Occupations and Breast Cancer
Evaluation of associations between breast cancer and workplace exposures

A review prepared for the
Ontario Occupational Disease Panel (Industrial Disease Standards Panel)
Ministry of Labour of Ontario
by France Labrèche, PhD, Epidemiologist

Occupational and Environmental Health Unit
Montreal Public Health Department and
Joint Departments of Epidemiology and Biostatistics, and Occupational Health
McGill University, Montréal

December 23, 1997


Background and scope of evaluation

This document was prepared as a tool to assist the Ontario Occupational Disease Panel in its examination of the possible occupational associations of breast cancer. The present epidemiologic review evaluates:

  • workplace associations for female and male breast cancer;
  • the evidence concerning environmental (pesticides) exposures, especially as they might pertain to farm workers;
  • and, to a lesser extent, any other possibly significant associations.
  • The section on female breast cancer is fairly exhaustive, but because of restricted time, the section on male breast cancer is less thorough.

    Introduction

    Breast cancer will affect one in nine Canadian women during their lifetime and it is the leading cancer among women; one in 25 women will die from it in Canada, making breast cancer the second cause of cancer deaths, overtaken by lung cancer in 1993. The 1997 incidence rates in Canada range from 93 to 112 per 100,000 [National Cancer Institute of Canada, 1997]. The average incidence rate over 1983-1987 was reported to be 91.1 per 100,000 (ranging from 35.5 to 103.9 per 100,000) [Parkin et al., 1992]. It is estimated that over 18,000 women will be diagnosed with breast cancer in 1997 and more than 5,000 will die of it.

    Incidence rates of female breast cancer have increased over the past few decades in most western countries [Stevens et al., 1982; Holford et al., 1991; Coleman et al., 1993] especially among post-menopausal women [National Cancer Institute of Canada, 1993]. The reasons for this increase are largely unknown, but could be related to early detection in mass screening programs, to temporal changes in recognized and suspected risk factors, to changes in the pathologic definition of breast cancer or to an artifact of detecting "histologically malignant but biologically benign" tumours [Doll and Peto, 1981], or to other unidentified risk factors. It is likely that the known risk factors cannot account for a large fraction of cases or for all of the growth in incidence rates [Kelsey, 1993]; estimated figures to that effect rang from 21% [Seidman et al., 1982] to 41% [Madigan et al., 1995]. Mortality rates have remained fairly stable, declining slightly over recent years [National Cancer Institute of Canada, 1993].

    By contrast, male breast cancer incidence rates are very low, approximately 100 times lower than in women, and have remained stable, as have the mortality rates, for the last 40 years [Sasco et al., 1993; Thomas, 1993]. The highest incidence rate in Canada over 1983-1987 is reported to be in Nova Scotia and New Brunswick, at 0.9 case per 100,000 [Parkin et al., 1992]; the Canadian average was 0.7 per 100,000 for the same period.

    Methods

    Epidemiological studies with the potential for investigating associations of breast cancer and occupation were identified through MEDLINE searches, published reviews of literature, review of each paper on cancer published in twenty major journals between 1970 and September 1997, and from examining reference lists of retrieved pertinent papers. Only papers published in peer-reviewed journals were retained, excluding abstracts (they often do not contain sufficient information), and articles published in English or in French were retrieved. Studies on female breast cancer published until 1994 had already been reviewed thoroughly for a previous publication [Goldberg and Labrèche, 1996]: the female breast cancer part of the present work is an update of that review. Two recent reviews on male breast cancer were used as a starting point for the male breast cancer part [Sasco et al., 1993; Thomas, 1993]; these papers mentioned only EMF exposure as a possible occupational factor in male breast cancer.

    Because of time constraints, the MEDLINE search on male breast cancer was restricted to publications that contained the MeSH term: breast neoplasms/male'; this means that general mortality studies where figures are reported for male breast cancer, but where it was not mentioned in the abstract, could have not been all indexed in MEDLINE and would thus have been missed.

    More than 170 reports from over 130 independent studies that presented risk estimates for breast cancer were reviewed. Studies were classified by type of design, namely descriptive studies including analysis of routinely collected data, general population surveys and registry linkage studies, and analytical studies including case-control and cohort studies. Some investigations did not however fit neatly into one category. Case reports and case series were not considered in this review because of their anecdotal nature and descriptive studies on cancer in males were not reviewed.

    Investigations based on routinely collected data, labelled as descriptive studies here, may convey spurious conclusions if used by themselves, although they can be used for generating hypotheses. The principal limitations of descriptive studies include: 1) misclassification of disease status, 2) misclassification of exposure, 3) lack of control of confounders and 4) absence of exposure-response indices. 1) Misclassification of disease status can lead to reductions in statistical power and attenuation of risk ratios. Mortality data are more susceptible to these types of problems than incidence data. 2) Misclassification of exposure through the use of coarse occupational categories will lead to an attenuation of risk ratios. In the studies we reviewed, exposure was usually classified in terms of the last occupation (or industry) or the occupation of the longest duration. This can also lead to bias, possibly away from the null, if workers changed occupations because of illness. Notable exceptions were the Chinese study by Zheng and coworkers [1993], in which occupational histories were obtained directly from subjects (although denominators were based on census data). 3) Inability to account for key confounding factors may lead to incorrect inferences. In none of the investigations based on administrative data were important risk factors for breast cancer accounted for. That incorrect conclusions may be drawn from descriptive studies is showed by the observation that although increased risks of developing breast cancer for clerical and white collar jobs were observed in studies using administrative data, no association was observed in the cohort or case-control studies. It is also possible that the studies of exposure to extremely low frequency electromagnetic fields, also based on routinely collected data, were also biased [Trichopoulos, 1994]. 4) Lastly, no estimates of risk by duration of employment, latency, or other indices of exposure-response were presented in the reviewed papers, thus making it difficult to assess the veracity of the associations.

    More weight is given in this paper to analytical studies because of their better adjustment for confounding factors and more careful ascertainment of disease and exposure or occupation. Standardised ratios were preferred to proportionate ratios, because the former are more robust against the healthy worker effect'. Incidence data were preferred to mortality data because of the relatively long survival from breast cancer (5-year survival of 75% in Canada). When more than one comparison group was used, the risk estimate obtained with the most appropriate one was retained (i.e. local versus national, working population versus population including the unemployed, comparable or similar occupations versus dissimilar occupations). Increased comparability also makes studies done in North America preferable to studies from other parts of the world because more similar types of industries and occupational exposures, lifestyles and genetic make-up of the population are expected within a continent.

    In terms of other potential confounding factors, as reproductive factors are distributed unevenly in the population, the exclusion of homemakers in the comparison group could help decrease part of the confounding effect of reproductive factors. This has been verified in a descriptive study on teachers and nurses [King et al., 1994], where the PMR estimates were reduced when homemakers were removed from the reference group, thus suggesting that some or all of the excess risk may be due to confounding by reproductive factors.

