Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries.

OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Occupational exposure to lead compounds and risk of cancer among men: a population-based case-control study.

The International Agency for Research on Cancer recently classified inorganic lead as a probable carcinogen, while organic lead remained unclassifiable. Uncertainty persists because of limited epidemiologic evidence. The authors addressed the relation between occupational exposure to lead and the risk of 11 types of cancer among men in a case-control study conducted in Montreal, Quebec, Canada, in the 1980s. Incident cases (n = 3,730) and general population controls (n = 533) were interviewed to elicit information on job history and potential confounders. Expert chemists translated each job into a list of substances to which the subject had potentially been exposed. Exposure to lead was classified into three categories: organic lead (3% of subjects ever exposed), inorganic lead (17%), and lead in gasoline emissions (39%). Odds ratios and 95% confidence intervals were estimated by logistic regression using two control groups: general population controls and cancer controls. Stomach cancer was associated with organic lead when the authors used population controls (odds ratio (OR) = 3.0, 95% confidence interval (CI): 1.2, 7.3) and cancer controls (OR = 2.0, 95% CI: 1.1, 3.8) and with substantial exposure to lead in gasoline emissions when they used cancer controls (OR = 2.9, 95% CI: 1.4, 5.9). There was no association with inorganic lead and little evidence for associations with other cancer types.

Exposure to titanium dioxide and risk of lung cancer in a population-based study from Montreal.

OBJECTIVES: This study assessed the lung cancer risk from exposure to titanium dioxide, an important pigment with limited evidence of carcinogenicity in experimental animals but sparse data for humans. METHODS: The risk of lung cancer among residents in Montreal, Canada, was analyzed, including 857 histologically confirmed cases of lung cancer diagnosed during 1979-1985 among men aged 35-70 years and a group of referents comprising 533 randomly selected, healthy residents and 533 persons with cancer in organs other than the lung. Exposure to titanium dioxide and other titanium compounds was assessed by a team of industrial hygienists on the basis of a detailed occupational questionnaire. RESULTS: Thirty-three cases and 43 referents were classified as exposed to titanium dioxide. The odds ratio was 0.9 [95% confidence interval (95% CI) 0.5-1.5]. No trend was apparent according to the estimated frequency, level, or duration of exposure. The odds ratio was 1.0 (95% CI 0.3-2.7) for medium or high exposure for at least 5 years. Few subjects were classified as exposed to titanium dioxide fumes or to other titanium compounds, but the risk of lung cancer was nonsignificantly increased for exposure to these agents. CONCLUSIONS: Although misclassification of exposure and low exposure prevalence might have resulted in false negative results, this study does not suggest that occupational exposure to titanium dioxide increases the risk of lung cancer.

A case-control study of the relationship between the risk of colon cancer in men and exposures to occupational agents.

BACKGROUND: We conducted a population-based case-control study in Montreal, Canada, to explore associations between hundreds of occupational circumstances and several cancer sites, including colon. METHODS: We interviewed 497 male patients with a pathologically confirmed diagnosis of colon cancer, 1514 controls with cancers at other sites, and 533 population-based controls. Detailed job histories and relevant potential confounding variables were obtained, and the job histories were translated by a team of chemists and industrial hygienists into a history of occupational exposures. RESULTS: We found that there was reasonable evidence of associations for men employed in nine industry groups (adjusted odds ranging from 1.1 to 1.6 per a 10-year increase in duration of employment), and in 12 job groups (OR varying from 1.1 to 1.7). In addition, we found evidence of increased risks by increasing level of exposures to 21 occupational agents, including polystyrene (OR for "substantial" exposure (OR(subst)) = 10.7), polyurethanes (OR(subst) = 8.4), coke dust (OR(subst) = 5.6), mineral oils (OR(subst) = 3.3), polyacrylates (OR(subst) = 2.8), cellulose nitrate (OR(subst) = 2.6), alkyds (OR(subst) = 2.5), inorganic insulation dust (OR(subst) = 2.3), plastic dusts (OR(subst) = 2.3), asbestos (OR(subst) = 2.1), mineral wool fibers (OR(subst) = 2.1), glass fibers (OR(subst) = 2.0), iron oxides (OR(subst) = 1.9), aliphatic ketones (OR(subst) = 1.9), benzene (OR(subst) = 1.9), xylene (OR(subst) = 1.9), inorganic acid solutions (OR(subst) = 1.8), waxes, polishes (OR(subst) = 1.8), mononuclear aromatic hydrocarbons (OR(subst) = 1.6), toluene (OR(subst) = 1.6), and diesel engine emissions (OR(subst) = 1.5). Not all of these effects are independent because some exposures occurred contemporaneously with others or because they referred to a group of substances. CONCLUSIONS: We have uncovered a number of occupational associations with colon cancer. For most of these agents, there are no published data to support or refute our observations. As there are few accepted risk factors for colon cancer, we suggest that new occupational and toxicologic studies be undertaken focusing on the more prevalent substances reported herein.

