The carcinogenicity of metals in humans

Epidemiologic evidence on the relation between exposure to metals and cancer is reviewed. Human exposure to metals is common, with wide use in industry and long-term environmental persistence. Historically, the heaviest metal exposures occurred in the workplace or in environmental settings in close proximity to industrial sources. Among the general population, exposure to a number of metals is widespread but generally at substantially lower levels than have been found in industry. The carcinogenicity of arsenic, chromium, and nickel has been established. Occupational and environmental arsenic exposure is linked to increased lung cancer risk in humans, although experimental studies remain inconclusive. Experimental studies clearly demonstrate the malignant potential of hexavalent (VI) chromium compounds, with solubility being an important determining factor. Epidemiologic studies of workers in chromium chemical production and use link exposure to lung and nasal cancer. Experimental and epidemiologic data show that sparingly-soluble nickel compounds and possibly also the soluble compounds are carcinogens linked to lung and nasal cancer in humans. Some experimental and epidemiologic studies suggest that lead may be a human carcinogen, but the evidence is inconclusive. Although epidemiologic data are less extensive for beryllium and cadmium, the findings in humans of excess cancer risk are supported by the clear demonstration of carcinogenicity in experimental studies. Other metals, including antimony and cobalt, maybe human carcinogens, but the experimental and epidemiologic data are limited.     

Evaluation of the in vitro direct and indirect genotoxic effects of cobalt compounds using the alkaline comet assay. Influence of interdonor and interexperimental variability

The mechanisms of cobalt-induced pulmonary interstitial fibrosis and cancer are incompletely understood. DNA damage, either induced by genotoxic (direct or via oxygen radicals) or co-genotoxic (e.g. inhibition of DNA repair) processes may play an important role in the initiation of cancer. The alkaline comet assay provides a sensitive tool to investigate these two processes. Cobalt metal, a mixture of cobalt with tungsten carbide and cobalt chloride, were compared for their DNA-damaging capacity. Concentrations from 0 to 6.0 microg Co- equivalent/ml were tested. All three compounds were able to induce DNA damage in isolated human lymphocytes from three donors, in a dose- and time-dependent way. A relatively large interexperimental and interdonor variability in response was observed. This was ascribed to technical parameters and unidentified individual factors. This confirms the importance of repeating experiments using the same and different donors. The DNA-damaging potential of the cobalt-tungsten carbide mixture was higher than that of cobalt metal and cobalt chloride, which had comparable responses. No significant increase of DNA migration was observed when the DNA of cells treated with cobalt metal, cobalt- tungsten carbide or tungsten carbide were incubated with the oxidative lesion-specific enzyme formamidopyrimidine DNA glycosylase. This suggests that during the short treatment period no substantial oxidative damage to DNA was produced. Cobalt metal was able to inhibit the repair of methylmethanesulphonate-induced DNA damage. This was concluded from simultaneous exposure to cobalt and methyl methanesulphonate, post-incubation and post-treatment with 1.2 microg/ml cobalt of methyl methanesulphonate-treated cells.      

Tobacco and occupation as risk factors in bladder cancer: a case-control study in southern Belgium

A pilot case-control study on bladder cancer, with population-based controls matched for each of 74 cases, has been conducted in two industrial areas of Southern Belgium in order to analyze the influence of tobacco use and occupation. Observed bladder cancer risk for smokers is more than 5 times higher than that for non-smokers, and the risk for people having an a priori hazardous occupation is about 3.5 times higher than that of other subjects. A dose-response relationship was found for tobacco exposure and duration of employment. It seems that the risk is increased in a log-linear way by these variables. Population attributable risks show that in 20 cases of bladder cancer, 17 could be explained by the two factors combined. This study also reveals an increased risk for metal workers, truck and engine drivers, coal-miners, and rubber and coal-tar workers. The risk for metal workers is specially high in the case of turners, metal fitters, blacksmiths, stokers and workers exposed to hot metal.     

Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects

Heavy metal-tungsten alloys (HMTAs) are dense heavy metal composite materials used primarily in military applications. HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%) and either cobalt (2-4%) or iron (2-4%) particles. Like the heavy metal depleted uranium (DU), the use of HMTAs in military munitions could result in their internalization in humans. Limited data exist, however, regarding the long-term health effects of internalized HMTAs in humans. We used an immortalized, non-tumorigenic, human osteoblast-like cell line (HOS) to study the tumorigenic transforming potential of reconstituted mixtures of tungsten, nickel and cobalt (rWNiCo) and tungsten, nickel and iron (rWNiFe). We report the ability of rWNiCo and rWNiFe to transform immortalized HOS cells to the tumorigenic phenotype. These HMTA transformants are characterized by anchorage-independent growth, tumor formation in nude mice and high level expression of the K-ras oncogene. Cellular exposure to rWNiCo and rWNiFe resulted in 8.90 +/- 0.93- and 9.50 +/- 0.91-fold increases in transformation frequency, respectively, compared with the frequency in untreated cells. In comparison, an equivalent dose of crystalline NiS resulted in a 7.7 +/- 0.73-fold increase in transformation frequency. The inert metal tantalum oxide did not enhance HOS transformation frequency above untreated levels. The mechanism by which rWNiCo and rWNiFe induce cell transformation in vitro appears to involve, at least partially, direct damage to the genetic material, manifested as increased DNA breakage or chromosomal aberrations (i.e. micronuclei). This is the first report showing that HMTA mixtures of W, Ni and Co or Fe cause human cell transformation to the neoplastic phenotype. While additional studies are needed to determine if protracted HMTA exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized HMTAs exposure may be comparable with the risk from other biologically reactive and insoluble carcinogenic heavy metal compounds (e.g. nickel subsulfide and nickel oxide).     

Life-style, workplace, and stomach cancer by subsite in young men of Los Angeles County

A case-control study involving interviews with 137 incident male cases of stomach cancer under the age of 55 yr and an equal number of age- (within 5 yr), race-, and sex-matched neighborhood controls in Los Angeles County was conducted. Cases were more likely to be foreign born and had less education compared with controls. Any use of tobacco products conferred a 2-fold increase risk for stomach cancer; the effect was present in all subsites: the cardia; fundus/body; and antrum/pylorus. Weekly use of alcoholic beverages was also a risk factor, but the effect was not observed in the antrum/pylorus. In comparison with controls, cases had a significantly higher intake of beef (cardia only) and barbecued/smoked foods, had a lower intake of fresh fruits/vegetables, and were more likely to prefer white than whole grain bread. Occupational exposure to metal dust was associated with a 70% increased risk of stomach cancer, with an increase in risk as the duration of exposure increased. This association was most pronounced for tumors in the antrum and pylorus. Subjects with a history of stomach or duodenal ulcer showed a 2-fold increased risk of stomach cancer. The effects of smoking, alcohol, intake of white bread, history of ulcer, and exposure to metal dust remained statistically significant when these variables were examined simultaneously in multivariate analyses and when the multivariate analyses were confined to directly interviewed subjects.     