    Results

    Most of the published studies relevant to breast cancer and occupational exposures used routinely collected data and covered a wide variety of occupational circumstances, from different parts of the world. These descriptive studies can be considered as indicators of possible associations, but because of their methodological weaknesses, stated before, one must rely on analytical studies to draw conclusions on the possibility or probability that an association seen may be judged as causal.

    Among the analytical studies, occupational cohort studies, especially of mortality, are by far the most numerous. More than thirty different occupations or industries were investigated in the cohort studies, as well as close to 20 different exposures to chemical agents. Although we calculated for the females breast cancer studies that statistical power (to be able to show a risk of 2) was above 80 percent in about three quarters of the studies, the small number of observed cases indicates that the power to detect excess risks in sub-groups and to test for trends in exposure was generally low [Goldberg and Labrèche, 1996]. A variety of indices or surrogates of exposure were used in these studies, but in fewer than 15 studies were breast cancer risks actually presented according to level or duration of exposure.

    Although numerous case-control studies have been conducted on female breast cancer, only seven of them documented occupation as a potential risk factor, in addition to some that reported solely on physical activity in relation to occupation [Vena et al., 1987; Vihko et al., 1992; Dosemeci et al., 1993; Zheng et al., 1993; D'Avanzo et al., 1996; Coogan et al., 1997]. Of the seven case-control studies identified, four were population-based [Williams et al., 1977; Franceschi et al., 1993; Habel et al., 1995; Coogan et al., 1996a; Coogan et al., 1996b], one was based on patients admitted to Roswell Park Memorial Institute, Buffalo, NY [Decoufle et al., 1977], one was a nested study among patients referred to a breast cancer screening clinic in New York City [Koenig et al., 1991], and the seventh was a study within a cohort of radiologic technologists [Morin Doody et al., 1995]. In general, the response rates were adequate and control populations were selected appropriately. Franceschi et al. [1993] focused on farming and agricultural occupations and Koenig et al. [1991] studied cosmetologists. As male breast cancer rates are very low, its rarity explains the relative paucity of published large case-control studies; however, in most of these studies, occupation has been documented.

    As requested by the Ontario Disease Panel, the studies published on exposure to electromagnetic fields and organochlorine compounds, with a special reference to pesticides and farming, will be reviewed in more detail here.

    Potential exposure to electromagnetic fields: Stevens and colleagues hypothesized that breast cancer risk may be increased by exposure to electromagnetic fields (EMFs): through a reduction in melatonin production, these fields could interfere with the oncostatic properties of melatonin and allow levels of estrogen and prolactin to increase [Stevens, 1987; Stevens et al., 1992]. Thus, EMFs may indirectly affect hormonal secretions thereby increasing breast cancer risk. Although several authors have debated the issue, few epidemiologic studies have been carried out among workers exposed to EMFs. A few descriptive studies have shown associations between female breast cancer and a variety of occupations, such as electronic engineering technicians, telephone operators, communication workers, and electrical workers (Table 1) [Doebbert et al., 1988; Bulbulyan et al., 1992; Aronson and Howe, 1994; Loomis et al., 1994; Cantor et al., 1995; Morton, 1995], and one study showed increased risks among office workers, engineers and technicians employed in the telephone industry, with higher risks among black women [Dosemeci and Blair, 1994]. One descriptive study showed increased risks of male breast cancer among workers in electrical transportation [Tynes and Andersen, 1990].

    Two cohort studies among females and five among males were identified (Table 1). One cohort study of telecommunications workers, that had a 75% power to detect a two-fold risk, did not show an increased risk of female breast cancer [Vågerö et al., 1985]. A more recent cohort study of Norwegian female radio and telegraph operators (mostly working on merchant ships) showed an increased incidence of breast cancer of 1.5 compared to the general population of Norway, based on 50 cases (95% CI=1.1-2.0); cases over 50 years old at time of diagnosis had a significant increase in risk with duration of employment and exposure to shift work including night shift [Tynes et al., 1996]. One cohort study, based on only 2 cases, suggested an association among male telephone workers (SIR=6.5, 95% CI=0.79-23.5) [Matanoski et al., 1991]. A Norwegian study has shown an association with employment in "electrical occupations" (12 cases; SIR=2.07, 95% CI=1.07-3.61) [Tynes et al., 1992]. Two large cohort studies of male electric utility workers were not conclusive as breast cancer was concerned: one presented as a case-control analysis from Ontario, Québec and France [Thériault et al., 1994], and one in the United States [Savitz and Loomis, 1995]. An increased incidence of breast cancer was reported among a Swedish cohort of male railway workers, based on 3 cases among engine drivers and conductors (RR=4.9, 95% CI=1.6-15.7); these workers were reported to be exposed to respective average daily means of 4.03:T and 0.61:T, and daily medians of 0.58:T and 0.36:T, for drivers and conductors [Floderus et al., 1994].

    Two case-control studies among females and four among males were found regarding exposure to EMFs (Table 1). One case-control study did not report increased risks among female telephone and other communication operators, with an OR of 0.8 (22 cases; 95% CI=0.4-1.4 ) [Habel et al., 1995]. A recent population-based case-control study found a modest increase in risk for women whose usual job had entailed exposures to 60-Hz magnetic fields (55 cases; adjusted OR=1.43, 95% CI= 0.99-2.09); the increase was however statistically significant for pre-menopausal women (20 cases; adjusted OR=1.98, 95% CI=1.04-3.78). When subgroups of occupations were considered, computer equipment operators had an adjusted OR=1.79 (31 cases; 95% CI=1.03-3.11) [Coogan et al., 1996b]. A large study of male breast cancer (227 cases) found a six-fold increase in electric trades and related occupations (13 cases; OR=6.0, 95% CI=1.7-21) [Demers et al., 1991]. Another case-control study, based on registry data, found an elevated risk among male electrical workers', less than 65 years old at diagnosis, (3 cases; OR=2.2, 95% CI=0.6-7.8) and among telephone workers (1 case; OR=9, 95% CI=0.9-88.7) [Loomis, 1992]. A small case-control study of male breast cancer did not find an excess of EMF-exposed jobs among cases [Rosenbaum et al., 1994]. The most recent case-control study, from Sweden, did not find any increased risk for men exposed at levels of 0.29 to more than 0.41 :T; a job-exposure matrix developed for another study involving EMFs was applied to the reported job titles. The corresponding odds ratios were 0.9 (11 cases; 95% CI=0.4-2.2) and 0.9 (4 cases; 95% CI=0.3-2.7) [Stenlund and Floderus, 1997].