Cancer mortality among males in relation to exposures assessed through a job-exposure matrix.

To identify potential associations between workplace exposures and cancer mortality risks, job titles collected from 1965 to 1971 for 58,678 men (a subset of a large representative sample of the Canadian workforce) were transformed into probable chemical exposures using a job-exposure matrix developed in Montreal. Mortality follow-up was determined through computerized record linkage with the National Mortality Database in Canada for 1965-1991. Cancer mortality risk was evaluated at two levels of exposure, any and substantial, using Poisson regression controlling for age, calendar period, and social class. Among the 58,678 men, 3,160 died of cancer. Using a liberal reporting criterion, relative risk (RR) >1.0, five or more exposed cancer deaths, p < or = 0.100, several potential associations were identified, including: lung cancer and any exposure to abrasives dust (RR = 2.84), prostate cancer and any exposure to calcium carbonate (RR = 2.46), and prostate cancer and substantial exposure to metallic dust (RR = 2.13).

Evaluation of the potential promoting effect of 60 Hz magnetic fields on N-ethyl-N-nitrosourea induced neurogenic tumors in female F344 rats.

The present study investigated the possible effect of 60 Hz magnetic fields (MFs) as promoters of neurogenic tumors initiated transplacentally by a chemical carcinogen, N-ethyl-N-nitrosourea (ENU). In a preliminary study, 5 mg of ENU was shown to induce 30 to 40% neurogenic tumors in F344 rats offspring after 420 days of observation. In the present study, 400 female rats were divided into eight different groups (50 animals/group) and exposed in utero (on day 18 of gestation) to a single intravenous dose of either Saline (Group I), or ENU, 5 mg/kg (Group II to VIII). Dams in group II were given no further treatment while dams in Groups III to VII were exposed to 5 different intensities of MFs forty eight hours later. Animals in group III were sham exposed (<0.02 microT) while groups IV to VII were exposed to 2, 20, 200, and 2000 microT, respectively. Dams in Group VIII were injected intraperitoneally with 12-O-tetradecanoylphrobol-13-acetate (TPA; 10 micrograms/kg) from day 19 until delivery, and then their female offspring continued to be injected every 15 days, starting at day 14 after birth until sacrifice (positive controls). Accordingly, this study included three different types of controls: Internal controls (Groups II and III) and positive control (Group VIII). Body weight, mortality and clinical observations were evaluated in all groups of animals during in-life exposure. Necropsy was performed on all exposed and control animals that died, were found moribund or sacrificed at termination of the study. Histopathological evaluation was done for all brains, spinal cords, cranial nerves, major organs (lungs, liver, spleen, kidneys, pituitary, thyroid and adrenals) and all gross lesions observed during necropsy. All clinical observations and pathological evaluations were conducted under "blinded" conditions. The findings from this ENU/MFs promotion study clearly demonstrate that, under our defined experimental conditions, exposure to 60 Hz linear (single axis) sinusoidal, continuous wave MFs had no effect on the survival of female F344 rats or on the number of animals bearing neurogenic tumors. These results suggest that MFs have no promoting effect on neurogenic tumors in the female F344 rats exposed transplacentally to ENU.

Evaluation of the potential carcinogenicity of 60 Hz linear sinusoidal continuous-wave magnetic fields in Fischer F344 rats.

