| 1. |
- Vermeulen, Roel, et al.
(författare)
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Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma : univariate and functionally informed multivariate analyses
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:6, s. 1335-1347
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Tidskriftsartikel (refereegranskat)abstract
- Recent prospective studies have shown that dysregulation of the immune system may precede the development of B‐cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case–control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01–15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor‐2 (FGF‐2 p = 7.2 × 10−4) and transforming growth factor alpha (TGF‐α, p = 6.5 × 10−5) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF‐2 (p = 7.8 × 10−7), TGF‐α (p = 4.08 × 10−5), fractalkine (p = 1.12 × 10−3), monocyte chemotactic protein‐3 (p = 1.36 × 10−4), macrophage inflammatory protein 1‐alpha (p = 4.6 × 10−4) and vascular endothelial growth factor (p = 4.23 × 10−5). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case‐only analyses showed that Granulocyte‐macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth‐factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL.
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| 2. |
- Engström, Karin, et al.
(författare)
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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
- 2011
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
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Tidskriftsartikel (refereegranskat)abstract
- Background: 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. Methods: 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. Results: 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. Conclusions: 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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| 3. |
- Engström, Karin, et al.
(författare)
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Genetic variation in glutathione-related genes and body burden of methylmercury
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - Research Triangle Park, N.C. : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:6, s. 734-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p = 0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p = 0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism.
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| 4. |
- Lundh, Thomas, et al.
(författare)
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Spårelement i blodkroppar från väster- och norrbottningar 1990-99
- 2002
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sexton spårelement bestämdes i blodkroppar från 600 kvinnor och män i åldrarna 25-74 år från Västerbotten och Norrbotten. Med Induktiv kopplad plasma (ICP-MS) bestämdes aluminium (Al), vanadin (V), mangan (Mn), kobolt (Co), nickel (Ni), koppar (CU), zink (Zn), selen (Se), rodium (Rh), palladium (Pd), kadmium (Cd), antimon (Sb), wolfram (W), platina (Pt) och bly (Pb). Dessutom bestämdes med atomfluorescens kvicksilver (Hg). Cd-koncentrationerna är av en nivå som kopplats samman med lätt toxicitet. Medianhalterna av Pb och Hg ligger långt under de som satts i samband med toxiska effekter. Variationen var emellertid hög; de högsta halterna är i nivå med dem som anses kunna orsaka ogynnsamma effekter. I en multivariat modell utvärderades effekter av kön, ålder, rökvanor och kalenderår. Framför allt för Cd, men i viss mån också för Hg, hade rökare högre halter än icke-rökare. Kvinnor hade högre halter av Cd och Pb än män. Det fanns klart stigande halter av Cd och Hg med stigande ålder. Vid jämförelse mellan prover tagna 1990, 1994 och 1999 hade en markant sänkning skett av Pb (ca 6% per år), Hg (ca 6% per år) och Cd, men i det fallet bara för män (6% per år), inte för kvinnor. Detta beror sannolikt på minskade utsläpp av dessa metaller, med sjunkande exponering som följd. För Pb och Cd bör sänkningen i exponering ha varit högre än 6% per år, eftersom tidigare ådragen kroppsbörda har en tendens att fördröja en sänkning i blodkroppar. Det finns skäl att även fortsättningsvis följa utvecklingen av metallhalter i blod. För halterna av Al, V, Mn, Co, Ni, Cu, Zn, Se, Rh, Pd, Sb, W och Pt i prover tagna 1999 finns mindre möjligheter att jämföra med andra studier. De funna halterna är emellertid i paritet med det fåtal andra undersökningar som finns. Det fanns en rad associationer mellan halter av olika element. Av särskilt intresse är korrelationerna mellan Pt, Pd and Rh, vilka har spritts i miljön genom användning av katalytiska avgasrenare i bilar. Detta fynd förtjänar vidare undersökningar. Se och Hg var också relaterade, troligen p g a gemensam källa i form av fisk, möjligen också gemensamma bindningar i kroppen.
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| 5. |
- Nilsson Sommar, Johan, et al.
(författare)
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End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden.
- 2013
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Ingår i: Environmental health : a global access science source. - : BioMed Central (BMC). - 1476-069X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Background: 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. Methods: 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. Results: 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. Conclusions: 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.
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| 6. |
- Nilsson Sommar, Johan, et al.
