Cadmium (Cd) and lead (Pb) are hypothesised to be risk factors for non-Hodgkin's lymphoma (NHL), a group of haematological malignancies with a suspected environmental aetiology. Within the EnviroGenoMarkers study we utilised pre-diagnostic erythrocyte concentrations of Cd and Pb to determine whether exposure was associated with risk of B-cell NHL and multiple myeloma.
194 incident cases of B-cell NHL and 76 cases of multiple myeloma diagnosed between 1990 and 2006 were identified from two existing cohorts; EPIC-Italy and the Northern Sweden Health and Disease Study. Cases were matched to healthy controls by centre, age, gender and date of blood collection. Cd and Pb were measured in blood samples provided at recruitment using inductively coupled plasma-mass spectrometry. Logistic regression was applied to assess the association with risk. Analyses were stratified by cohort and gender and by subtype where possible.
There was little evidence of an increased risk of B-cell NHL or multiple myeloma with exposure to Cd (B-cell NHL: OR 1.09 95%CI 0.61, 1.93, MM: OR 1.16 95% CI: 0.40, 3.40 ) or Pb (B-cell NHL: 0.93 95% CI 0.43, 2.02, multiple myeloma: OR 1.63 95%CI 0.45, 5.94) in the total population when comparing the highest to the lowest quartile of exposure. However, gender and cohort specific differences in results were observed. In females the risk of B-cell NHL was more than doubled in those with a body burden of Cd >1 ?g/L (OR 2.20 95%CI; 1.04, 4.65).
This nested case-control study does not support a consistent positive association between Cd or Pb and NHL, but there is some indication of a gender specific effect suggesting further research is warranted.
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Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case-control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition - Italy (EPIC-Italy) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma-mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models with each study result weighted by the within- and between-study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut-points, cadmium levels were not associated with breast cancer risk in the CPS-II cohort (continuous RR = 1.01, 95% CI 0.76-1.34), but were inversely associated with risk in the EPIC- Italy (continuous RR = 0.80, 95% CI 0.61-1.03) and NSHDS cohorts (continuous RR = 0.73, 95% CI 0.54-0.97). The inverse association was also evident in the meta-analysis (continuous RR = 0.84, 95% CI 0.69-1.01) with low between-study heterogeneity. Large differences in lead level distributions precluded a meta-analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta-analysis.
OBJECTIVES: The aim of the study was to investigate cancer risk following employment in the asphalt industry. METHODS :Cancer incidence was studied among 22 362 male asphalt workers employed for more than one season in jobs entailing exposure to bitumen (mainly road pavers) in Denmark, Finland, Norway, and Sweden. These workers are part of a European cohort of asphalt workers, for which results on mortality have been reported. The follow-up was almost complete, and reference rates were obtained from national cancer registries. RESULTS: The incidence of cancer was reduced in all four countries [overall standardized incidence ratio (SIR) 0.89, 95% confidence interval (95% CI) 0.86-0.94]. Lung cancer incidence was increased in all four countries, yielding an overall SIR of 1.21 (95% CI 1.07-1.36), but no trend was detected according to time since first employment. No overall increased incidence of bladder cancer was observed, but there was a suggestion of a tendency towards higher risk with longer time since first employment, with a relative risk of 1.85 (95% CI 0.90-3.78) for more than 30 years versus 1-14 years (P-value for trend 0.1). The incidence of lip and stomach cancer was nonsignificantly increased, and the excess was present mainly in Denmark. No increased incidence was detected for other neoplasms, notably malignant melanoma, nonmelanoma skin cancer, and kidney cancer. CONCLUSIONS: The results of this study confirm the pattern of cancer risk detected in the mortality analysis of the European cohort; in addition, they provide suggestive evidence of an excess risk of bladder cancer among asphalt workers.