Electric and magnetic fields (EMFs) associated with the production, transmission, and use of electricity are ubiquitous in industrialized societies. These fields are predominantly of low frequency (50/60 Hz) and are generally of low intensity. Review of the epidemiological evidence shows that the association between exposure to EMFs and cancer is weak and inconsistent, and generally fails to show a dose-response relationship. Moreover, in view of the methodological problems of these epidemiological studies, animal and laboratory studies are urgently needed to determine whether EMFs could be initiators and/or promoters of cancers. The objective of the present study was to determine whether chronic exposure to 60 Hz linear (single axis) sinusoidal, continuous-wave magnetic fields (MFs) of different intensities might increase the risk of leukemia and solid tumor development in rodents born and raised under these fields. Five groups of 50 female F344 rats were exposed for 20 h/day to 60 Hz MFs at intensities of <0.02 (sham controls), 2, 20, 200, and 2000 microT. Full body exposure to the different fields was administered for 104 wk starting from the prenatal period (2 days before birth) and continuing during lactation and weaning until late adult life. Body weight, survival, and clinical observations were evaluated in all groups of animals during in-life exposure. Necropsy was performed on all exposed and control animals that died, were found moribund, or were killed at termination of the study. To preserve and demonstrate the absence of any experimental bias, all clinical observations and pathological evaluations were conducted under "blinded" conditions. Fifty organs and tissues were evaluated in each animal, with special attention to the incidence of mononuclear cell leukemia, brain tumors, and mammary tumors. The findings from this chronic carcinogenicity study demonstrate that, under our defined experimental conditions, exposure to 60 Hz linear (single axis) sinusoidal, continuous wave MFs did not affect animal survival, solid tumor, or mononuclear cell leukemia development in female F344 rats. No statistically significant, consistent, positive dose-related trends with the number of tumor-bearing animals per study group could be attributed to MF exposure.

Reliability of an expert rating procedure for retrospective assessment of occupational exposures in community-based case-control studies.

The most daunting problem in community-based studies of occupational cancer is retrospective exposure assessment. To avoid the error involved in using job title as the exposure variable or self-report of exposure, our team developed an approach based on expert judgment applied to job descriptions obtained by interviewers. A population-based case-control study of cancer and occupation was carried out in Montreal between 1979 and 1986, and over 4,000 job histories were assessed by our team of experts. The job histories of these subjects were evaluated, by consensus, by a team of chemist/hygienists for evidence of exposure to a list of 294 workplace chemicals. In order to evaluate the reliability of this exposure assessment procedure, four years after the rating was completed, we selected 50 job histories at random and had two members of the expert team carry out the same type of coding, blind to the original ratings for these jobs. For 25 job histories, comprising 94 distinct jobs, the pair worked as a consensus panel; for the other 25, comprising 92 distinct jobs, they worked independently. Statistical comparisons were made between the new ratings and the old. Among those rated by consensus, the marginal distribution of exposure prevalence was almost identical between old and new. The weighted kappa for agreement was 0.80. Among items for which both ratings agreed that there had been exposure, there was good agreement on the frequency, concentration, and route of contact. When the two raters worked independently, the levels of agreement between them and between each of them and the original rating was good (kappas around 0.70), though not as high as when they worked together. It is concluded that high levels of reliability are attainable for retrospective exposure assessment by experts.

Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) demonstrate carcinogenic activity in animal models. Although some epidemiologic studies have implicated PAHs as risk factors for human cancer, the evidence reported to date has not been consistent. The purpose of this report is to describe the associations between occupational exposure to PAHs in the workplace and each of 14 types of cancer. A population-based, case-control study was carried out in Montreal to investigate associations between a large variety of environmental and occupational exposures on the one hand, and several types of cancer on the other. A detailed job history was obtained from each subject along with information on a number of potential confounders. Each job history was reviewed by a team of experts, who used this information to construct a corresponding history of occupational exposures. Among the PAH exposures considered were benzo(a)pyrene (B(a)P) and five categories of PAHs defined on the basis of the source material, namely, wood, petroleum, coal, other sources, and any source. Altogether, 3,730 cancer patients and 533 population controls were interviewed and their job exposure histories coded. For each of 14 types of cancer analyzed, three control groups were available: other cancer patients, population controls, and the pooled set of cancer and population controls. The associations between 14 cancer types and 6 PAH exposures were analyzed using logistic regression methods. For most types of cancer evaluated, there was no evidence of excess risk due to PAHs at the levels encountered in the occupations in which PAH exposure has been prevalent in the Montreal area. For a few cancer sites--the esophagus, the pancreas, and the prostate gland--there were suggestions of excess risk; these observations are noteworthy hypotheses for further investigation. For lung cancer, there appeared to be an increased risk due to PAHs among nonsmokers and light smokers, but not among heavy smokers.

Occupational risk factors for bladder cancer: results from a case-control study in Montreal, Quebec, Canada.

A population-based case-control study of the associations between various cancers and occupational exposures was carried out in Montreal, Quebec, Canada. Between 1979 and 1986, 484 persons with pathologically confirmed cases of bladder cancer and 1,879 controls with cancers at other sites were interviewed, as was a series of 533 population controls. The job histories of these subjects were evaluated by a team of chemist/hygienists for evidence of exposure to a list of 294 workplace chemicals, and information on relevant non-occupational confounders was obtained. On the basis of results of preliminary analyses and literature review, 19 occupations, 11 industries, and 23 substances were selected for in-depth multivariate analysis. Logistic regression analyses were carried out to estimate the odds ratio between each of these occupational circumstances and bladder cancer. There was weak evidence that the following substances may be risk factors for bladder cancer: natural gas combustion products, aromatic amines, cadmium compounds, photographic products, acrylic fibers, polyethylene, titanium dioxide, and chlorine. Among the substances evaluated which showed no evidence of an association were benzo(a)pyrene, leather dust, and formaldehyde. Several occupations and industries were associated with bladder cancer, including motor vehicle drivers and textile dyers.