美国吸烟者与非吸烟者肺癌流行病学概况

人们已清楚知道，吸烟是肺癌的主要危险因素，也知道吸烟和职业暴露以外的因素在某些肺癌特别是腺癌中起作用。本文以医院病例为基础进行大样本的病冽对照研究来分析肺癌与吸烟因素（吸烟量，过滤咀烟，黑白人种的吸烟习惯）及非吸烟因素（ＥＴＳ暴露，原发性肿瘤和治疗，生殖和内分泌因素，躯体指数）的联系。虽然吸烟与所有主要细胞类型的肺癌都有剂量－效应关系，但与腺癌的联系强度较弱，提示吸烟以外的因素对腺癌的重要性。在白人和黑人中，无论男、女，肺癌的ＯＲ值均随香烟焦油摄入量的增加而增加，并随戒烟年限的延长而减少。是否吸含薄荷香烟，对肺癌的危险性影响不大。未见到ＥＴＳ与肺癌的联系，即使丈夫吸烟也未能使不吸烟妻子患肺癌的危险性增加。生殖系统原发性肿瘤和放射治疗，可使不吸烟女性患肺癌的危险性增加４倍。曾观察到身体瘦弱与现在吸烟、以前吸烟和从不吸烟的女性肺癌之间的联系。以上结果在本文中分别加以讨论。总的来说，人群中肺癌患病率的不同，可能由于：（１）香烟烟雾中的致癌物不同；（２）香烟烟雾的作用因素不同，包括受到机体敏感性及对致癌物的代谢的影响；（３）暴露于吸烟以外的其他各种危险因素     

Toenail trace element status and risk of Barrett's oesophagus and oesophageal adenocarcinoma: results from the FINBAR study

Trace elements have been cited as both inhibitory and causative agents of cancer but importantly exposure to them is potentially modifiable. Our study aimed to examine toenail trace element status and risk of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Toenail clippings from each hallux were obtained from 638 participants of the FINBAR (Factors Influencing the Barrett's Adenocarcinoma Relationship) study comprising 221 healthy controls, 98 reflux oesophagitis, 182 BO and 137 OAC cases. The concentrations of eight toenail trace elements were determined using instrumental neutron activation analysis. Using multivariable adjusted logistic regression analysis, odds ratios (OR) and 95% confidence intervals (CIs) were calculated within tertiles of trace element concentrations. A twofold increased risk of BO was observed, but not OAC, among individuals in the highest tertile of toenail zinc status OR 2.21 (95% CI, 1.11-4.40). A higher toenail selenium status was not associated with risk of OAC OR 0.94 (95% CI, 0.44-2.04) or BO OR 0.89 (95% CI, 0.37-2.12). A borderline significant increased risk of BO was detected with a higher toenail cobalt concentration, OR 1.97 (95% CI, 1.01-3.85). No association was found between toenail levels of chromium, cerium, mercury and OAC or BO risk. This is the first case-control study to investigate a variety of trace elements in relation to OAC and BO risk. Despite antioxidant and proapoptotic properties, no associations were found with selenium. Higher concentrations of toenail zinc and cobalt were associated with an increased BO risk, but not OAC. These findings need confirmation in prospective analysis.     

Air pollution and lung cancer mortality in the vicinity of a nonferrous metal smelter in Sweden

To evaluate the importance of exposure to ambient air pollution for lung cancer risk, we conducted a case-control study in the vicinity of a nonferrous metal smelter. The smelter started operations in 1930 and had very high emissions during the early decades, particularly of arsenic and SO(2). Among subjects deceased 1961-1990 in the municipality where the smelter is located and who had not worked at the smelter, 209 male and 107 female lung cancer cases were identified and matched by sex and year of birth to 518 and 209 controls, respectively. Information on smoking habits, occupations and residences was collected by questionnaire to next-of-kin and from registry data. Living close to the smelter was associated with a relative risk (RR) for lung cancer of 1.38 [95% confidence interval (CI) 0.89-2.14] among men, adjusted for smoking and occupational exposures. No clear difference in risk was detected for men deceased 1961-1979 compared to men deceased 1980-1990 (RR point estimates 1.42 and 1.29, respectively). There appeared to be an increased risk especially for men exposed in the beginning of the operations (RR = 1.51, 95% CI 0.90-2.54), in particular combined with exposure duration shorter than 20 years (RR = 2.52, 95% CI 0.89-7.11). For women, however, no overall increased risk for lung cancer was observed. Although not significant, our findings thus indicated an increased risk of lung cancer among men living close to the nonferrous smelter. This increase appeared to concern primarily men exposed during the early years of operations, when emissions were very high.     