Comment In: Scand J Work Environ Health. 2004 Oct;30(5):337-815529796
BACKGROUND: Some studies have indicated an increased risk of lung cancer among asphalt workers. This study investigates the risk of lung cancer in Swedish asphalt workers. METHODS: A cohort of 6,150 asphalt workers, mainly employed in road construction, was compared to the general population, and to a reference group of construction workers not exposed to asphalt fumes. The exposure to polyaromatic hydrocarbons (PAH) at paving in Sweden during the 1980s and 1990s were estimated to be in the order of one or a few micrograms per cubic meter, but must have been higher in earlier years. RESULTS: Thirty-two lung cancer cases were observed among asphalt workers. The relative risk (SIR) and 95% confidence intervals were 0.98 (0.67-1.39). The corresponding relative risk, as compared to a group of construction workers and adjusted for smoking habits, was 1.03 (0.70-1.45). We found no increased risk for other cancers investigated or death in other lung diseases. CONCLUSIONS: Asphalt workers do not have any increased lung cancer risk from exposure to fumes and gases from asphalt at the exposure levels that occurred in Sweden during the 1960s and 1970s.
BACKGROUND: An increased risk of lung cancers among asphalt workers has been suggested in epidemiological studies based on large scale statistical analyses. METHODS: In a multi-country study of 29,820 male workers employed in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers and 17,757 other workers from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality that was documented from 1953-2000. Exposures to bitumen fume, coal tar, 4-6 ring polycyclic aromatic hydrocarbons, organic vapor, diesel exhaust, asbestos, and silica dust were assessed via a job-exposure matrix. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates, as well as relative risks (RRs) based on Poisson regression models were calculated. RESULTS: The SMR of lung cancer among workers exposed to bitumen fume (1.08, 95% CI 0.99-1.18) was comparable to that of non-exposed workers (SMR 1.05, 95% CI 0.92-1.19). In a sub-cohort of bitumen-exposed workers without exposure to coal tar, the SMR of lung cancer was 1.23 (95% CI 1.02-1.48). The analysis based on the semi-quantitative, matrix-based exposures in the whole cohort did not suggest an increased lung cancer risk following exposure to bitumen fume. However, in an analysis restricted to road pavers, based on quantitative estimate of bitumen fume exposure, a dose-response was suggested for average level of exposure, applying a 15-year lag, which was marginally reduced after adjustment for co-exposure to coal tar. The results for cancer of the head and neck were similar to those of lung cancer, although they were based on a smaller number of deaths. There was no clear suggestion of an association with bitumen fume for any other neoplasm. CONCLUSIONS: The results of the analysis by bitumen fume exposure do not allow us to conclude on the presence or absence of a causal link between exposure to bitumen fume and risk of cancer of the lung and the head and neck.
BACKGROUND: Inhalation of bitumen fumes is potentially carcinogenic to humans. METHODS: We conducted a study of 29,820 male workers exposed to bitumen in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers unexposed to bitumen, and 17,757 workers not classifiable as bitumen workers, from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality follow-up during 1953-2000. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates. Poisson regression analyses compared mortality of bitumen workers to that of building or ground construction workers. RESULTS: The overall mortality was below expectation in the total cohort (SMR 0.92, 95% CI 0.90-0.94) and in each group of workers. The SMR of lung cancer was higher among bitumen workers (1.17, 95% CI 1.04-1.30) than among workers in ground and building construction (SMR 1.01, 95% CI 0.89-1.15). In the internal comparison, the relative risk (RR) of lung cancer mortality among bitumen workers was 1.09 (95% CI 0.89-1.34). The results of cancer of the head and neck were similar to those of lung cancer, based on a smaller number of deaths. There was no suggestion of an association between employment in bitumen jobs and other cancers. CONCLUSIONS: European workers employed in road paving, asphalt mixing and other jobs entailing exposure to bitumen fume might have experienced a small increase in lung cancer mortality risk, compared to workers in ground and building construction. However, exposure assessment was limited and confounding from exposure to carcinogens in other industries, tobacco smoking, and other lifestyle factors cannot be ruled out.
Fish consumption and intake of omega-3 fatty acids from fish are associated with a lower risk of cardiovascular disease. However, a prospective study from northern Sweden showed that high consumption of fish is associated with an increased risk of stroke in men, but not in women. The current study aimed to determine if fish consumption is differently related to lifestyle in men compared with women in northern Sweden.
