The reproductive toxicity and carcinogenicity of lead: a critical review.
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Animals↗
Biomedical subjects
P Boffetta
Publications and source records attributed to P Boffetta.
Lead and cancer in humans: where are we now?
BACKGROUND: Lead is only weakly mutagenic, but in vitro it inhibits DNA repair and acts synergistically with other mutagens. Lead acetate administered orally, cutaneously, or intraperitoneally causes kidney cancer, brain cancer (gliomas), and lung cancer in rodents, and acts synergistically with other carcinogens. Most cytogenetic studies of exposed workers have shown increases in chromosome aberrations or sister chromatid exchange, including some studies with positive-exposure response trends. There are eight studies of cancer mortality or incidence among highly exposed workers; most are cohort studies of lead smelter or battery workers exposed decades ago. METHODS: We reviewed the epidemologic studies with regard to cancer. RESULTS: These studies provide some evidence of increased risk of lung cancer (RR = 1.30, 1.15-1.46, 675 observed deaths) and stomach cancer (combined RR = 1.34, 1.14-1.57, 181 observed). However, the lung cancer findings are not consistent across studies, and confounding by arsenic may affect the study with the highest lung cancer RR. Exclusion of that study yields a combined lung cancer RR of 1.14 (1.04-1.73). There is little evidence of increased risk of kidney cancer (combined RR = 1.01, 0. 72-1.42, 40 observed) or brain cancer (combined RR = 1.06, 0.81-1.40, 69 observed). However, two studies show a two-fold increase in kidney cancer, and one study shows a significant excess of gliomas. IARC classified lead as a "possible human carcinogen" based on sufficient animal data and insufficient human data in 1987. Six of the eight studies cited above have been published since 1987. CONCLUSIONS: Overall, there is only weak evidence associating lead with cancer; the most likely candidates are lung cancer, stomach cancer, and gliomas.
Animals↗
Tomatoes, tomato-rich foods, lycopene and cancer of the upper aerodigestive tract: a case-control in Uruguay.
In order to study the relationship between tomatoes, tomato products, lycopene and cancers of the upper aerodigestive tract (UADC; oral cavity, pharynx, larynx, esophagus) a case-control study was carried out in Uruguay, in the time period 1996-98. Two-hundred and thirty eight cases and 491 hospitalized controls were frequency matched on age, sex, residence and urban/rural status. Both series were submitted to a detailed questionnaire, including tobacco smoking, alcohol drinking and queries on 64 food items. These data were analyzed by unconditional logistic regression, after adjusting by total energy intake. Tomato intake was associated with a reduction in risk of 0.30 (95% confidence interval [CI], 0.18-0.51), whereas tomato sauce-rich foods displayed a protective effect of 0.57 (95% CI, 0.33-0.96 for the highest quartile of intake). The food group composed of raw tomato and tomato-rich foods showed a strong inverse association with UADC (odds ratio [OR], 0.23; 95% CI, 0.13-0.39 for the highest quartile of intake). Lycopene was also strongly associated with a reduced risk of 0.22 (95% CI, 0.13-0.37). Adjustment of tomato intake for several phytochemicals explained almost completely its protective effect, which disappears in this model. Finally, the joint effect of lycopene and total phytosterols was associated with a significant reduction in risk (OR, 0.11; 95% CI, 0.05-0.23).
Adult↗
Environmental exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.
A number of epidemiological studies have addressed the risk of pleural mesothelioma from environmental (household and neighborhood) exposure to asbestos, but no overall risk estimate is available. We reviewed the epidemiological studies on risk of pleural mesothelioma and household or neighborhood exposure to asbestos. We identified eight relevant studies; most were conducted in populations with relatively high exposure levels. We combined the risk estimates in a meta-analysis based on the random-effects model. The relative risks (RRs) of pleural mesothelioma for household exposure ranged between 4.0 and 23.7, and the summary risk estimate was 8.1 (95% confidence interval [CI]: 5.3-12). For neighborhood exposure, RRs ranged between 5.1 and 9.3 (with a single RR of 0.2) and the summary estimate was 7.0 (95% CI: 4.7-11). This review suggests a substantial increase in risk of pleural mesothelioma following high environmental exposure to asbestos; however, the available data are insufficient to estimate the magnitude of the excess risk at the levels of environmental exposure commonly encountered by the general population in industrial countries.
Asbestos↗
Kidney cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies.