Meta-analysis of case-referent studies of specific environmental or occupational pollutants on lung cancer

BACKGROUND: Meta-analysis is a statistical tool for combining and integrating the results of independent studies of a given scientific issue. The present investigation was initiated to investigate case-referent studies of lung cancer risk from specific environmental and occupational pollutants, using detailed individual exposure data. MATERIALS AND METHODS: To examine the risk of lung cancer associated with environmental and occupational pollutants, a meta-analysis of published case-control studies was undertaken using a random effects model. For this study, the papers were selected for review from electronic search of PubMed, Medline and Google Scholar during 1990-2006. The principal outcome measure was the odds ratio for the risk of lung cancer. Twelve study reports detailing the relationship between the lung cancer and the type of exposure were identified. RESULTS: The odds ratio of asbestos, cooking fuel, cooking fumes, motor and diesel exhaust related to lung cancer were 1.67, 1.99, 2.52 and 1.42 (P < 0.001), respectively. The odds ratio of metal fumes related to lung cancer was 1.28 (0.001 P < 0.01). The combined odds ratio for the environmental and occupational exposure related to lung cancer was 1.67 (P < 0.001). CONCLUSIONS: The meta-analysis of the present study shows the magnitude association between asbestos, cooking fumes, cooking fuels, motor and diesel exhaust, with lung cancer risk. Lung cancer risk may be reduced by controlling exposure levels.     

Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype

The risk of lung cancer in smokers was examined based on the debrisoquine metabolic phenotype and on exposure to occupational lung carcinogens, specifically asbestos and polycyclic aromatic hydrocarbons. Extensive metabolizers of debrisoquine are at a 4-fold increased risk for lung cancer compared to poor metabolizers, after adjustment for age, sex, and smoking (pack-years), when only occupationally unexposed subjects are considered. Increased risk related to the debrisoquine metabolic phenotype was greatest for squamous and small cell histologies, and least for the adenocarcinoma subtype. Men with a history of exposure to occupational carcinogens had significantly increased risk of lung cancer (relative risk = 2.8), after adjustment for age and smoking. Considering the combined effect of the high risk extensive metabolizers debrisoquine metabolic phenotype and likely occupational exposure to asbestos, the relative excess risk for lung cancer was 18-fold. This finding is consistent with a synergism in risk between the ability to extensively metabolize debrisoquine and occupational exposure to lung carcinogens in male smokers. Debrisoquine phenotyping has potential for identifying carcinogen-exposed workers at high risk of lung cancer.     

Case-control study of bladder cancer in New Jersey. I. Occupational exposures in white males

The occupational bladder cancer risk for New Jersey white males was estimated with the use of both industry-job title-based and exposure-based analyses of data from 658 incident cases and 1,258 general population controls. The overall bladder cancer risk attributable to occupational exposures was estimated as 20-22%. A wide variety of employment categories and exposures contributed to this risk. Odds ratios were significantly high for employment as garage and gas station workers and food counter workers and/or cooks and for exposure to leather, rubber, paint, printing ink, and other organic compounds. Odds ratios for textile mill workers, chemical workers, and metal workers for the a priori high-risk employment category and odds ratios for those exposed to dyes, chlorinated compounds, and rubber showed significant differences between younger and older subjects. Bladder cancer risk associated with occupational exposures was not limited to persons with initial exposures before 25 years of age. However, there was significantly decreasing risk for bladder cancer with increasing age at first exposure for chemical workers and metal workers and for the a priori high-risk materials and metals. Drivers and/or deliverymen and miscellaneous laborers had significantly increasing bladder cancer risk with increasing duration of employment.     

