 8.44 Metal grinders, polishers, tool sharpeners, and machine-tool operators 8.49 Other blacksmiths, toolmakers, and machine-tool operators 8.5 Machinery fitters, machine assemblers, and precision instrument makers (except electrical) 8.51 Machinery fitters and machine assemblers 8.52 Machinery, motor vehicle, and aircraft engine mechanics 8.53 Watch, clock, and precision instrument makers 8.59 Other machinery fitters, assemblers, and precision instrument makers 8.8 Plumbers, welders, and sheet metal and structural metal preparers and erectors 8.81 Plumbers and pipe fitters 8.82 Welders and flame cutters 8.83 Sheet-metal workers 8.84 Structural metal preparers and erectors
Cases
SIR
370 59 17 283 11
IIIa
1,153
107 32 25 51 23 66 757 22 14 104 89 12 1 2 60 5 55
36 104 211"
67 110b 134a
117 162a 150a
133 157b 109a
70 81 232" 402"
92 203 22a 133a
94 150a
280 25 36 84 127 8 474
176a 147a
42 193 3
156b
111 305
191
141b
45
79
293 31
119a
232 23
126b 172a
7
47a
190 17 38 133 2
127b
70b 195b
63 120"
91
111 119 140b
27a (continued)
Occupational Gastric Cancer Risks in Shanghai
73
TABLE II. Statistically Significant Standardized Incidence Ratios (SIRs) for Stomach Cancer, by General (2-Digit) Occupational Categories, With Specific (3-Digit) Occupations, Among Men in Urban Shanghai, 1980-1984 (continued) Code
Occupation
9.4 Material handling and related equipment operators, dockers, and freight handlers 9.41 Dockers and freight handlers 9.42 Crane and hoist operators 9.43 Earth-moving and related machinery operators 9.49 Other material handling equipment operators 9.5 Transportation equipment operators 9.51 Ships' deck ratings, barge crews, boatmen, and ships' engine-room ratings 9.52 Railway engine drivers and firemen 9.54 Automobile and truck drivers 9.57 Rickshaw and handcart drivers Other 3-digit categories combined for convenience a
Cases
SIR
612 558 51 2 1 485
139" 154b
130 14 153 151 37
81 22a 17a 123b
114 363"
115 153b
83
p < .05. p < .01.
b
Table III lists 11 other three-digit occupations with significantly elevated risks for men that are not included within the two-digit categories listed in Table II. SIRs for nurses, pesticide production workers, and petroleum refinery workers were more than four times greater than expected, although the numbers of cases were small. Laboratory technicians had a twofold excess risk. Excesses of nearly 50% were observed for metal smelting and metal rolling mill workers, boiler firemen, and textile machinery mechanics. Elevated risks for women paralleled those for men in several occupations: grain farmers (SIR = 414, 36 cases, p < .01); wood sawyers, plywood makers and related workers (SIR = 308, 9 cases, p < .01); machinery, motor vehicle, and aircraft engine mechanics (SIR = 231, 15 cases, p < .01); sanitation personnel, street cleaners, and garbage collectors (SIR = 193, 32 cases, p < .01); and rickshaw and handcart drivers (SIR = 172, 24 cases, p < .05). The only occupations with more than 5 female cases that had significantly elevated risks for women but not for men were plastic manufacturing and plastic products makers (41 cases, SIR = 160, p < .01), knitters (83 cases, SIR = 148, p < .01), and weavers (178 cases, SIR = 117, p < .05). DISCUSSION
The role of occupational exposures in stomach cancer remains unclear despite a variety of clues. With more than 13,000 cases of stomach cancer, the Shanghai occupation-cancer registry enabled us to look for occupational associations in a coun try where this issue has not been systematically evaluated. Our survey revealed several etiologic leads, some of which have been previously reported in other coun tries. Since there was close correspondence between occupational risks for men and women, we shall discuss only risk factors for men unless specifically noted.