OBJECTIVE: To study the risk of kidney cancer following asbestos exposure. METHODS: We carried out a meta-analysis of the results of cohort studies of workers predominantly exposed to asbestos. We contacted the authors of 70 cohort studies; published results were available from the reports of 10 cohorts; we obtained the relevant information for an additional 27 cohorts. RESULTS: The studies included in the analysis comprised a total of 169 kidney cancer deaths and 69 incident cases. The overall pooled standardized mortality ratio (SMR) of kidney cancer was 1.1, with a 95% confidence interval (95% CI) of 0.9-1.3. The pooled SMR was higher for workers with undefined asbestos exposure (SMR 1.2, 95% CI 0.9-1.6) than for workers with either predominant chrysotile (SMR 0.9, 95% CI 0.7-1.3) or some amphibole (SMR 0.96, 95% CI 0.6-1.5) exposure. Studies with published results had higher SMRs than studies for which information was obtained from the authors. Studies with high asbestos exposure and an elevated SMR of lung cancer tended to show an increased risk of kidney cancer. CONCLUSIONS: It is unlikely that asbestos exposure is responsible for an important increase in kidney cancer risk; however, high asbestos exposure might entail a small increase in risk.
Adult↗
A multicenter case-control study of diet and lung cancer among non-smokers.
OBJECTIVE: We have examined the role of dietary patterns and specific dietary nutrients in the etiology of lung cancer among non-smokers using a multicenter case-control study. METHODS: 506 non-smoking incident lung cancer cases were identified in the eight centers along with 1045 non-smoking controls. Dietary habits were assessed using a quantitative food-frequency questionnaire administered by personal interview. Based on this information, measures of total carotenoids, beta-carotene and retinol nutrient intake were estimated. RESULTS: Protective effects against lung cancer were observed for high consumption of tomatoes, (odds ratio (OR) = 0.5; 95% confidence interval (CI) 0.4-0.6), lettuce (OR = 0.6; 95% CI 0.3-1.2), carrots (OR = 0.8; 95% CI 0.5-1.1), margarine (OR = 0.7; 95% CI 0.5-0.8) and cheese (OR = 0.7; 95% CI 0.5-1.0). Only weak protective effects were observed for high consumption of all carotenoids (OR = 0.8; 95% CI 0.6-1.0), beta-carotene (OR = 0.8; 95% CI 0.6-1.1) and retinol (OR = 0.9; 95% CI 0.7-1.1). Protective effects for high levels of fruit consumption were restricted to squamous cell carcinoma (OR = 0.7; 95% CI 0.4-1.2) and small cell carcinoma (OR = 0.7; 95% CI 0.4-1.2), and were not apparent for adenocarcinoma (OR = 0.9; 95% CI 0.6-1.3). Similarly, any excess risk associated with meat, butter and egg consumption was restricted to squamous and small cell carcinomas, but was not detected for adenocarcinomas. CONCLUSIONS: This evidence suggests that the public health significance of increasing vegetable consumption among the bottom third of the population would include a reduction in the incidence of lung cancer among lifetime non-smokers by at least 25%, and possibly more. A similar protective effect for increased fruit consumption may be present for squamous cell and small cell lung carcinomas.
Adenocarcinoma↗
Employment as butcher and cancer risk in a record-linkage study from Sweden.
OBJECTIVE: To investigate the risk of cancer among butchers and other meat workers in a large record-linkage study from Sweden. METHODS: The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971-1989 for all residents, by occupation and industry of employment as reported at the 1960 and 1970 censuses. We identified 25,049 men classified as butchers or meat workers at either census. We used as a comparison group the remaining part of the active male population, after exclusion of workers with direct contact with animals. RESULTS: Butchers in the meat industry had a slight increase in the risk of cancer (relative risk [RR] 1.1, 95% confidence interval [CI] 1.0-1.3), which was due to an increased risk of cancers of the oral cavity and pharynx (RR 1.6, 95% CI 1.0-2.7), stomach (RR 1.6, 95% CI 1.1-2.7), larynx (RR 1.4, 95% CI 0.6-3.4), and lung (RR 1.4, 95% CI 1.1-1.9). The risk of stomach cancer was highest during the first 5 years of the study, and among butchers from urban areas. No temporal or geographic variations were seen for lung cancer risk, with elevations restricted to squamous cell carcinoma. An increased risk of stomach, laryngeal and lung cancers was present in butchers and meat workers outside the meat industry. There was no clear indication of an increased risk of other neoplasms. CONCLUSIONS: The increased risk of oral, laryngeal, lung and stomach cancers among Swedish butchers may be at least partly due to confounding by tobacco smoking, alcohol drinking, and other lifestyle factors. However, exposures in the meat industry (e.g., viruses, nitrosamines, polycyclic aromatic hydrocarbons) may contribute the elevated cancer risks.
