Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glassworks area.

BACKGROUND: Production of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer. OBJECTIVE: The aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors. METHODS: The study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979-2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer. RESULTS: Despite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms. CONCLUSIONS: The associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

Challenges in assessing the health risks of consuming vegetables in metal-contaminated environments.

A great deal of research has been devoted to the characterization of metal exposure due to the consumption of vegetables from urban or industrialized areas. It may seem comforting that concentrations in crops, as well as estimated exposure levels, are often found to be below permissible limits. However, we show that even a moderate increase in metal accumulation in crops may result in a significant increase in exposure. We also highlight the importance of assessing exposure levels in relation to a regional baseline. We have analyzed metal (Pb, Cd, As) concentrations in nearly 700 samples from 23 different vegetables, fruits, berries and mushrooms, collected near 21 highly contaminated industrial sites and from reference sites. Metal concentrations generally complied with permissible levels in commercial food and only Pb showed overall higher concentrations around the contaminated sites. Nevertheless, probabilistic exposure assessments revealed that the exposure to all three metals was significantly higher in the population residing around the contaminated sites, for both low-, median- and high consumers. The exposure was about twice as high for Pb and Cd, and four to six times as high for As. Since vegetable consumption alone did not result in exposure above tolerable intakes, it would have been easy to conclude that there is no risk associated with consuming vegetables grown near the contaminated sites. However, when the increase in exposure is quantified, its potential significance is harder to dismiss - especially when considering that exposure via other routes may be elevated in a similar way.

Increased Cancer Incidence in the Local Population Around Metal-Contaminated Glassworks Sites.

OBJECTIVE: The aim of this study was to examine mortality causes and cancer incidence in a population cohort that have resided in close proximity to highly metal-contaminated sources, characterized by contamination of, in particular, arsenic (As), cadmium (Cd), and lead (Pb). METHODS: Data from Swedish registers were used to calculate standardized mortality and cancer incidence ratios. An attempt to relate cancer incidence to metal contamination levels was made. RESULTS: Significantly elevated cancer incidences were observed for overall malignant cancers in both genders, cancer in the digestive system, including colon, rectum, and pancreas, and cancers in prostate among men. Dose-response relationships between Cd and Pb levels in soil and cancer risks were found. CONCLUSIONS: Cancer observations made, together with previous studies of metal uptake in local vegetables, may imply that exposure to local residents have occurred primarily via oral intake of locally produced foodstuffs.

Alterations in high-density lipoprotein proteome and function associated with persistent organic pollutants.

There is a growing body of evidence that persistent organic pollutants (POPs) may increase the risk for cardiovascular disease (CVD), but the mechanisms remain unclear. High-density lipoprotein (HDL) acts protective against CVD by different processes, and we have earlier found that HDL from subjects with CVD contains higher levels of POPs than healthy controls. In the present study, we have expanded analyses on the same individuals living in a contaminated community and investigated the relationship between the HDL POP levels and protein composition/function. HDL from 17 subjects was isolated by ultracentrifugation. HDL protein composition, using nanoliquid chromatography tandem mass spectrometry, and antioxidant activity were analyzed. The associations of 16 POPs, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, with HDL proteins/functions were investigated by partial least square and multiple linear regression analysis. Proteomic analyses identified 118 HDL proteins, of which ten were significantly (p<0.05) and positively associated with the combined level of POPs or with highly chlorinated PCB congeners. Among these, cholesteryl ester transfer protein and phospholipid transfer protein, as well as the inflammatory marker serum amyloid A, were found. The serum paraoxonase/arylesterase 1 activity was inversely associated with POPs. Pathway analysis demonstrated that up-regulated proteins were associated with biological processes involving lipoprotein metabolism, while down-regulated proteins were associated with processes such as negative regulation of proteinases, acute phase response, platelet degranulation, and complement activation. These results indicate an association between POP levels, especially highly chlorinated PCBs, and HDL protein alterations that may result in a less functional particle. Further studies are needed to determine causality and the importance of other environmental factors. Nevertheless, this study provides a first insight into a possible link between exposure to POPs and risk of CVD.

Exposure and body burden of polychlorinated biphenyls (PCB) and metals in a historically contaminated community.

There are many small villages where environmental contamination is substantial due to historical industrial activities. The aim of the present study was to investigate if long-term or current consumption of local foods, as reported in food frequency questionnaires, co-vary with measured concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), lead (Pb), cadmium (Cd) and mercury (Hg) in blood, urine and hair from a population living in a historically contaminated village. Blood, urine and hair were provided by men (n=38) and women (n=57), who had participated in a previous case-control study in the contaminated area, and were analyzed for PCB, OCPs, Pb, Cd and Hg. A detailed food frequency questionnaire, used in the previous epidemiological study, was repeated, and up-dated information of life-style, exposure factors and other covariates was collected. Associations between reported consumption of local foods and exposure biomarkers were explored in relation to age, gender, life-style factors and other covariates. A large part of the population in the area reported consumption of local food, and thus, was potentially exposed to the contaminants. Despite the limited number of participants and other weaknesses described, it was possible to link reported consumption of different foods to biomarker concentrations. Reported consumption of local vegetables, forest berries and mushrooms co-varied with urinary Cd, indicating an influence from the contaminated area on the Cd exposure. We found no associations between PCB plasma concentrations with reported consumption of local fish, but with consumption of herring (non-local sea fish) which is typically high in PCB. Pesticide (HCB, p,p'-DDE, trans-nonachlor) exposure was mainly associated with agricultural work and having a private well the first five years of life, but we found no associations between pesticide concentrations in plasma and consumption of local vegetables or fish. Exposure to Hg was associated with consumption of fish, both local and non-local, and Pb exposure was associated with the consumption of game. Overall, the contaminant concentrations measured in blood, urine and hair varied substantially among study participants, but on average, the concentrations were similar to concentrations measured in other groups of the general Swedish population in the same age range. Larger studies are needed to evaluate health risks (and causality) associated with historical environmental contamination.

Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer.

Persistent organic pollutants (POPs) are lipophilic environmental toxins that have been associated with cardiovascular disease (CVD) and cancer. The aim of this study was to investigate the concentrations of POPs in human high and low/very low-density lipoproteins (HDL and LDL/VLDL) and the possible association with CVD and cancer occurrence in individuals living in a contaminated area. Lipoproteins from 28 individuals (7 healthy controls, 8 subjects with cancer, 13 subjects with CVD) were isolated and the fraction-specific concentration of 20 different POPs was analyzed by high resolution gas chromatography/high resolution mass spectrometry. The activity of Paraoxonase 1 (PON1), an anti-oxidant in HDL, was determined in plasma of these 28 subjects and additional 50 subjects from the same area excluding diseases other than cancer or CVD. Fourteen polychlorinated biphenyls (PCBs) and three organochlorine pesticides were detected, and especially highly chlorinated PCBs were enriched in lipoproteins. Significantly higher concentrations of POPs were found among individuals with CVD or cancer compared to controls. Principal component analyses showed that POP concentrations in HDL were more associated with CVD, while POP concentrations in LDL/VLDL were more associated with cancer. PON1 activity was negatively correlated to sumPCB and a co-variation between decreased arylesterase-activity, increased PCB concentrations and CVD was found. This study shows that POPs are present in lipoproteins and were more abundant in individuals with CVD or cancer compared to healthy controls. The results also indicate that PCB exposure is accompanied by reduced PON1 activity that could impair the HDL function to protect against oxidation.

Health effects and exposure to polychlorinated biphenyls (PCBs) and metals in a contaminated community.

Environmental measurements carried out by local authorities during the 1970s, 80s and 90s in an area contaminated by hundreds of years of industrial activities have revealed high levels of zinc (Zn), copper (Cu), lead (Pb) and cadmium (Cd) in soil, vegetables, root crops, berries and mushrooms. In 1972, a large quantity of oil contaminated with polychlorinated biphenyls (PCBs) was accidentally spilled into the river running through the village. To investigate the possible health effects of exposure from local sources, all cancer diagnoses, registered in 1960-2003 for individuals living in the study area, were collected from the regional cancer register of southeast Sweden. The total cancer incidence was non-significantly decreased both among males and females as compared to national rates (SIR=0.91) for each gender. Among males, increased risks, of border-line significance, were seen for testicular cancer and lymphomas as well as significantly decreased risks for cancer in the rectum, respiratory system and brain. Information on lifetime residence, occupation, smoking habits, diseases, childbirth and food consumption, was collected via questionnaires from cancer cases and randomly selected controls. In both genders combined, significant associations were found for total cancer and high consumption of local perch, and for lymphomas and high consumption of both perch and pikeperch. Female breast cancer was significantly associated with high consumption of local perch and pike as well as with work in metal production. Mothers residing in the parish before the age of five reported significantly more preterm child deliveries. In spite of study limitations, the results indicate that residing in a rural contaminated area may contribute to the development of certain cancers and reproductive effects. In females, high consumption of local fish was shown to be the strongest determinant for total cancer, while in males, the strongest determinant was residing in the study area the first five years of life. Further research including validation of exposure using biomarkers is required to verify the findings as well as future studies in other polluted areas in Sweden with larger population bases.

Nutritional and toxicological aspects of seafood consumption--an integrated exposure and risk assessment of methylmercury and polyunsaturated fatty acids.

Seafood consumption is associated with both risks and beneficial effects to human health. Consequently, an integrated exposure assessment of intake of toxic and nutritious agents in seafood is of importance prior to determination of dietary advisories. We have developed a probabilistic model for the estimation of simultaneous intake of methylmercury (MeHg) and long-chain n-3 polyunsaturated fatty acids (LC-n3 PUFAs) from seafood, to estimate the population proportion at risk for exceeding tolerable MeHg intake and not reaching adequate intake of PUFAs. Seafood consumption data was collected among women of childbearing age using a food frequency questionnaire. A database of mercury and fatty acids concentration in seafood was constructed. A Latin Hypercube simulation was used to calculate the intake of MeHg and LC n-3 PUFAs. Eleven percent of the population exceeded the MeHg reference dose of 0.1 µg/kg bw/day, whereas only 44% reached an adequate PUFA intake. A small proportion (3.7%) exceeded the MeHg reference dose while at the same time did not reach an adequate PUFA intake. Furthermore, we simulated two scenarios in which seafood is consumed according to a general recommendation of three servings per week, whereof one serving of oily seafood. The first scenario included seafood with typically low MeHg concentrations (mean 0.056 and 0.027 µg MeHg/g fish in lean and oily species, respectively), and the second included seafood typically high in MeHg concentrations (mean 0.50 and 0.26 µg MeHg/g fish in lean and oily species, respectively). In the "high"scenario, almost 100% of the population exceeded the reference dose, whereas the corresponding proportion was only 5% in the "low" scenario. Overall, the results stress the importance of communicating species specific seafood consumption advisories for women of childbearing age in general and for pregnant women in particular, while at the same time encourage them to consume more seafood.