74
Kneller et al. TABLE III. Statistically Significant Standardized Incidence Ratios (SIRs) for Stomach Cancer, by Specific (3-Digit) Occupations Not Included in Table II, Among Men in Urban Shanghai, 1980-1984 Code
Occupation
0.75 0.76 7.21
Nurses Laboratory technicians Metal smelting, converting, and refining furnacemen Metal rolling-mill workers Pesticide production workers Petroleum refinery workers Rubber manufacturing and rubber product makers (except tires) Textile machinery mechanics Bleachers, dryers, and textile product finishers Electricians (wiremen), electrical linemen, and cable joiners Boiler firemen
7.22 7.33 7.36 7.41 7.53 7.56 8.64 9.33 a
Cases
SIR
5 13
574 b 201 a
83 34 3 5
149b 147a 564 a 439 a
42 168 91
139a 147b 126a
123 118
124a 159"
p < .05. p < .01.
b
Prior studies have reported elevated stomach cancer risks among farmers as a group, with some investigators suggesting that high nitrate levels in drinking water may be involved [Blair et al., 1985]. In our study, the high SIR among farmers was entirely accounted for by a fourfold elevated risk of stomach cancer among grain farmers. This finding is consistent with a death certificate analysis of Iowa farmers, which found a geographic correlation between stomach cancer rates and yields of corn per acre by county [Burmeister et al., 1989], although a similar association was not found in Wisconsin [Saftlas et al., 1987]. While it is possible that the numbers of cases among Shanghai grain farmers may be inflated due to migration into the urban districts to seek medical care, any over-estimation is likely to be small because we excluded persons whose official residence was outside the ten urban survey districts, and it is very difficult for a rural dweller to change official residence to an urban district [Gao et al., in press]. Farmers account for 0.8% of the working population of urban Shanghai, most living in the peripheral urban districts [Gao et al, in press]. Due to contact with moldy grain, grain farmers may have greater exposure to fungal toxins such as aflatoxins, tricothecenes, or sterigmatocystin, which have been reported to cause gastric neoplasms in laboratory animals [Butler and Barnes, 1966; Ohtsubu and Saito, 1977; Purchase and Watt, 1970]. Grain farmers may also have greater exposure to fungicides. A case-control study of non-Hodgkin's lymphoma in Kansas, a major wheat-producing state, found that cases were more likely than controls to have treated seeds with fungicides [Hoar et al., 1986]. To our knowledge, however, there have been no reports linking stomach cancer in grain or other farmers to use of fungicides, insecticides, or herbicides. It is noteworthy that Shanghai pesticide production work ers had an SIR more than five times greater than expected (Table III); however, Shanghai grain millers and oil pressmen showed no excess risk. Several other occupational associations identified in Shanghai are consistent with surveys from other countries. The increased stomach cancer risks we observed among metal grinders/polishers and machinery mechanics are consistent with pub-
Occupational Gastric Cancer Risks in Shanghai
75
lished reports [Park et al., 1988; Jarvholm et al., 1982; Dubrow and Wegman, 1984; Walrath et al., 1985; Bross et al., 1978] and may possibly result from exposure to lubricating oils, to N-nitroso or anti-rust compounds contained in lubricating oils, or to polishing compounds [Park et al., 1988; Jarvholm et al., 1982]. One study among grinders revealed rising urinary nitrosamine levels as the work week progressed [Spiegelhaider et al., 1987]. In addition, our findings of elevated risk among rubber and oil refinery workers have been noted elsewhere [Sorahan et al., 1986; IARC Monograph, 1982; Thomas et al., 1982, 1984; Hanis et al., 1979], as have the high risks we observed among several woodworking occupations (cabinetmakers, wood sawyers/plywood makers, and other wood workers) [Dubrow and Wegman, 1984; Walrath et al., 1985; Milham, 1983; Petersen and Milham, 1980]. In Shanghai, the increased risk among leather product workers (excluding tanners and shoemakers) is similar to findings in a Massachusetts survey [Dubrow and Wegman, 1984], while the elevated risk among railway engine drivers/firemen resembles the observations for locomotive engineers among U.S. veterans [Walrath et al., 1985]. Finally, the in creased risk among female plastic workers is interesting in view of similar findings in Massachusetts [Dubrow and Wegman, 1984]. These results point to exposure categories that may warrant further examination. First, elevated risks were found for a number of dust-exposed occupations, including those with high levels of metal, wood, and textile dust exposure. The elevated risks of stomach cancer among foundry workers [Fletcher, 1986], cement workers [McDowall, 1984], coal miners [Bridbord et al., 1979], textile machinery operators [Bross et al., 1978], and workers in other dusty occupations [Bross et al., 1978; Neuberger et al., 1986] have suggested that heavy dust exposure may be a risk factor for gastric cancer. Long-term exposure to asbestos fiber dust has been associated with an increased risk of gastric and other digestive tract tumors [Miller, 1978]. However, there has been little evidence of a dose-response relationship for dust-related occu pations, and some studies have shown no evidence of increased risk [Swaen et al., 1987; Amandus, 1986]. Also, it has been hard to disentangle confounding variables such as smoking and socioeconomic status [Creagan et al., 1974]. One study sug gested that the increased risk associated with coal dust exposure is limited to miners who smoke cigarettes [Ames, 1983]. A recent Los Angeles study found an associa tion between stomach cancer incidence and occupational dust exposure (proportional incidence ratio [PIR] = 1.3, 95% CI = 1.2—1.4), even after adjusting for ethnic background and immigrant and socioeconomic status, although cigarette smoking was not controlled for [Wright et al., 1988]. In those parts of the stomach most likely to develop cancer, the antrum and pylorus, slightly higher risks were observed for heavy versus moderate dust exposure. Based on these findings, it was suggested that reductions in occupational dust exposure may have contributed to the declining stom ach cancer incidence in the United States [Wright et al., 1988]. Second, we found that stomach cancer risks were elevated among workers in high-temperature environments near open fossil-fuel combustion sources (e.g., rail way engine drivers, boiler firemen, blacksmiths, metal rolling-mill workers, and metal smelting/refining furnacemen). This observation is consistent with the excess stomach cancer risks reported among nickel [Haas and Schottenfeld, 1978] and steel [Fletcher, 1988] refinery workers and roofers [Hammond et al., 1976], although the findings for coke oven workers [Redmond et al., 1976] and coal gas workers [Doll et al., 1972] have been unremarkable. In Shanghai, further studies are needed to de-
76
Kneller et al.