    Unfortunately, in most of the published studies, the exposure data are either more qualitative than quantitative, or based solely on a job title, and information on risk factors other than age is usually missing or indirect at best. Moreover, except for two case-control studies, information on the disease comes from death certificates or disease registries (without histologic confirmation). Several sources of inaccuracy are attached to death certificates, including diagnostic problems (the treating physician may not be aware of the true cause of death or may have difficulty deciding on the direct cause of death), recording problems (especially if the physician who fills the form is not used to the form) and coding problems (arising from disagreement between the coder and the physician on the selection of cause of death or simply clerical coding errors). If one considers incidence data as more appropriate than mortality data, three of the 4 cohort studies present statistically increased risks, and the fourth did not have enough power and also presented an increased risk [Matanoski et al., 1991]. Among the six case-control studies, three had more than 10 cases of breast cancer in a given job title, and two of the 3 presented significant increases [Demers et al., 1991; Coogan et al., 1996b].

    Organochlorine compounds: There are about 15,000 organochlorine compounds, many of these persist in the environment, and some do not [Adami et al., 1995]. These compounds include products that are no longer used (e.g. polychlorinated biphenyls, or PCBs, in electric capacitors and transformers; certain pesticides such as DDT, heptachlor, mirex), and some that still occur as inadvertent contaminants (e.g. dioxins, including TCDD, and furans). The popularized hypothesis linking breast cancer to organochlorines deals not with occupational exposure but to dietary and environmental exposures [Adami et al., 1995]. The focus here will be on occupational exposures, as for the rest of the review.

    Only one descriptive study reported risk estimates for exposure to PCBs or insecticides, stating inconclusive results [Cantor et al., 1995]. Two occupational cohort studies (Table 2) found no increase in the breast cancer mortality risk among female workers exposed to PCBs [Brown et al., 1987; Bertazzi et al., 1987], and Adami et al. [1995] calculated a summary estimate of 0.84 (95% CI=0.50-1.33), based on a total of 18 cases from 4 studies, of which two had not been published. A cohort of male electric utility workers exposed to PCBs was not conclusive [Loomis et al., 1997]. An international cohort study of workers exposed to phenoxy herbicides, chlorophenols and dioxins, from 36 different cohorts, found elevated risks for workers exposed to TCDD [Kogevinas et al., 1997]. The latter concluded that the excess mortality from breast cancer was restricted to one cohort of female workers from Germany (9 cases; SMR=2.84, 95% CI=1.30-5.39); the cohorts from the other countries did not experience increased mortality from breast cancer. The risk was also somewhat elevated among males, based on 2 cases (SMR=2.56, 95% CI=0.31-9.26) [Kogevinas et al., 1997]. A meta-analysis of the TCDD studies produced a summary estimate for female breast cancer of 1.08 (95% CI=0.68-1.58), based on 24 cases [Adami et al., 1995].

    To our knowledge, no case-referent study has been published so far on occupational exposure to organochlorine compounds and breast cancer in women or in men. The available case-control studies compare serum and fat cells content of organochlorines and their metabolites, especially DDT, DDE and PCBs, in cases of breast cancer and in other women [Falck et al., 1992; Wolff et al., 1993; Dewailly et al., 1994; Krieger et al., 1994; Hunter et al., 1997; Lopez-Carrillo et al., 1997; van't Veer et al., 1997]; they can possibly be seen as indirect evidence for an occupational association. So far, the studies produced inconsistent results, more recent studies of larger sample size showing no association [Krieger et al., 1994; Hunter et al., 1997; Lopez-Carrillo et al., 1997; van't Veer et al., 1997]. There are several on-going studies on this issue, and two from Canada should be published shortly [personal communication with Dr. K. Aronson].

    Farmers and gardeners: Seven descriptive studies reported figures for breast cancer risks in relation to farmers: in three of them, there was a significantly reduced risk for females [Kato et al., 1990; Ronco et al., 1992; Wiklund and Dich, 1994], whereas in three others the risks were slightly reduced or close to unity for females [Rubin et al., 1993; Blair et al., 1993; Morton, 1995] and slightly elevated for nonwhite males (4 cases; PMR=1.72, 95% CI=0.46-4.41) [Blair et al., 1993]; in the last one, there was an increased risk of 1.15 among nonwhite females [Austin et al., 1995]. Four cohort studies were found (Table 2), two of them, from Norway and Finland, showing a statistically significant reduction in risk among female farmers (148 cases; SIR=0.84, 95% CI=0.72-0.99) [Kristensen et al., 1996] and 1,474 cases; SIR=0.77, 95% CI=0.73-0.80) [Pukkala and Notkola, 1997]) and a non significant reduction among male farmers or agricultural employees (4 cases; SIR=0.65, 95% CI=0.18-1.51 [Kristensen et al., 1996]/ 11 cases; SIR=0.72, 95% CI=0.36-1.28 [Pukkala and Notkola, 1997]/ 5 cases; SIR=0.48, p>0.05 [Ronco et al., 1992]), while one showed risks close to unity for females [Folsom et al., 1996]. A cohort studying Danish gardeners also found a risk of about one (10 cases among women, no cases among men; SMbR=1.07, 95% CI=0.51-2.11) [Hansen et al., 1992]. A large prospective cohort study of farmers and their families is underway in Iowa and North Carolina (The Agricultural Health Study) [Alavanja et al., 1994] but results are not expected for a few more years. A case-control study reported decreased risks for women in the broad occupational activity of farming, forestry and fishing [Coogan et al., 1996a]. Finally, an Italian multi-site case-control study showed breast cancer risks close to unity among female farmers and did not report any case among males [Franceschi et al., 1993].

    Clerical and professional (other than health services workers): Numerous studies based on administrative data (descriptive studies) reported associations of female breast cancer (incidence or mortality) with clerical and professional jobs, and for a few occupational categories, the number reporting statistically significant excess risks was rather impressive: white collar, professional and managerial occupations, clerical, secretarial, and related jobs, teachers, scientists, and clergy [Doebbert et al., 1988; Bulbulyan et al., 1992; Aronson and Howe, 1994; Katz, 1983; King et al., 1994; Roman et al., 1985; Dosemeci and Blair, 1994; Rubin et al., 1993; Seniori Costantini et al., 1994; Olsen and Jensen, 1987; Kato et al., 1990; Lynge and Thygesen, 1990; Belli et al., 1992; Zheng et al., 1993; Morton, 1995].

    In eight cohort studies involving industrial populations [Bond et al., 1987; Thomas and Decoufle, 1979; Monson and Nakano, 1976; Delzell and Monson, 1981; Béral et al., 1985; Carpenter et al., 1994; Smith et al., 1986; Vaughan et al., 1993; Steenland et al., 1991; Goldberg and Thériault, 1994], female breast cancer risks for a variety of administrative and secretarial or clerical occupations were not greater than expected. By contrast, a cohort study of the workforce in a large chemical plant showed and increased incidence of breast cancer among female salaried employees, most of whom were clerical, technical and professional personnel [Pell et al., 1978; O'Berg et al., 1987]. In addition, a cohort study of female municipal workers did not reveal any associations for professional, clerical and service employees [Vena and Petralia, 1995].