Adolescent↗
Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case-control studies in European countries.
BACKGROUND: Coffee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coffee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case-control studies. METHODS: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coffee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. RESULTS: Seventy-nine percent of the study population reported having drunk coffee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coffee drinkers (OR = 1.0, 95% CI 0.8-1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically significant excess risk was seen for subjects having drunk ten or more cups per day (OR = 1.8, 95% CI 1.0-3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coffee consumption. The pooled results were not dependent on the findings of any specific study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. CONCLUSION: Nonsmokers who are heavy coffee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coffee drinking.
Bias↗
Molecular epidemiology.
The use of biomarkers in epidemiology is not new, but recent developments in molecular biology and genetics have increased the opportunities for their use. However, epidemiological studies based on biomarkers, which belong to the discipline defined as 'molecular epidemiology' are subject to the same problems of design and analysis as 'traditional' epidemiological studies. If biomarkers offer new opportunities to overcome some of the limitations of epidemiology, their added value over traditional approaches should be systematically assessed. Biomarkers should be validated though transitional studies; consideration to sources of bias and confounding in molecular epidemiology studies should be no less stringent than in traditional studies.
Bias↗
Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy.
Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case-control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8-20.3) than among women (OR = 4.2, CI 3.5-5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0-19, 20-39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6-4.2], 4.1 [CI 3.1-5.6]) and women (OR = 1.0, 2.7 [CI 1.7-4.1], 3.3 [CI 1.9-5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men.
Adenocarcinoma↗
Second primary neoplasms following non-Hodgkin's lymphoma in New South Wales, Australia.
The incidence of non-Hodgkin's lymphoma (NHL) has been increasing rapidly over the last three decades. The reasons for this trend are not known although increasing exposure to sunlight has been postulated. We used data from the New South Wales Central Cancer Registry to analyse second primary neoplasms following NHL diagnosed between 1972 and 1995, to identify possible common causal agents. A total of 12,452 patients contributed 54,308 person-years of follow-up during which time there were 705 second primary neoplasms compared to 592.99 expected (standardized incidence ratio (SIR = 1.19, 95% confidence interval (CI) 1.10-1.28). There were excesses of melanomas of skin (SIR = 2.38, 95% CI 1.92-2.91), lip cancer (SIR = 2.74, 95% CI 1.59-4.38), tongue cancer (SIR = 2.53, 95% CI 1.09-4.99) and bladder cancer (SIR = 1.64, 95% CI 1.19-2.21). There was also over a threefold excess in soft tissue sarcomas (SIR = 3.61, 95% CI 1.80-6.45) and in thyroid cancer (SIR = 3.42, 95% CI 1.56-6.49). The SIR for myeloid leukaemia was 0.78 (95% CI 0.28-1.69). The increases in melanoma of the skin and cancer of the lip and tongue among patients with NHL strongly suggest sunlight exposure as a shared causal agent. The increase in soft tissue sarcomas might be due to shared effects of exposure to chemicals such as phenoxy acid herbicides. The increases in bladder and thyroid cancers are likely to be explained by effects of treatment for NHL. We did not find a chemotherapy related increased risk of myeloid leukaemia among NHL patients.
Adult↗
Occupational risks for lung cancer among nonsmokers.
We conducted a case-control study in 12 European study centers to evaluate the role of occupational risk factors among nonsmokers. We obtained detailed occupational histories from 650 nonsmoking cases (509 females/141 males) and 1,542 nonsmoking controls (1,011 females/531 males). On the basis of an a priori definition of occupations and industries that are known (list A) or suspected (list B) to be associated with lung carcinogenesis, we calculated odds ratios (ORs) for these occupations, using unconditional logistic regression models and adjusting for sex, age, and center effects. Among nonsmoking men, an excess relative risk was observed among those who had worked in list-A occupations [OR = 1.52; 95% confidence interval (C) = 0.78-2.97] but not in list-B occupations (OR = 1.05; 95%), CI = 0.60-1.83). Among nonsmoking women, there was an elevation of risk for list-A occupations (OR = 1.50; 95% CI = 0.49-4.53), although this estimate was imprecise, given that less than 1% of cases and controls were exposed. Exposure to list-B occupations was associated with an increase in relative risk (OR = 1.69; 95% CI = 1.09-2.63) in females, but not in males. Women who had been laundry workers or dry cleaners had an OR of 1.83 (95% CI = 0.98-3.40). Our findings confirm that certain occupational exposures are associated with an increased risk for lung cancer among both female and male nonsmokers; however, knowledge on occupational lung carcinogens is biased toward agents to which mainly men are exposed.