Occupation and bladder cancer among men in Western Europe

OBJECTIVES: We examined which occupations and industries are currently at high risk for bladder cancer in men. METHODS: We combined data from 11 case-control studies conducted between 1976-1996 in six European countries. The study comprised 3346 incident cases and 6840 controls, aged 30-79 years. Lifetime occupational and smoking histories were examined using common coding. RESULTS: Odds ratios for eight a priori defined high-risk occupations were low, and with the exception of metal workers and machinists (OR = 1.16, 95% CI = 1.02-1.32), were not statistically significant. Higher risks were observed for specific categories of painters, metal, textile and electrical workers, for miners, transport operators, excavating-machine operators, and also for non-industrial workers such as concierges and janitors. Industries entailing a high risk included salt mining, manufacture of carpets, paints, plastics and industrial chemicals. An increased risk was found for exposure to PAHs (OR for highest exposure tertile = 1.23, 95% CI = 1.07-1.4). The risk attributable to occupation ranged from 4.2 to 7.4%, with an estimated 4.3% for exposure to PAHs. CONCLUSIONS: Metal workers, machinists, transport equipment operators and miners are among the major occupations contributing to occupational bladder cancer in men in Western Europe. In this population one in 10 to one in 20 cancers of the bladder can be attributed to occupation.     

Passive smoking and lung cancer in Chandigarh, India.

The aim of this study is to assess the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers, a case-control study among lifetime non-smokers was conducted in Chandigarh, India. Cases consisted of 58 non-smoking histologically confirmed lung cancer patients; two controls for each case were selected, one among other patients admitted to the wards and one among the visitors to hospital patients. Subjects were asked about ETS exposure from different tobacco products in childhood and in adulthood at home, at the work place and in vehicles. Multivariate logistic regression analysis was used to assess the effects of the ETS exposure variables on lung cancer. Exposure to ETS during childhood was strongly associated with lung cancer (odds ratio (OR) = 3.9; 95% confidence interval (CI) = 1.9-8.2), the effect mostly arising from exposure to cigarettes smoke. The excess risk was observed with either a smoking father or mother. An increasing risk was found with increasing number of smokers and duration of exposure. Restricting the analysis to women produced higher estimates of the risk. No increased risk was found with exposure to a smoking spouse, except for those exposed only to cigarette smoke (OR = 5.1; 95% CI = 1.5-17). A weak association was seen between lung cancer and ETS exposure at the workplace, which increased with the number of years of exposure. Exposure in vehicles also was detected as a risk factor for lung cancer in non-smokers. This study suggests that ETS exposure may be a strong risk factor for lung cancer also in India, a country with low prevalence of smoking and, therefore, low rates of lung cancer. Other studies need to be conducted in similar settings to confirm the role played by ETS exposure early in life in the causation of lung cancer.     

Bladder cancer risk in relation to occupations held in a nationwide case-control study in Iran

Globally, bladder cancer has been identified as one of the most frequent occupational cancers, but our understanding of occupational bladder cancer risk in Iran is less advanced. This study aimed to assess the risk of bladder cancer in relation to occupation in Iran. We used the IROPICAN case-control study data including 717 incident cases and 3477 controls. We assessed the risk of bladder cancer in relation to ever working in major groups of the International Standard Classification of Occupations (ISCO-68) while controlling for cigarette smoking, opium consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). In men, decreased ORs for bladder cancer were observed in administrative and managerial workers (OR 0.4; CI: 0.2, 0.9), and clerks (OR 0.6; CI: 0.4, 0.9). Elevated ORs were observed in metal processors (OR 5.4; CI: 1.3, 23.4), and workers in occupations with likely exposure to aromatic amines (OR 2.2; CI: 1.2, 4.0). There was no evidence of interactions between working in aromatic amines-exposed occupations and tobacco smoking or opium use. Elevated risk of bladder cancer in men in metal processors and workers likely exposed to aromatic amines aligns with associations observed outside Iran. Other previously confirmed associations between high-risk occupations and bladder cancer were not observed, possibly due to small numbers or lack of details on exposure. Future epidemiological studies in Iran would benefit from the development of exposure assessment tools such as job exposure matrices, generally applicable for retrospective exposure assessment in epidemiological studies.     