    In one case-control study using main lifetime occupation [Williams et al., 1977], excess risks were observed for clerical workers (335 cases; OR=1.25, p<0.05) and for persons employed in the insurance industry (38 cases; OR=2.83, p<0.05), but significant negative associations were also reported for individuals working in professional and related services (33 cases; OR=0.59, p<0.05), and managers and administrators (39 cases; OR=0.55, p<0.01). In another case-control study designed to study hormone replacement therapy, an increased risk was found for receptionists (24 cases; RR=1.9, 95% CI=1.0-4.0), after controlling for age, parity, education, alcohol intake and body size [Habel et al., 1995]. In the last case-control study, also designed for other purposes, a significantly increased risk of 1.18 (95% CI=1.09-1.27) was found for administrative support occupations, including clerical [Coogan et al., 1996a].

    In view of the fact that exposures to specific occupational agents cannot be identified easily in most of these occupational groups, interpretation of the results is delicate. The excess risks reported for these occupations may have been confounded by reproductive factors, there are no estimates of risk by duration of employment, and there are no obvious occupational exposures.

    Nurses and other health personnel: Health professionals are of considerable interest because they may be exposed to a wide variety of agents, including anaesthetic gases, chemotherapy drugs and organic solvents. However, heterogeneity of occupational exposures complicates the interpretation of associations and pooling large groups of professionals for analysis may dilute the risks. A few administrative studies showed excess risks among nurses, physicians and other health professionals [Doebbert et al., 1988; Bulbulyan et al., 1992; Katz, 1983; King et al., 1994; Roman et al., 1985; Rubin et al., 1993; Olsen and Jensen, 1987; Lynge and Thygesen, 1990; Sankila et al., 1990; Morton, 1995]. Results from earlier cohort studies have been mostly inconclusive for nurse-anesthetists [Corbett et al., 1973], dentistry workers [Cohen et al., 1980], and operating room personnel [Cohen et al., 1974]; one more recent longitudinal study of nurses did not report increased breast cancer risks with respect to the general population [Hunter et al., 1990], but another one showed increasing incidence with duration of follow-up: the standardised incidence rate (SIR) went from 1.3 (95% CI=0.89-1.75) to 3.3 (95% CI=1.21-7.18) for 10 to 50 years between first employment and date of the study [Gunnarsdóttir and Rafnsson, 1995]. Lastly, a cohort study of scientists, laboratory technicians and maintenance workers [Belli et al., 1992] showed a significant increase in the risk of dying from breast cancer (8 cases; SMR=2.88, 95% CI=1.24-5.68). A case-control study designed to investigate the effect of hormone replacement therapy did not find an increased risk for nurses, other health treatment workers, health care assistants and other health technicians, after controlling for reproductive risk factors [Habel et al., 1995]. Another case-control study, investigating an array of dietary and lifestyle risk factors, also presented similar results on breast cancer risk among nurses and other health services occupations [Coogan et al., 1996a].

    Cosmetologists, hairdressers, and beauticians: It is likely that cosmetologists and related workers are exposed to a number of potentially toxic agents, such as hair dyes, organic solvents (in nail products, settings, and hair sprays), and detergents. The International Agency for Research on Cancer (IARC) has classified occupational exposures of haidressers or barbers as probably carcinogenic to humans [IARC, 1993]. Four administrative studies detected significantly elevated relative risks of breast cancer among these workers, ranging from 1.2 to 1.9 [Doebbert et al., 1988; Kato et al., 1990; Lynge and Thygesen, 1990; Morton, 1995]. Of the four cohort studies investigating female cosmetologists, two incidence studies showed increased risks: one found an SIR=1.27 (86 cases; 95% CI=1.01-1.57) among cosmetologists licensed between 1925 and 1934 [Teta et al., 1984], and the other showed a SIR=1.31 (70 cases; 95% CI=1.02-1.65) among female hairdressers during the period of 1970 to 1987 [Pukkala et al., 1992]; the two last studies showed inconclusive results that may be due to low statistical power [Kono et al., 1983; Gubéran et al., 1985]. Two case-control studies designed to look at other risk factors than occupation did not find increased risks for hairdressers, cosmetologists and beauticians together [Habel et al., 1995; Coogan et al., 1996a]. However, in one case-control study designed specifically to look at breast cancer in relation to hair dyes use [Koenig et al., 1991], a relative risk of 3.0 (95% CI=1.1-7.8) was observed among beauticians employed for five or more years; personal use of hair dyes was not associated with breast cancer risk in that study.

    Pharmaceutical industry: A range of studies are available here: pharmacy technicians are not likely to be exposed to the same extent as pharmaceutical manufacturing workers are. Types of exposures also vary, and it is plausible that occupational exposure to sex hormones, espacially during the manufacturing process, can modify the breast cancer risk through a modification in the hormonal balance, both in males and in females. One study based on administrative data showed an excess risk among black women working in the pharmaceutical industry (RR=1.64, p<0.05) [Hall and Rosenman, 1991]. Positive associations were observed in two cohort studies of pharmaceutical workers, with a SMR of 1.79 (22 cases; 95% CI=1.12-2.71) [Thomas and Decoufle, 1979], and a SIR=1.5 (97 cases; 95% CI=1.2-1.8) [Hansen et al., 1994]. There was a suggestion that incidence rates increased by length of service among workers involved in the manufacture of insulin, antibiotics, enzymes, sex hormones and other synthetic drugs, especially among women who started working aged 30 to 39 [Hansen et al, 1994]. The same study showed a clear excess of male breast cancer with a SMR of 7.0 (3 cases; 95% CI=1.5-21.4 ) [Hansen et al., 1994]. No association was observed in the investigation of female pharmacy technicians [Hansen and Olsen, 1994], or reported in the case-control studies [Habel et al., 1995; Coogan et al., 1996a].

    Radiation workers and x-ray technicians: Although ionizing radiation is a recognized risk factor for breast cancer [Committee on the Biological Effects of Ionizing Radiation, 1990], the low cumulative radiation doses experienced by x-ray technicians and atomic energy workers, the imprecision of measurements in most studies, the somewhat short follow-up and other confounders and biases could all explain the absence of positive findings so far.