termine exposure levels among these workers to polyaromatic hydrocarbons, Nnitroso compounds, asbestos, and other agents. Because the risk of stomach cancer is correlated with low socioeconomic status in various countries [Logan, 1982], it is possible that social class differentials con tributed to the low risks observed for professional and government jobs and the elevated risks for several blue-collar occupations. In a rural area of China, stomach cancer cases were 30% more likely than randomly selected controls to be from low-income rather than high-income households [You et al., 1988]. Similar socioeconomic gradients were seen in Japan, where stomach cancer incidence rates are equivalent to those in China [Muir et al., 1987; Hirayama, 1971], although stronger socioeconomic effects have been reported in Great Britain [Logan, 1982]. Several factors, however, suggest that socioeconomic gradients are not the sole explanation for the high-risk occupations identified in this survey. The SIRs observed for Shanghai grain farmers, metal workers, wood workers, leather products workers, petroleum refinery workers, dust-exposed workers, workers exposed to high-temperature combustion products, and female plastics workers and knitters appear too high to be accounted for even by fairly strong social class confounding [Logan, 1982; Hirayama, 1971]. Furthermore, the relatively equal distribution of income and social benefits, such as free medical care and highly subsidized housing in Shanghai since the 1950s, should have tended to reduce dif ferentials in risk factors related to socioeconomic status among workers. Moreover, during the period of the study, the ratios of highest to lowest quantiles of income within occupational groups and the ratios of average incomes between occupational groups did not exceed two in Shanghai (Shanghai Bureau of Statistics: Personal Communi cation). Lifestyle differences that may be linked to both socioeconomic factors and gastric cancer, however, cannot be ruled out. Several other caveats should be remembered when interpreting these data. The classification of occupations provides no direct information on actual exposure. In addition, no data are available on other risk factors for gastric cancer whose frequency may differ among occupational groups, most notably dietary habits and perhaps cigarette smoking [Nomura, 1982; You et al., 1988]. The problem of multiple com parisons must be acknowledged, since a large number of employment categories were examined, and some may have achieved statistical significance by chance alone. We have not performed statistical adjustments for this, since the study is hypothesisgenerating in nature. We intend, however, to launch analytical studies focusing on occupational exposures suggested in this survey. Finally, no data are available on duration of occupation, although job changes are typically less frequent in Shanghai than in urban areas of Western countries. Based upon responses to interviews ad ministered to all the cancer cases and to 10% of all the retirees in Shanghai, less than 8% of persons in the one-digit categories that contained most of the high-risk occu pations changed jobs within 5 years of retirement [Gao et al., in press]. Despite the generic limitations of this survey, the findings from this large data base should help to generate and refine etiologic leads and to set priorities for ana lytical studies aimed at evaluating occupational and environmental determinants of stomach cancer.
REFERENCES Amandus HE (1986): Mortality from stomach cancer in United States cement plant and quarry workers, 1950-80. Br J Ind Med 43:526-528.