Historical Long-term Exposure to Pentachlorophenol CausingRisk of Cancer - A Community Study

Background: Pervious studies suggested occupational workers exposure to pentachlorophenol (PCP) mightcontribute to increased risk of cancer. However, few studies have focused on associations between PCP and cancerrisk at the community level. Objective: The present study was to explore the cancer risk for the communitypopulation living long-term in a PCP contaminated area. Methods: All the cancer cases diagnosed in 2009-2011 in Tongling City were collected. The cancer patients’ residencies were geo-referenced in each district. Thehistorical PCP usage for each district of Tongling was calculated as the PCP pollution index, which was furtherused to divide into PCP exposure categories. Standardized rate ratios (SRRs) of cancer incidence were applied todetect the cancer risk as exposure grade elevated. Correlation analysis was performed to analyze the relationshipbetween PCP pollution and cancer incidence. Results: A total of 5,288 cancer cases (3,451 male and 1,837 female)were identified. PCP usage was correlated with the incidence of leukemia (r=0.88, P=0.002) for males, and withcancer of the esophagus for males (r=0.83, P=0.008) and females (r=0.71, P=0.020). Compared with the lowexposure category, significant SRRs for total cancer sites was obtained for high PCP exposure category (SRR=1.61,95%CI=1.59-1.62). Most SRR values of the cancer sites were significantly increased as exposure grade elevatedand exposure time extended. Conclusion: The present study found that community residents living in the PCPcontaminated area had increased risk of cancers. Leukemias, lymphomas and nasopharyngeal and esophagealcancers are most possibly associated with PCP exposure.     

Life course sun exposure and risk of prostate cancer: Population‐based nested case‐control study and meta‐analysis

There is currently no means of primary prevention for prostate cancer. Increased exposure to ultraviolet‐radiation may be protective, but the literature is inconclusive. We investigated associations of life course exposure to sunlight with prostate cancer. The study design was a UK‐wide nested case‐control study, based on 1,020 prostate specific antigen‐detected cases and 5,044 matched population controls and a systematic review with meta‐analysis. Men with olive/brown skin (OR = 1.47; 95% CI: 1.00 to 2.17), men who burnt rarely/never (OR = 1.11; 0.95 to 1.29) and men with the lowest levels of intense sun exposure in the 2 years prior to diagnosis (OR = 1.24; 1.03 to 1.50) had an increased prostate cancer risk. However, amongst men with prostate cancer, spending less time outside was associated with a reduced risk of advanced cancer (OR = 0.49; 0.27 to 0.89) and high Gleason grade (OR = 0.62; 0.43 to 0.91), and men who burnt rarely/never had a reduced risk of advanced cancer (OR = 0.71; 0.47 to 1.08). The meta‐analysis provided weak evidence that men with the lowest (versus highest) sunlight exposure had an increased prostate cancer risk (4 studies, random‐effects pooled relative risk = 1.13; 0.98 to 1.29) and higher advanced or fatal prostate cancer risk (6 studies, random‐effects pooled relative risk = 1.14; 0.98 to 1.33). Our data and meta‐analyses provide limited support for the hypothesis that increased exposure to sunlight may reduce prostate cancer risk. The findings warrant further investigation because of their implications for vitamin D chemoprevention trials. © 2009 UICC     

Diagnostic X-ray and ultrasound exposure and risk of childhood cancer.