    Excluded from consideration here were studies of the female radium dial painters because they have limited relevance to occupations post World War II. No descriptive study reported increased breast cancer risk among radiation workers and x-ray technicians. Seven cohort studies have presented results on radiation workers, including diagnostic x-ray personnel [Wang et al., 1988], workers at nuclear materials production plants [Hadjimichael et al., 1983; Loomis and Wolf, 1996], a thorium-processing plant [Liu et al., 1992], United Kingdom Atomic Energy Authority plants [Béral et al., 1985; Carpenter et al., 1994], the Sellafield reprocessing plant [Smith and Douglas, 1986], and United States nuclear plants [Vaughan et al., 1993; Kneale and Stewart, 1993; Frome et al., 1997]. These workers had experienced various exposure levels, and some of them had radiation to the whole body as well as exposure to radionuclides, usually at low doses. Only one of these occupational studies showed a statistically significant excess risk, among Chinese x-ray workers exposed for more than 20 years and who started working before 1950 [Wang et al., 1988]. However, most of the other studies were not powerful enough; two studies showed elevated risks: SIR=3.1 (3 cases; 95% CI=0.7-9.7) [Vaughan et al., 1993], SMR=1.21 (11 cases; 95% CI=0.60-2.17) [Loomis and Wolf, 1996]. A recent case-control study, conducted among female radiologic technologists in the U.S.A. [Boice et al, 1995; Morin Doody et al., 1995], did not show any increased risk of breast cancer in that population; their cumulative exposure was reported to be low. The two case-control studies designed for other purposes also did not find increased risks for these workers [Habel et al., 1995; Coogan et al., 1996a].

    General chemical exposures: Two descriptive studies showed increased risks of breast cancer among chemists [Hall and Rosenman, 1991; Morton, 1995]. Two cohort studies reported higher than expected risks among chemists, with considerably higher risks noted in single women (30 deaths; MOR=2.3, 95% CI=1.5-3.5) [Walrath et al., 1985], and a five-fold risk among 36 laboratory workers (7 deaths; MOR=5.3, 95% CI=2.8-10.1) [Dosemeci et al., 1992]. Cohort studies of female workers from three large chemical companies in the U.S.A. showed increased incidence in one with a SIR=1.33 (256 cases; p<0.05) among salaried employees [Pell et al., 1978; O'Berg et al., 1987], and non-significant increase of death in the two others with SMRs of 1.22 (46 cases; 95% CI=0.89-1.63) [Bond et al., 1987] and of 1.0 (39 cases; 95% CI=0.7-1.4) [Teta et al., 1990]. A small Italian cohort study of 505 chemical workers was also not conclusive for male breast cancer, but the authors underlined the low statistical power of their study [Rapiti et al., 1997].

    Specific chemical exposures have been investigated, with a lack of association reported for women exposed to chlorinated naphthalenes in the cable manufacturing industry (SMR=1.0, 95% CI=0.7-1.3) [Ward et al., 1994] and to formaldehyde [Blair et al., 1986; Stayner et al., 1988]. One cohort study of workers exposed to ethylene oxide obtained a SMR=0.8 (42 cases; 95% CI=0.6-1.1) [Steenland et al., 1991], whereas an incidence cohort study showed a two-fold increase in breast cancer incidence (8 to 12 cases; standardised morbidity ratio or SMbR=1.7 to 2.6, 95% CI=0.99-4.98, depending on the methods of calculation used) [Norman et al., 1995]. In a case-control study among members of the Kaiser Permanente Medical Care Program, a positive association (2507 cases; RR=1.53, 95% CI=1.00-2.33) was observed among women reporting occupational daily exposure (at least 2 hours) during the past year to engine exhaust [Van Den Eeden and Friedman, 1993].

    Rubber and plastics workers: Several cohort studies focusing on mortality have been published since the mid-seventies on rubber manufacturing workers, both female and male. Unfortunately, most of these studies investigated mortality only, and almost all of them had very little power to detect an increase in risk. None of these reported increased risks of breast cancer [Monson et al., 1976; Delzell and Monson, 1981; Andjelkovich et al., 1978; Gustavsson et al., 1986; Zhang et al., 1989; Sorahan and Pope, 1993b; Weiland et al., 1996]; Solionova and Smulevich [1993] reported a significant deficit of incidence of breast cancer in their cohort (8 cases; SIR=0.47, p<0.05). Finally, an Italian study presented elevated risks (2 deaths; non significant SMR= 1.86) among a cohort constituted by workers from 20 rubber and plastics factories [Ietri et al., 1997]. Mortality cohort studies of workers in polyvinyl fabrication [Chiazze et al., 1980], polyurethane foam manufacturing [Hagmar et al., 1993; Sorahan and Pope, 1993a; Schnorr et al., 1996], in cellulose fiber production [Lanes et al., 1990; Lanes et al., 1993; Gibbs et al., 1996] and in continuous filament fiberglass production [Watkins et al., 1997], did not report increased risks of breast cancer.

    Wood and pulp and paper: Of the four mortality cohort studies among workers in wood-related industries, three did not find an increased risk of female breast cancer [Jäppinen et al., 1989; Demers et al., 1995; Robinson et al., 1996], and one presented an elevated risk of 3.4 (4 deaths; 95% CI=0.9-8.8) among nonwhite women working in wood furniture plants [Miller et al., 1994]. An elevated PMR of 5.1 (4 cases; 95% CI=1.39-13.1) was found among wood products carpenters employed in the construction or wood products industries [Robinson et al., 1996]. One cohort study in the Spanish pulp and paper industry showed an elevated risk of female breast cancer of 2.84 (95% CI=0.77-7.32) based on 4 deaths [Sala-Serra et al., 1996], and two others showed a lower risks [Jäppinen et al., 1987; Coggon et al., 1997]. Again, most of the studies looked here at mortality from breast cancer.

    Organic solvents: Organic solvents are ubiquitous both in the environment and in the workplace. They take part in the manufacture of glues, paints, varnishes, various chemicals, and are used notably in dry cleaning and metal degreasing. A study on solvent exposure and mental disorders among males in Montreal showed that 57% of the control population had ever been exposed to organic solvents at work [Labrèche, 1989]. Many descriptive studies based on administrative records have suggested increased risks for certain occupations that may involve exposures to solvents, namely printing and publishing [Lynge & Thygesen, 1990; Hall & Rosenman, 1991; Aronson & Howe, 1994] and mechanics and repairers [Rubin et al., 1993]. No descriptive study of laundry and dry cleaning workers showed increased risks for female breast cancer [Katz and Jowett, 1981; Duh and Asal, 1984; Lynge and Thygesen, 1990; Walker et al., 1997], but one showed an increase of breast cancer among men aged 65 and over (4 deaths; PMR=12.75, 95% CI=3.47-32.63) [Walker et al., 1997].

    The analytic epidemiologic data are rather sparse (Table 3). The laundry and dry cleaning industry has used several organic solvents over the years. Stoddard solvent was used until the 1930s, followed by carbon tetrachloride, and then trichloroethylene, fluorocarbons, and tetrachloroethylene or perchloroethylene), the latter being the most prevalent nowadays [Brown and Kaplan, 1987; Blair et al., 1990]. The two available cohort studies, both focusing on mortality, were inconclusive for exposure to perchloroethylene [Brown and Kaplan, 1987; Ruder et al., 1994], or to a mixture of solvents, including Stoddard solvent, tetrachloroethylene, trichloroethylene, and fluorocarbons [Blair et al., 1990]. No case-control study showed increased risk for these workers.