Lifestyle information on 32,782 men and 34,866 women (aged 30-60 years) was collected between 1992 and 2006 within the Västerbotten Intervention Programme (a health intervention in northern Sweden). Spearman correlations coefficients (Rs) were calculated between self-reported consumption of fish and other food items. Lifestyle variables were compared between fish consumption categories.
Fish consumption was positively associated with other foods considered healthy (e.g., root vegetables, lettuce/cabbage/spinach/broccoli, chicken, and berries; Rs = 0.21-0.30), as well as with other healthy lifestyle factors (e.g., exercise and not smoking) and a higher educational level, in both men and women. The only gender difference found, concerned the association between fish consumption and alcohol consumption. Men who were high consumers of fish had a higher intake of all types of alcohol compared with low to moderate fish consumers. For women, this was true only for wine.
Except for alcohol, the association between fish consumption and healthy lifestyle did not differ between men and women in northern Sweden. It is important to adjust for other lifestyle variables and socioeconomic variables in studies concerning the effect of fish consumption on disease outcome.
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Cadmium (Cd), lead (Pb), and mercury (Hg) cause toxicological renal effects, but the clinical relevance at low-level exposures in general populations is unclear. The objective of this study is to assess the risk of developing end-stage renal disease in relation to Cd, Pb, and Hg exposure.
A total of 118 cases who later in life developed end-stage renal disease, and 378 matched (sex, age, area, and time of blood sampling) referents were identified among participants in two population-based prospective cohorts (130,000 individuals). Cd, Pb, and Hg concentrations were determined in prospectively collected samples.
Erythrocyte lead was associated with an increased risk of developing end-stage renal disease (mean in cases 76 µg/L; odds ratio (OR) 1.54 for an interquartile range increase, 95% confidence interval (CI) 1.18-2.00), while erythrocyte mercury was negatively associated (2.4 µg/L; OR 0.75 for an interquartile range increase, CI 0.56-0.99). For erythrocyte cadmium, the OR of developing end-stage renal disease was 1.15 for an interquartile range increase (CI 0.99-1.34; mean Ery-Cd among cases: 1.3 µg/L). The associations for erythrocyte lead and erythrocyte mercury, but not for erythrocyte cadmium, remained after adjusting for the other two metals, smoking, BMI, diabetes, and hypertension. Gender-specific analyses showed that men carried almost all of the erythrocyte lead and erythrocyte cadmium associated risks.
Erythrocyte lead is associated with end-stage renal disease but further studies are needed to evaluate causality. Gender-specific analyses suggest potential differences in susceptibility or in exposure biomarker reliability.
Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction: a case-control study.
The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction.
Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration.
There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously.
No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.
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A beneficial role of fish consumption on the risk of myocardial infarction (MI) has been reported and is mostly ascribed to n-3 (omega-3) fatty acids. However, fish also contains methylmercury, which may increase the risk of MI.
The objective was to determine how fish consumption and erythrocyte concentrations of mercury (Ery-Hg) and selenium (Ery-Se) are related to the risk of MI and whether n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) in plasma phospholipids (P-EPA+DHA) are protective.
This was a case-control study nested within the northern Sweden cohort, in which data and samples were collected prospectively. The study included 431 cases with an MI after data and sample collection, including 81 sudden cardiac deaths (SCDs) and 499 matched controls. Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses.
Odds ratios for the third compared with the first tertile were 0.65 (95% CI: 0.46, 0.91) for Ery-Hg, 0.75 (95% CI: 0.53, 1.06) for Ery-Se, and 0.78 (95% CI: 0.54, 1.11) for P-EPA+DHA. Ery-Hg and P-EPA+DHA were intercorrelated (Spearman's R = 0.34). No association was seen for reported fish consumption. Multivariate modeling did not change these associations significantly. Sex-specific analyses showed no differences in risk associations. High concentrations of Ery-Se were associated with an increased risk of SCD.
The biomarker results indicate a protective effect of fish consumption. No harmful effect of mercury was indicated in this low-exposed population in whom Ery-Hg and P-EPA+DHA were intercorrelated.