(författare)
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Hip Fracture Risk and Cadmium in Erythrocytes : A Nested Case-Control Study with Prospectively Collected Samples
- 2014
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Ingår i: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 94:2, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have investigated the relation between bone mass density and cadmium exposure, but only few studies have been performed on fractures and biomarkers of cadmium. This study analyzed the association between hip fracture risk and cadmium in erythrocytes (Ery-Cd). Prospective samples from the Northern Sweden Health and Disease Study's biobank were used for 109 individuals who later in life had sustained a low-trauma hip fracture, matched with two controls of the same age and gender. The mean concentration of Ery-Cd (±SD) in case samples was 1.3 ± 1.4 versus 0.9 ± 1.0 μg/L in controls. The odds ratio (OR) was 1.63 [95 % confidence interval (CI) 1.10-2.42] for suffering a hip fracture for each microgram per liter increase in Ery-Cd. However, when taking smoking into consideration (never, former, or current), neither Ery-Cd nor smoking showed a statistically significant increase in fracture risk. Using multiple conditional logistic regression with BMI, height, and smoking, the estimated OR for a 1-μg/L increase in Ery-Cd was 1.52 (95 % CI 0.77-2.97). Subgroup analysis showed an increased fracture risk among women (OR = 1.94, 95 % CI 1.18-3.20, for a 1 μg/L increase), which also remained in the multiple analysis (OR = 3.33, 95 % CI 1.29-8.56). This study shows that fracture risk is associated with Ery-Cd. It is, however, not possible to draw firm conclusions on whether cadmium is the causal factor or whether other smoking-related factors cause this association. Subgroup analysis shows that cadmium is a risk factor for hip fracture among women.
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| 7. |
- Wennberg, Maria, 1974-, et al.
(författare)
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Fish consumption and myocardial infarction : a second prospective biomarker study from northern Sweden
- 2011
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Ingår i: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 93:1, s. 27-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: A beneficial role of fish consumption on the risk of myocardial infarction (MI) has been reported, mostly ascribed to n-3 fatty acids. However, fish also contains methylmercury, which may increase the risk of MI.Objective: Describe 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 acid) in plasma phospholipids (P-EPA+DHA) are protective.Design: This is a case-control study nested within the northern Sweden cohort with prospectively collected data and samples. It comprises 431 cases with an MI after data and sample collection, including 81 sudden cardiac deaths (SCD), and 499 matched controls. Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses.Results: Odds ratio (OR) for the third tertile versus the first were for Ery-Hg: 0.65 (95% CI: 0.46, 0.91); Ery-Se: 0.75 (95% CI: 0.53, 1.06) and P-EPA+DHA: 0.78 (95% CI: 0.54, 1.11). No association was seen for reported fish consumption. Multivariate modelling did not change these associations significantly. Sex-specific analyses revealed no differences in risk associations for Ery-Hg, but a tendency to a higher protective association with P-EPA+DHA for women. High levels of Ery-Se were associated with increased risk of SCD.Conclusions: Ery-Hg, a stable biomarker for fish consumption, is associated with a decreased risk of MI. The result indicates a protective effect of fish consumption against MI, even though data on self-reported fish consumption do not reveal any clear protective association.
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| 8. |
- Wennberg, Maria, 1974-, et al.
(författare)
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Fish intake, mercury, long-chain n-3 polyunsaturated fatty acids and risk of stroke in northern Sweden
- 2007
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 98:5, s. 1038-1045
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Tidskriftsartikel (refereegranskat)abstract
- Results of previous studies on fish intake and stroke risk have been inconclusive. Different stroke types have often not been separated. Our aim was to elucidate whether intake of fish, Hg or the sum of proportions of fatty acids EPA (20:5n-3) and DHA (22: 6n-3) influence the risk of haemorrhagic or ischaemic stroke. Within a population-based cohort from a community intervention programme, 369 stroke cases and 738 matched controls were identified and included in the present nested case-control study. Information on fish intake had been recorded at recruitment, i.e. before diagnosis. Hg levels were determined in erythrocyte membranes, also collected at recruitment, and the relative content of fatty acids was measured in erythrocyte membranes or plasma phospholipids. The results showed that in women there was a non-significant decrease in stroke risk with increasing fish intake (OR 0·90 (95 % CI 0·73, 1-11) per meal per week). The risk in women differed significantly (P=0·03) from that in men, in whom the OR for stroke rose with increasing fish intake (OR 1·24 (95 % CI 1·01, 1·51) per meal per week). The corresponding risk in men for Hg was 0·99 (95 % CI 0·93, 1·06), and for the sum of proportions of EPA and DHA 1·08 (95 % CI 0·92, 1·28). We conclude that the relationship between stroke risk and fish intake seems to be different in men and women. Increased levels of EPA and DHA do not decrease the risk for stroke and there is no association between stroke risk and Hg at these low levels.
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| 9. |
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