    A mortality cohort study of aircraft maintenance workers exposed to trichloroethylene was consistent with the null results from the studies of dry cleaners [Spirtas et al., 1991]. An elevated risk was observed, however, among white women for exposure to isopropyl alcohol (number of cases not reported; SMR=3.12, 95% CI=1.25-6.43). Axelson and coworkers [1994] also investigated cancer incidence and mortality in trichloroethylene exposed workers, but they provided no risk estimate for cancer of the breast for males or females, and one assumes that very few cases were observed. Women employed in coiling and wire drawing in the manufacturing of light bulbs had an excess of breast cancer incidence among those who worked more than 5 years in the coiling and wire drawing department (8 cases; SIR=3.23, 95% CI=1.05-7.53) [Shannon et al., 1988]; methylene chloride and trichloroethylene were the two solvents used.

    One cohort study of female shoe manufacturers showed no increased risk of death from breast cancer [Paci et al., 1989], and three others did not present figures for breast cancer among their workers [Garabrant et al., 1984; Walker et al., 1993; Fu et al., 1996]. Two cohort studies of leather tannery workers showed risks between 20% and 50% above expected: in Sweden, Mikoczy and coworkers [1994] found incidence rates to be elevated for workers with at least 20 years since the first exposure (19 cases; SIR= 1.47, 95% CI=0.90-2.33), and in Italy, the mortality risks were at 1.25 (6 cases; 95% CI=0.46-2.73) [Montanaro et al., 1997]. No association for mortality was observed among styrene-exposed workers [Wong, 1990; Kogevinas et al., 1994; Wong et al., 1994], among a cohort of benzene-exposed Chinese women [Yin et al., 1996], among two cohorts of workers exposed to methylene chloride [Lanes et al., 1993; Gibbs et al., 1996], and among workers regularly monitored in Finland, for exposure to organic solvents [Anttila et al., 1995]. Danish printing workers had an increased incidence of female breast cancer (88 cases; SIR=1.35, 95% CI=1.08-1.66), especially among the bookbinders' assistants (48 cases; SIR=1.57, 95% CI=1.16-2.08) [Lynge et al., 1995]. A mortality follow-up study of oil refinery workers showed slightly higher risks among white women (20 cases; SMR=1.34, 95% CI=0.82-2.07) [Satin et al., 1996].

    Workers in the industries of newspaper printing (7 cases; SIR=3.9, p<0.01) and soap and perfume making (3 cases; SIR=7.6, p<0.05) had a higher risk of developing breast cancer in a Swedish case-control study [McLaughlin et al., 1988]. One case-control study reported a modest increase in incidence among females in the occupational group of painters, sculptors and printmakers (5 cases; RR=1.7, 95% CI=0.4-7.4) [Habet et al., 1995], and another one, a small increase among precision production occupations (128 cases; OR=1.26, 95% CI=0.98-1.62) [Coogan et al., 1996a].

    Physical exercise: Six case-control studies on female breast cancer applied ratings of physical activity to job titles information already collected: five of them reported a significant decreasing trend of breast cancer risk among women as they performed more active physical activities in their job [Vena et al., 1987; Vihko et al., 1992; Zheng et al., 1993; D'Avanzo et al., 1996; Coogan et al., 1997]; the last case-control study did not find any effect of increased physical activity on breast cacner risks [Dosemeci et al., 1993].

    Other occupations: Two other occupations have been associated to an increased risk among females: airline cabin attendants, in one record linkage cohort study (20 cases; SIR=1.87, 95% CI=1.15-2.23) [Pukkala et al., 1995], and professional artist painters in a proportional mortality study, based on 16 deaths (PMR=2.16, p< 0.01) [Miller and Blair, 1985]. Among males, the following occupations have been associated with elevated risks: the military service, with 16 cases on 52 compared to 6 controls on 52 serving in the military forces (p=0.06) [Mabuchi et al., 1985]; and Danish paper recycling workers with a non significantly increased incidence, based on 1 case (SIR= 2.63, 95% CI=0.03-14.64) [Andreassen Rix et al., 1997].

    Other exposures: In a case-control study of male breast cancer (52 cases and 52 controls), Mabuchi et al. [1985] found 7 male cases working in blast furnaces, steel works and rolling mills, whereas no control worked in such industries (p=0.016); they hypothesized a possible testicular effect of high environmental temperature to explain that finding. A small case-control study of male breast cancer found an elevated risk for heat-exposed jobs, based on 9 exposed cases (OR=2.3, 95% CI=0.95-5.3) [Rosenbaum et al., 1994]. Exposure to arsenic at a copper smelter was not related to an increased risk of death from male breast cancer in an American cohort study [Enterline et al., 1995].

    Discussion and recommendations

    Male and female breast cancers have very similar histopathologic features and share a few risk factors (such as age and family history of breast cancer in a first degree relative); mortality rates appear stable for both genders over the last 25 years [Sasco et al., 1993; National Cancer Institute of Canada, 1993]. However, their pattern of incidence differs in that it has not changed in males over the last decades, whereas it increased by 28% in Canadian females. This change of incidence among females together with their increased participation in the workplace, and the resulting different exposures, imply that causes may differ between genders or that at least changes in exposures have varied differently for males and females over the last decades.

    As stated earlier, we relied whenever possible on information from analytical (cohort and case-control) studies, that we considered to be more robust than the descriptive studies. But because few studies were designed specifically to investigate breast cancer risks, the limitations inherent in these studies must be recognized when interpreting the data. In particular, statistical power and risk estimates would have been reduced in mortality studies in which broad occupational groups were used as surrogates of exposure. As well, statistical power was generally quite low for assessing trends or for assessing risks in sub-groups. In addition, confounders were usually not taken into account in cohort studies and inference from these studies would be stronger if they had been controlled for.

    With regard to the assessment of exposure, one would expect in cohort studies that misclassification would be less pronounced than in studies using routinely collected data because job titles from plants should be more homogeneous for exposure. Nevertheless, exposures were ascertained in only a handful of studies. There were few cohort studies in which exposures were assessed directly or which analyses were conducted by job title. In the case-control studies, while detailed information regarding occupational lifetime histories were obtained directly from subjects, broad occupational groupings were reported in the analyses, but they had the advantage of adjusting for the major confounding factors.

    Selection into and out of work among subjects enrolled in cohort studies (i.e. the healthy worker effect) may also have led to underestimation of risks. It is difficult to control for these effects, although partial control of selection into the cohort can be achieved through the use of internal reference groups. However, no study reported such analyses for breast cancer, although they were carried out for other endpoints in a number of studies.

    It is clear from this review that few high quality studies directed specifically toward assessing occupational breast cancer risks, both among males and females, have been carried out to allow one to identify unambiguously occupational risk factors for breast cancer. The fact that the cohorts of women were generally small is understandable, as few women would have been working in hazardous employment during the period covered by many of these retrospective studies, even though women have been taking an increasingly active part in the workforce since World War II. The quality of studies has increased over the years, and the recent ones provide better adjusted figures. More detailed investigations are being carried out and more information is expected in the coming years.