In a population-based case-control study of 642 childhood cancer cases and the same number of matched controls in Shanghai, China, we evaluated the relationship between diagnostic X-ray (preconception, pre- and post-natal) and antenatal ultrasound exposure and the subsequent risk of developing three major types of childhood cancer (acute leukaemia, lymphoma and brain tumours) and all childhood neoplasms combined. Consistent with previous studies, prenatal X-ray exposure was found to be associated with an 80% increased risk of childhood cancers, although the estimation was based on 4% and 2% exposed cases and controls and was only marginally statistically significant (P = 0.08). Post-natal X-ray exposure was also linked with a small elevation in the risk of all cancers and the major categories of malignancies in children. Little evidence, however, was found to relate parental preconception X-ray exposure with the subsequent cancer risk in offspring, regardless of the exposure window and the anatomical site of X-ray exposures. This study adds further to the growing literature indicating that antenatal ultrasound exposure is probably not associated with an increased risk of childhood cancer.     

Urinary lead exposure and breast cancer risk in a population-based case-control study

BACKGROUND: Lead is a toxic nonessential metal with widespread exposure starting in utero. Lead has been reclassified in 2004 by the International Agency for Research on Cancer Working Group from a "possible" to a "probable" human carcinogen. Lead may be a facilitative or permissive carcinogen, which means that lead may permit or augment the genotoxic effects of other exposures. METHODS: This population-based study in Wisconsin gathered survey data and home-collected urine specimens from 246 women, ages 20 to 69 years, with incident invasive breast cancer identified from the Wisconsin state registry and 254 age-matched control subjects from population lists from September 2004 to February 2005. We measured urinary lead concentrations by inductively coupled plasma mass spectrometry, adjusted the values by specific gravity, and conducted interviews by telephone to obtain information on known and suspected breast cancer risk factors. RESULTS: Women in the highest quartile of specific gravity-adjusted lead level (>/=1.10 mug/L) had twice the breast cancer risk of those in the lowest quartile (<0.42 mug/L; odds ratio, 1.99; 95% confidence interval, 1.1-3.6) after adjustment for established risk factors. Excluding women who were currently taking nonsteroidal aromatase inhibitors (n = 52), we did not observe any increased breast cancer risk after adjustment for established risk factors. CONCLUSION: Our population-based case-control study suggests that lead exposure, as determined by specific gravity-adjusted urinary lead concentrations, is not associated with a significant increased risk for breast cancer.     

Organic solvents and cancer

Epidemiologic evidence on the relationship between organic solvents and cancer is reviewed. In the 1980s, more than a million persons were potentially exposed to some specific solvents in the United States; in Canada, 40 percent of male cancer patients in Montreal had experienced exposure to solvents; in the Finnish population, one percent was regularly exposed. There is evidence for increased risks of cancer following exposure to: trichloroethylene (for the liver and biliary tract and for non-Hodgkin's lymphomas); tetrachloroethylene (for the esophagus and cervix - although confounding by smoking, alcohol, and sexual habits cannot be excluded - and non-Hodgkin's lymphoma); and carbon tetrachloride (lymphohematopoietic malignancies). An excess risk of liver and biliary tract cancers was suggested in the cohort with the high exposure to methylene chloride, but not found in the other cohorts where an excess risk of pancreatic cancer was suggested. 1,1,1-trichloroethane has been used widely, but only a few studies have been done suggesting a risk of multiple myeloma. A causal association between exposure to benzene and an increased risk of leukemia is well-established, as well as a suggested risk of lung and nasopharynx cancer in a Chinese cohort. Increased risks of various gastrointestinal cancers have been suggested following exposure to toluene. Two informative studies indicated an increased risk of lung cancer, not supported by other studies. Increased risks of lymphohematopoietic malignancies have been reported in some studies of persons exposed to toluene or xylene, but not in the two most informative studies on toluene. Occupation as a painter has consistently been associated with a 40 percent increased risk of lung cancer. (With the mixed exposures, however, it is not possible to identify the specific causative agent[s].) A large number of studies of workers exposed to styrene have evidenced no consistent excess risk of all lymphohematopoietic malignancies, although the most sensitive study suggested an excess risk of leukemia among workers with a high exposure.