Adult↗
Dietary carotenoids and risk of gastric cancer: a case-control study in Uruguay.
In the period 1997-1999, 120 incident and histologically verified cases of stomach cancer were frequency matched on age, sex, residence and urban/rural status with 360 controls in order to study the role of diet in gastric cancer in Uruguay. Our attention was focused on the role of carotenoids in gastric carcinogenesis, after controlling for major confounders. According to the results, vitamin A, alpha-carotene and lycopene were associated with strong inverse relationships with stomach cancer (OR of stomach cancer for high alpha-carotene intake 0.34, 95% CI 0.17-0.65). Joint exposure to high intakes of alpha-carotene and vitamin C intakes were associated with a strong reduction in risk (OR 0.11, 95% CI 0.03-0.36). It was also suggested that high lycopene intake explained most of the reduction in risk of gastric cancer associated with vegetable intake, whereas no such effect was observed for fruit intake.
Adult↗
Occupational exposures and lung cancer in Buenos Aires, Argentina.
The main objective of this study was to analyze the risks associated with occupational exposures in an industrializing country where lung cancer is the primary neoplastic cause of death in men. A full occupational history was collected through interviewing 199 men with lung cancer and 393 control subjects. Exposure to arsenic, asbestos, chromium, dust, nickel, and polynuclear aromatic hydrocarbons was assessed by means of a job-exposure matrix. Elevated odds ratios were observed for employment in the alcoholic beverages industry (5.2; 95% confidence interval [CI], 1.1 to 23.1), sawmills and wood mills (4.8; 95% CI, 1.2 to 19.0), water transport (3.3; 95% CI, 1.1 to 12.1), and chemicals/plastics manufacturers (1.9; 95% CI, 1.1 to 3.3). A small, non-significant increased risk was observed after long-term exposure to arsenic and chromium, with a dose-response for chromium. Although some of the present results may result from chance, most are consistent with those of previous investigations in other countries.
Adult↗
Occupational exposure to carcinogens in the European Union.
OBJECTIVES: To construct a computer assisted information system for the estimation of the numbers of workers exposed to established and suspected human carcinogens in the member states of the European Union (EU). METHODS: A database called CAREX (carcinogen exposure) was designed to provide selected exposure data and documented estimates of the number of workers exposed to carcinogens by country, carcinogen, and industry. CAREX includes data on agents evaluated by the International Agency for Research on Cancer (IARC) (all agents in groups 1 and 2A as of February 1995, and selected agents in group 2B) and on ionising radiation, displayed across the 55 industrial classes. The 1990-3 occupational exposure was estimated in two phases. Firstly, estimates were generated by the CAREX system on the basis of national labour force data and exposure prevalence estimates from two reference countries (Finland and the United States) which had the most comprehensive data available on exposures to these agents. For selected countries, these estimates were then refined by national experts in view of the perceived exposure patterns in their own countries compared with those of the reference countries. RESULTS: About 32 million workers (23% of those employed) in the EU were exposed to agents covered by CAREX. At least 22 million workers were exposed to IARC group 1 carcinogens. The exposed workers had altogether 42 million exposures (1.3 mean exposures for each exposed worker). The most common exposures were solar radiation (9.1 million workers exposed at least 75% of working time), environmental tobacco smoke (7.5 million workers exposed at least 75% of working time), crystalline silica (3.2 million exposed), diesel exhaust (3.0 million), radon (2.7 million), and wood dust (2.6 million). CONCLUSION: These preliminary estimates indicate that in the early 1990s, a substantial proportion of workers in the EU were exposed to carcinogens.
Carcinogens↗
Occupational exposures and pancreatic cancer: a meta-analysis.