Cancer risks due to occupational exposure to formaldehyde: results of a multi-site case-control study in Montreal.

A case-control study was undertaken in Montreal to investigate the possible associations between occupational exposures and cancers of the following sites: oesophagus, stomach, colo-rectum, liver, pancreas, lung, prostate, bladder, kidney, melanoma and lymphoid tissue. In total, 3,726 cancer patients and 533 population controls were interviewed to obtain detailed lifetime job histories and information on potential confounders. Each job history was translated into a history of occupational exposures. Because of current concerns about formaldehyde carcinogenicity, we carried out a special analysis of the association between exposure to formaldehyde and each type of cancer covered by this study. Separate statistical analyses were carried out for each type of cancer using population controls as well as a control series drawn from among the other cancer sites in the study. Although nearly a quarter of all subjects had undergone occupational exposure to formaldehyde, the levels of exposure were in general quite low. There was no persuasive evidence of an increased risk of any type of cancer among men exposed to these levels of formaldehyde. However, the possibility of a small increase in risk could not be ruled out.

Cancer risks associated with 10 inorganic dusts: results from a case-control study in Montreal.

A multicancer site, multifactor case-control study was undertaken to generate hypotheses about possible occupational carcinogens. Probing interviews were carried out with eligible cases, comprising all incident cases of 20 types of cancer who were male, aged 35-70 years, and a resident in Montreal. The interview was designed to obtain detailed lifetime job histories and information on potential confounders. Each job history was reviewed by a team of chemists and industrial hygienists who translated it into a history of occupational exposures. These occupational exposures were then analyzed as potential risk factors in relation to the sites of cancer included; 3,726 cases were interviewed. For each site of cancer analyzed, controls were selected from among the other sites in the study. This report concerns the associations between the 12 main types of cancer in our series and 10 inorganic dusts that are found mainly in construction and metal industries. All site-exposure combinations were investigated. After intensive control for confounding, nonadenocarcinoma (NAC) of the lung was associated with long duration-high level exposure to silica (odds ratio [OR] = 1.4), excavation dust (OR = 1.9), concrete dust (OR = 2.5), abrasives dust (OR = 1.4), and alumina (OR = 1.5). It was difficult to disentangle the relative effects of those substances, and confounding among them was a distinct possibility. Although residual confounding by some uncontrolled factors may explain the elevated ORs, the results were compatible with the hypothesis of a nonspecific relation between NAC of the lung and respirable inorganic dusts as a class. Other associations that remained suggestive after in-depth analysis were silica and stomach cancer (OR = 1.2) and concrete dust and lymphoma (OR = 2.9).

Associations between several sites of cancer and ten types of exhaust and combustion products. Results from a case-referent study in Montreal.

A population-based case-referent study provided information on the associations between several types of cancer and 10 types of exhaust and combustion products. All site-exposure combinations were investigated. An increased lung cancer risk, in particular squamous-cell cancers, due to exposure to gasoline and diesel exhausts was found. Among the associations that have not been subject to previous attention, the most promising leads for further investigation are the possible relations between gasoline and diesel exhaust and colorectal cancers, gasoline exhaust and kidney cancer, coal combustion products and pancreatic cancer (and possibly nonadenocarcinoma lung cancer), combustion products of heating oil and prostatic cancer, and natural-gas combustion products and bladder cancer.

Associations between several sites of cancer and twelve petroleum-derived liquids. Results from a case-referent study in Montreal.

A population-based case-referent study provided information on the associations between several types of cancer and 12 petroleum-derived liquids. All site-exposure combinations were investigated. The most interesting results concerned the following combinations: leaded gasoline-stomach cancer, aviation gasoline-kidney cancer (and the possible implications of this association for a similar effect of unleaded automotive gasoline), mineral spirits-squamous-cell cancer of the lung, diesel fuel-nonadenocarcinoma lung cancer, lubricating oils-squamous-cell lung cancer, cutting fluids-bladder cancer, other mineral oils-bladder cancer, mineral spirits-prostate cancer, diesel fuel-prostate cancer, and lubricating oils-prostate cancer.