    Future occupational studies should preferably focus on incidence data as the 5-year survival rates for breast cancer are around 75% [Pelletier, 1996]. They should rely as much as possible on histologically confirmed cases and even consider the estrogen and progesterone receptor status of the tumors, as recent studies have shown differing risk factors, treatment and prognostic features according to these tumor characteristics. Future studies should always take into account menopausal status for female breast cancers, as known risk factors are distributed differently for pre- and post-menopausal breast cancers and etiologic mechanisms could vary accordingly. More effort has to be put to refine the indicators of occupational exposures, e.g. job-exposure matrices, industrial hygiene measurements and estimates, and biological markers of exposure, and to design studies that allow for exposure-response analyses.

    As breast cancer is considered to be an hormone-related cancer and although many areas would benefit from more research, areas where workers are exposed to substances or circumstances susceptible to disrupt hormonal balance are probably among the most promising ones. Some examples are:

    - electromagnetic fields and night work (both affecting melatonin synthesis) could possibly exert a promoting effect; more effort should be put into quantifying the exposure levels and monitoring the size of the effect of these exposures (possibly using biomarkers such as melatonin);

    - organochlorines, pharmaceutical drugs and possibly some metals such as cadmium could indirectly increase the risk via estrogenic effects.

    As well, a few occupations entailing exposures that vary considerably within the same job title, e.g. nurses, chemical workers, etc., would be worth exploring in detail. Given the capacity of the breast, especially among women, to secrete fluids and accumulate xenobiotics, it would also be warranted to explore occupations with exposures to chemicals metabolised into reactive chemicals such as organic solvents and rubber and plastic chemicals [Labrèche and Goldberg, 1997].

    Table 1 Risks of breast cancer in relation to occupations with potential exposure to extremely low frequency electromagnetic fields


    Reference

    Country

    Type of study

    Adjustment for risk factors

    Occupation / industry / exposure
    Cohort= power*/ Case-control = total number of cases
    Observed number of cases

    Risk

    95% Confidence interval or p value
    Vågerö et al., 1985 Sweden Cohort (2047% / 867 &)
    Mortality
    Age and sex Telecommunication workers %: NA**

    &: 75.5%
    0 %

    7 &
    SMR=NA

    SMR=0.6
    NA

    0.3-1.3
    Matanoski et al., 1991 USA (1 State) Cohort (50,582 %)
    Incidence
    Age, dose of EMFs Telephone workers %: 2.5% 2 % SIR=6.5 0.79-23.5
    Tynes et al., 1992 Norway Cohort (37,945 %)
    Incidence
    Age Electrical workers (1961-85) %: 49.4% 12 % SIR=2.07 1.07-3.61
    Floderus et al., 1994 Sweden Cohort
    Incidence
    Age, dose of EMFs Railway workers (1961-69)
    Engine drivers (1961-69)
    %: 8.4%
    %: 5.4%
    4 cases
    3 cases
    RR=4.9
    RR=4.3
    1.6-15.7
    1.6-11.8
    Thériault et al., 1994 Québec, Ontario, France Cohort
    Case-control analysis
    Age Electric utility workers
    $15.7:T-years

    443 cancer cases

    7 cases

    OR=0.85

    NR
    Savitz & Loomis, 1995 5 places in the USA Cohort (138,905 %)
    Mortality
    Age Electric utility workers %: 63.7% 6 cases SMR=0.8 0.29-1.74
    Tynes et al., 1996 Norway Cohort (2,619 &)
    Incidence
    Case-control within cohort
    Age Female radio and telegraph operators on merchant ships
    >50 years old &
    > 3.2 years of employment
    Lot of shiftwork
    Lot of shiftwork before 30
    &: 99.7% 50 cases


    15 cases
    12 cases
    8 cases
    SIR=1.5


    OR=5.9
    OR=6.1
    OR=4.6
    1.1-2.0


    0.7-47.7
    1.5-24.2
    1.3-17.1
    Demers et al., 1991 6 States + Detroit (MI), San Francisco (CA), Atlanta (GA), Seattle (WA) Case-control
    Incidence
    Age, Jewish religion,higher education, diagnostic x rays, serious head injury, Quetelet index Males probably exposed to EMFs (based on previously published list)
    Electric trades & related occupations
    227 breast cancers, 300 population controls 33 cases

    13 cases
    OR=1.8

    OR=6.0
    1.0-3.7

    1.7-21
    Loomis, 1992 USA, 24 States Case-control
    Mortality
    Age Electrical workers < 65 years
    Telephone workers
    250 % breast cancers 3 cases
    1 case
    OR=2.2
    OR=9
    0.6-7.8
    0.9-88.7
    Rosenbaum et al., 1994 New York State Case-control
    Incidence
    Age, race, marital status, address Occupations probably exposed to EMFs (based on previously published list) 63 % breast cancers 6 cases OR=0.7 0.3-1.9
    Habel et al., 1995 King County, WA Case-control
    Incidence
    Age, parity, education, alcohol intake, Quetelet index Telephone and other communication operators 536 breast cancers 22 cases OR=0.8 0.4-1.4
    Coogan et al., 1996b 4 States: Maine, Wisconsin, Massachusetts, New Hampshire Case-control, females
    Incidence
    Age, Quetelet index,benign breast disease, family history of breast cancer, age at menarche, parity, age at 1st birth, education, alcohol intake Occupations probably exposed to EMFs (based on previously published list)
    Pre-menopausal + high expo.

    Computer equipment operators (pre & post-menopausal)
    698 breast cancers probably exposed


    20 cases

    31 cases



    OR=1.98

    OR=1.79



    1.04-3.78

    1.03-3.11
    Stenlund & Floderus, 1997 Sweden Case-control, males
    Incidence
    Age, education, solvent exposure, family history of breast cancer, cryptorchidism Occupations probably exposed to EMF,
    $0.41:T

    # 60 years old, $0.41:T
    56 breast cancers

    4 cases

    3 cases


    OR=0.7

    OR=1.5


    0.2-2.3

    0.3-8.3

    * Power calculations were performed for a Poisson distribution, considering a detectable risk of 2, by George Tomlinson, PhD candidate, University of Toronto
    ** NA = Not applicable / NR: Not reported / SMR: Standardised mortality ratio / SIR: Standardised incidence ratio / RR=relative risk / OR=odds ratio

    Table 2. Risks of female breast cancer in relation to potential occupational exposure to pesticides and organochlorines


    Reference

    Country

    Type of study

    Adjustment for risk factors

    Occupation / industry / exposure
    Cohort= power*/ Case-control = total number of cases Observed number of cases
    Risk**
    95% Confidence interval or p value
    Kogevinas et al., 1997 12 countries Cohort (20,851 % / 1,012 &) Age, country of residence Production, formulation and spraying of TCDD or higher chlorinated dioxins %: 7.3%