Occupational Gastric Cancer Risks in Shanghai
77
Ames RG (1983): Gastric cancer and coal mine dust exposure. A case-control study. Cancer 52:13461350. Bailar JL, Ederer F (1964): Significance factors for the ratio of a Poisson variable to its expectation. Biometrics 20:639-643. Blair A, Malker H, Cantor KP, Burmeister L, Wiklund K (1985): Cancer among fanners: A review. Scand J Work Environ Health 11:397-407. Bridbord K, Costello J, Gamble, Groce D, Hutchison M, Jones W, Merchant J, Ortmeyer C, Reger R, Wagner WL (1979): Occupational safety and health implications of increased coal utilization. Environ Health Perspect 33:285-302. Bross ID, Viadana E, Houten L (1978): Occupational cancer in men exposed to dust and other environ mental hazards. Arch Environ Health 32:3000-3007. Burmeister LF, Everett GD, Van Lier SF, Isacson P (1989): Selected cancer morality and farm practices in Iowa. Am J Epidemiol 118:72-77. Butler WH, Barnes JM (1966): Carcinoma of the glandular stomach in rats given diets containing aflatoxin. Nature 209:90. Clemmesen J, Hjalgrim-Jensen S (1981): Cancer incidence among 5686 asbestos-cement workers fol lowed from 1943 through 1976. Ecotoxicol Environ Safety 5:15-23. Creagan ET, Hoover RN, Fraumeni JF (1974): Mortality from stomach cancer in coal mining regions. Arch Environ Health 28:28-30. Davies JM (1981): Mortality trends for stomach cancer in England and Wales. Br J Cancer 44:879-885. Devesa SS, Silverman DT, Young JL, Pollack ES, Brown CC, Horn JW, Percy CL, Myers MH, McKay FW, Fraumeni JF (1987): Cancer incidence and mortality trends among whites in the United States, 1947-84. JNCI 79:701-707. Doll R, Vessey MP, Beasley RWR (1972): Mortality of gas workers. Final report of a prospective study. Br J Ind Med 29:394-406. Dubrow R, Wegman DH (1984): "Occupational Characteristics of Cancer Victims in Massachusetts: 1971-1973." Cincinnati: DHHS (NIOSH) Publication No. 84-109, pp 65,89,91,94,96. Dubrow R, Gute DM (1987): Cause-specific mortality among Rhode Island jewelry workers. Am J Ind Med 12:579-593. Fletcher AC (1986): The mortality of foundry workers in the United Kingdom, In Goldsmith DF, Winn DM, Shy CM (eds): "Silica, Silicosis, and Cancer: Controvery in Occupational Medicine." New York: Praeger, pp 385-401. Fletcher AC (1988): The mortality of steel foundry workers: A cohort study. Diss Abstr Int [B] 49:85 (full text available from University Microfilms International, An Arbor, MI, as order no. AADDX80355). Gao Yu-Tang (1984): Cancer incidence in Shanghai during 1973-77. Nati Cancer Inst Monogr 62:43-46. Gao YT, McLaughlin JK, Gao RN, Kneller RW, Liu MH, SHeng JP, Blot WJ (1990): Investigation of occupational cancer incidence in Shanghai: Background and methods. Shanghai Tumor (in press). Haas JF, Schottenfeld D (1978): Epidemiology of gastric cancer. In Lipkin M, Good RA (eds): "Gas trointestinal Tract Cancer." New York: Plenum, pp 173-206. Hammond EC, Selikoff IJ, LawtherPL, Seidman H (1976): Inhalation of benzopyrene and cancer in man. Ann NY Acad Sei 271:116-124. Hanis NM, Stavraky KM, Fowler JL (1979): Cancer mortality in oil refinery workers. J Occup Med 21:167-174. Page HS, Asiré AJ (1985): "Cancer Rates and Risks," 3d ed. (NIH Publication No. 85-691), U.S. Department of Health and Human Services. Hirayama T (1971): Epidemiology of stomach cancer. Gann Monogr Cancer Res 11:3-19. Hoar SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Fraumeni JF, Jr (1986): Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 256:1141-1147. International Agency for Research on Cancer (1982): "Monograph on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Vol. 28. The Rubber Industry." Lyon: IARC. Jarvholm B, Thiringer G, Axelson O (1982): Cancer morbidity among polishers. Br J Ind Med 39: 196,197. Li JY, Liu BQ, Chen ZJ, Sun XD, Rong SD (1981): Atlas of cancer mortality in the People's Republic of China. Int. J. Epidemiol. 10:127-133. Logan WP (1982): "Cancer Mortality by Occupation and Social Class 1851-1971." London: Her Majesty's Stationery Office.
78
Kneller et al.