OBJECTIVES: Consolidation of epidemiological data on pancreatic cancer and worksite exposures. METHODS: Publications during 1969-98 were surveyed. Studies without verified exposures were excluded. Meta-analyses were conducted on data from 92 studies covering 161 populations, with results for 23 agents or groups of agents. With a standard format, five epidemiologists extracted risk estimates and variables of the structure and quality of each study. The extracted data were centrally checked. Random meta-models were applied. RESULTS: Based on 20 populations, exposure to chlorinated hydrocarbon (CHC) solvents and related compounds was associated with a meta-risk ratio (MRR) of 1.4 (95% confidence interval (95% CI) 1.0 to 1.8). Nickel and nickel compounds were considered in four populations (1.9; 1.2 to 3.2). Excesses were found also for chromium and chromium compounds (1.4; 0.9 to 2.3), polycyclic aromatic hydrocarbons (PAHs) (1.5; 0.9 to 2.5), organochlorine insecticides (1.5; 0.6 to 3.7), silica dust (1.4; 0.9 to 2.0), and aliphatic and alicyclic hydrocarbon solvents (1.3; 0.8 to 2.8). Evidence on pancreatic carcinogenicity was weak or non-positive for the following agents: acrylonitrile (1.1; 0.0 to 6.2); arsenic (1.0; 0.6 to 1.5); asbestos (1.1; 0.9 to 1.5); diesel engine exhaust (1.0; 0.9 to 1.3); electromagnetic fields (1.1; 0.8 to 1.4); formaldehyde (0. 8; 0.5 to 1.0); flour dust (1.1; 0.3 to 3.2); cadmium and cadmium compounds (0.7; 0.4 to 1.4); gasoline (1.0; 0.8 to 1.2); herbicides (1.0; 0.8 to 1.3); iron and iron compounds (1.3; 0.7 to 2.5); lead and lead compounds (1.1; 0.8 to 1.5); man-made vitreous fibres (1.0; 0.6 to 1.6); oil mist (0.9; 0.8 to 1.0); and wood dust (1.1; 0.9 to 2.5). The occupational aetiological fraction of pancreatic cancer was estimated at 12%. In a subpopulation exposed to CHC solvents and related compounds, it was 29%; to chromium and chromium compounds, 23%; to nickel and nickel compounds, 47%; to insecticides, 33%; and to PAHs, 33%. CONCLUSION: Occupational exposures may increase risk of pancreatic cancer. High quality studies are called for on interactions between occupational, environmental, and lifestyle factors as well as interactions between genes and the environment.
Air Pollutants, Occupational↗
Mortality from cancer and chronic respiratory diseases among workers who manufacture carbon electrodes.
OBJECTIVES: To investigate the risk of cancer and non-neoplastic respiratory diseases among workers who manufacture carbon electrodes, as this industry entails exposure to mixtures of polycyclic aromatic hydrocarbons. METHODS: A historical cohort study was carried out of 1006 male workers employed for at least 1 year between 1945 and 1971 in a carbon (graphite) electrode production plant in central Italy, who were followed up for mortality between 1955 and 1996. The ratio of observed to expected deaths (standardised mortality ratios, SMRs) was computed from both national and (for the period 1964-96) regional age and period specific mortalities. A multivariate Poisson regression analysis was performed to investigate the relative risk (RR) of death according to duration of employment and time since first employment in the factory. RESULTS: A total of 424 workers had died, 538 were still alive, and 44 were lost to follow up. Mortalities from all causes, all cancers, and respiratory tract cancer were in line with the regional figure. An excess was found over the expected deaths from skin cancer including melanoma (SMR 3.16, 95% confidence interval (95% CI) 0.65 to 9.23) and from non-neoplastic respiratory diseases (SMR 1.58, 95% CI 1.16 to 2.11). Poisson regression analysis including age as a covariate showed an increased risk of dying from gastric cancer with increasing duration of employment, and an increase in the RR of dying from lung cancer and from non-neoplastic respiratory diseases with increasing time since first employment, although the linear trend was not significant. CONCLUSION: This study supports previous findings that working in the carbon electrode manufacturing industry may not increase the risk of dying from respiratory cancer. However, a possible association with non-malignant respiratory diseases cannot be excluded.
Adult↗
Plant sterols and risk of stomach cancer: a case-control study in Uruguay.
In 1997-1999, 120 incident and histologically verified cases of stomach cancer were frequency matched on age, gender, residence, and urban/rural status with 360 controls to study the role of diet in gastric cancer in Uruguay. We focused on the role of plant sterols (beta-sitosterol, campesterol, stigmasterol, and total plant sterols) after controlling for major confounders. Total phytosterols were associated with a strong inverse relationship with stomach cancer (odds ratio of stomach cancer for total phytosterol intake in the highest tertile = 0.33, 95% confidence interval = 0.17-0.65). Joint exposure to high intake of total phytosterol and alpha-carotene was also inversely associated with gastric cancer risk (odds ratio = 0.09, 95% confidence interval = 0.02-0.32). High intake of total plant sterols explained most of the attenuation in risk of gastric cancer associated with vegetable and fruit intakes.
Adult↗