    &: 32.6%
    2 %

    9 &
    SMR=2.56

    SMR=2.16
    0.31-9.26

    0.99-4.01
    Kristensen et al., 1996 Norway Cohort (2,145 &, of which 590 farmers) Age, details on exposure Agricultural workers 100%

    100%
    598 &

    148 & farmers
    SIR=1.05

    SIR=0.84
    0.96-1.13

    0.72-0.99
    Pukkala & Notkola, 1997 Finland Cohort (106,162 % / 81,431 &) Age, type of farm Farmers %: 90.4%

    &: 100%
    11 %

    1,474 &
    SIR=0.72

    SIR=0.77
    0..36-1.28

    0.73-0.80
    Hansen et al., 1992 Denmark Cohort (3,156 % / 859 &) Age, type of work Gardeners %: NA

    &: 68.4%
    0 %

    10 &
    --

    SIR=1.07


    0.51-2.11
    Folsom et al., 1996 Iowa Cohort Age, reproductive factors, lifestyle Women living on farms 100% 179 & RR=1.03 0.87-1.23
    Brown, 1987 New York, USA Cohort (1,318 &) Age Workers in electrical capacitor plants / PCBs 78.5% 9 & SMR=0.77 0.35-1.46
    Bertazzi et al., 1987 Italy Cohort (1,556 &) Age Electrical capacitor manufacturing workers / PCBs 20.9% 2 & SMR=1.01 0.11-3.63
    Coogan et al., 1996a 4 States: Maine, Wisconsin, Massachusetts, New Hampshire Case-control Age, reproductive factors, lifestyle Women employed in farming, forestry, fishing 6,835 cases 94 & OR=0.81 0.62-1.07
    Franceschi et al., 1993 Italy Case-control Age, reproductive factors, lifestyle, diet, etc. Farmers 132 cases 26 & OR=0.8 0.5-1.3

    * Power calculations were performed for a Poisson distribution, considering a detectable risk of 2, by George Tomlinson, PhD candidate, University of Toronto

    ** SMR: Standardised mortality ratio / SIR: Standardised incidence ratio / RR=relative risk / OR=odds ratio

    Table 3 Relative risks of breast cancer in occupations or industries with organic solvent exposure


    Reference

    Country

    Type of study

    Adjustment for risk factors

    Occupation / industry / exposure
    Cohort= power*/ Case-control = total number of cases
    Observed number of cases

    Risk**

    95% Confidence interval or p value
    Chiazze et al., 1977, 1980 USA Cohort
    Mortality
    (NR*)

    Polyvinylchloride fabricators Vinyl chloride NA 44 PMR=1.8 p> 0.05
    Stayner et al., 1985, 1988
    Cohort
    Mortality
    (9022)

    Garment industry Formaldehyde 100% 33 SMR=0.7 0.5-1.0
    Brown & Kaplan, 1987; Ruder et al., 1994 4 cities in California, Illinois, Michigan, New York Cohort
    Mortality
    (1109)

    Dry cleaning
    -Entire cohort
    -Tetrachloroethylene + other solvents (695)
    -Tetrachloroethylene (414)

    92.0%
    79.8%

    53.8%

    19
    13

    6

    SMR=1.1
    SMR=1.1

    SMR=1.0

    0.7-1.7
    0.6-1.9

    0.4-2.2
    Shannon et al., 1988 Toronto, Ontario Cohort
    Incidence
    (1044)

    Lamp manufacturing Methylene chloride, trichloroethylene
    - Total cohort in coiling/ wire drawing (203)
    - 5 years work, 15 years latency


    40.8%

    20.5%
    21

    8

    5
    NR

    SIR=2.0

    SIR=3.2
    NR

    0.9-4.0

    1.1-7.5
    Paci et al., 1989 Firenze, Italy Cohort
    Mortality
    (1005)

    Shoe manufacturing Benzene and other solvents 38.6% 4 SMR=0.9 0.2-2.3
    Blair et al., 1990 Missouri, USA Cohort
    Mortality
    (4046)

    Dry cleaners Tetrachloroethylene and other solvents 99.8% 36 SMR=1.0 0.7-1.4
    Wong et al., 1990, 1994 USA Cohort
    Mortality
    (3868)

    Reinforced plastics and composites industry Styrene 97.7% 14 SMR=0.6 0.3-1.1
    Spirtas et al., 1991 Utah, USA Cohort
    Mortality
    (3138)

    Aircraft maintenance
    -Mixed solvents
    -Trichloroethylene
    -Isopropyl alcohol
    -Methylene chloride
    99.9
    79.8%
    NA
    NA
    30
    9
    NR
    3
    SMR=0.7
    SMR=0.8
    SMR=3.1
    NR
    0.5-1.0
    0.4-1.5
    1.3-6.4
    P2=6.2, p=0.01
    Lanes et al., 1993 South Carolina, USA Cohort
    Mortality

    Cellulose fiber production workers / Methylene chloride
    3 cases SMR=0.54 0.11-1.57
    Kogevinas et al., 1994 Denmark, Finland, Italy, Norway, Sweden, United Kingdom Cohort
    Mortality (6128)

    Styrene exposed workers 98.8% 13 SMR=0.5 0.3-0.9
    Mikoczy et al., 1994 Sweden Cohort
    Incidence
    (482)

    Leather tanning: Benzene & other chlorinated solvents
    No latency period
    Latency 20 years


    87.4%
    83.4%


    20
    19


    SIR=1.3
    SIR=1.5


    0.8-2.0
    0.9-2.3
    Anttila et al., 1995 Finland Cohort
    Incidence
    (1924)

    Workers exposed to halogenated solvents Trichloroethylene,
    Tetrachloroethylene, 1,1,1-Trichloroethane
    99.9% 34 SIR=0.9 0.6-1.2
    Yin et al., 1996 China Chort
    Mortality
    (59,628 %,
    51,005 &)

    Benzene-exposed workers
    8 cases RR=0.9 0.3-3.2
    Montanaro et al., 1997 Genoa, Italy Cohort
    Mortality

    Tannery workers
    6 % & & SMR=1.25 0.46-2.73
    Habel et al., 1995 Washington State, USA Case control
    Incidence

    Painters, sculpters, printmakers Various solvents 537 cases &
    487 controls
    5 cases &
    3 controls
    RR=1.7 0.4-7.4
    Coogan et al., 1996a 4 States: Maine, Wisconsin, Massachusetts, New Hampshire Case-control
    Incidence

    Precision production workers
    128 cases OR=1.26 0.98-1.62

    * Power calculations were performed for a Poisson distribution, considering a detectable risk of 2, by George Tomlinson, PhD candidate, University of Toronto

    ** NA= Not applicable / NR: Not reported / SMR: Standardised mortality ratio / SIR: Standardised incidence raio / RR=relative risk / OR=odds ratio

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