Malker HSR (1988): Register-epidemiology in the identification of cancer risks. Arbete Och Halsa 21:7-50. McDowall ME (1984): A mortality study of cement workers. Br J Ind Med 41:179-182. Milham S, Jr (1983): "Occupational Mortality in Washington State: 1950-1979." Cincinnati: DHHS (NIOSH) Pub. No. 83-116, p 1593. Miller AB (1978): Asbestos fibre dust in gastro-intestinal malignancies: Review of the literature with regard to a cause effect relationship. J Chronic Dis 31:23-33. MuirC, Waterhouse J, MackT, Powell J, Whelan S (eds) (1987): "Cancer Incidence in Five Continents: Vol V . " Lyon: IARC Scientific Pub. No. 88, pp 394-97. National Bureau of Statistics, General Administration of National Standards, Office of the National Census of the State Council (1982): "Standard Classification of Industries and Occupations Used for the Third National Census." Beijing. Neuberger M, Kundi M, Westphal G, Grundorfer W (1986): The Viennnese dusty worker study. In Goldsmith DF, Winn DM, Shy CM (eds): "Silica, Silicosis, and Cancer: Controvery in Occupa tional Medicine." New York: Praeger, pp 415-422. Newhouse ML, Mathews G, Sheikh K, Knight KL, Oakes D, Sullivan KR (1988): Mortality of workers at acetylene production plants. Br J Ind Med 45:63-69. Nomura A (1982): Stomach. In Schottenfeld D, Fraumeni JF Jr.,(eds): "Cancer Epidemiology and Prevention." Philadelphia: Saunders, p. 631. Office of the Shanghai Population Census (1985): "Compilation of the Results of the 1982 Population Census." Shanghai. Ohtsubu K, Saito M (1977): Chronic effects of trichothecene toxins. In Rodricks JV, Hesseltine CW, Mehlman MA (eds): Mycotoxins in Human and Animal Health." Park Forest South, IL: Pathotox, pp 255-262. Park RM, Wegman DH, Silverstein MA, Maizlish NA, Mirer FE (1988): Causes of death among workers in a bearing manufacturing plant. Am J Ind Med 13:569-580. Petersen GR, Milham S, Jr (1980): "Occupational Mortality in the State of California 1 9 5 9 - 6 1 " Cincinnati: DHEW (NIOSH) Pub. No. 80-104, p 40. Purchase IFH, Watt JJV (1970): Carcinogenicity of sterigmatocystin. Food Cosmet Toxicol 8:289. Redmond CK, Strobino BR, Cypress RH (1976): Cancer experience among coke by-product workers. Ann NY Acad Sei 271:102-115. Saftlas AF, Blair A, Cantor KP, Hanrahan L, Anderson HA (1987): Cancer and other causes of death among Wisconsin farmers. Am J Ind Med 11:119-129. Sorahan T, Parkes HG, Veys CA, Waterhouse JA (1986): Cancer mortality in the British rubber industry: 1946-80. Br J Ind Med 43:363-373. Sparks PJ, Wegman DH (1980): Cause of death among jewelry workers. J Occup Med 22:733-736. Spiegelhaider B, Müller J Dräsche H, Preussmann R (1987): N-nitrosodiethanolamine excretion in metal grinders. In Bartsch H, O'Neill I, Schulte-Hermann R (eds): "The Relevance of N-Nitroso Compounds to Human Cancer." Lyon: IARC Sei Pub No. 84, pp 550-552. Swaen GM, Aerdts CW, Slangen JJ (1987): Gastric cancer in coalminers: Final report. Br J Ind Med 44:777-779. Thomas TL, Waxweiler RJ, Moure-Eraso R, Itaya S, Fraumeni JF (1982): Mortality patterns among workers in three Texas oil refineries. J Occup Med 24:135-141. Thomas TL, Waxweiler RJ, Crandall MS, White DW, Moure-Eraso R, Fraumeni JF Jr (1984): Cancer mortality patterns by work category in three Texas oil refineries. Am J Ind Med 6:3-16. Walrath J, Rogot E, Murray J, Blair A (1985): "Mortality Patterns Among U.S. Veterans by Occupation and Smoking Status." NIH Publication No. 85-2756, p 38. Wright WE, Bernstein L Peters JM, Garabrant DH, Mack TM (1988): Adenocarcinoma of the stomach and exposure to occupational dust. Am J Epidemiol 128:64-73. You WC, Blot WJ, Chang YS, Ershow AG, Yang ZT, An Q, Henderson B, Xu GW, Fraumeni JF, Wang TG (1988): Diet and high risk of stomach cancer in Shandong, China. Cancer Res 48:3518-3523.
