27 research outputs found
Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study
Background: Evidence suggests a largely environmental component to non-Hodgkinâs lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined. Methods: The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers. Results: The exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (pâ90th percentile) the association was null for all POPs Conclusion: We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL
Environmental, Dietary, Maternal, and Fetal Predictors of Bulky DNA Adducts in Cord Blood: A European MotherâChild Study (NewGeneris)
Background:Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk.Objective:We selected factors known or hypothesized to affect in utero adduct formation and repair and examined their associations with adduct levels in neonates.Methods:Pregnant women from Greece, Spain, England, Denmark, and Norway were recruited in 2006â2010. Cord blood bulky DNA adduct levels were measured by the 32P-postlabeling technique (n = 511). Diet and maternal characteristics were assessed via questionnaires. Modeled exposures to air pollutants and drinking-water disinfection by-products, mainly trihalomethanes (THMs), were available for a large proportion of the study population.Results:Greek and Spanish neonates had higher adduct levels than the northern European neonates [median, 12.1 (n = 179) vs. 6.8 (n = 332) adducts per 108 nucleotides, p < 0.001]. Residence in southern European countries, higher maternal body mass index, delivery by cesarean section, male infant sex, low maternal intake of fruits rich in vitamin C, high intake of dairy products, and low adherence to healthy diet score were statistically significantly associated with higher adduct levels in adjusted models. Exposure to fine particulate matter and nitrogen dioxide was associated with significantly higher adducts in the Danish subsample only. Overall, the pooled results for THMs in water show no evidence of association with adduct levels; however, there are country-specific differences in results with a suggestion of an association in England.Conclusion:These findings suggest that a combination of factors, including unknown country-specific factors, influence the bulky DNA adduct levels in neonates.Citation:Pedersen M, Mendez MA, Schoket B, Godschalk RW, Espinosa A, Landström A, Villanueva CM, Merlo DF, Fthenou E, Gracia-Lavedan E, van Schooten FJ, Hoek G, Brunborg G, Meltzer HM, Alexander J, Nielsen JK, Sunyer J, Wright J, KovĂĄcs K, de Hoogh K, Gutzkow KB, Hardie LJ, Chatzi L, Knudsen LE, Anna L, Ketzel M, Haugen M, Botsivali M, Nieuwenhuijsen MJ, Cirach M, Toledano MB, Smith RB, Fleming S, Agramunt S, Kyrtopoulos SA, LukĂĄcs V, Kleinjans JC, SegerbĂ€ck D, Kogevinas M. 2015. Environmental, dietary, maternal, and fetal predictors of bulky DNA adducts in cord blood: a European motherâchild study (NewGeneris). Environ Health Perspect 123:374â380;âhttp://dx.doi.org/10.1289/ehp.140861
Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: The NewGeneris cohort
Background: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUXŸ (chemically activated luciferase expression for androgens) (8 genes), ERα CALUXŸ (for estrogens) (2 genes), and DR CALUXŸ (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research
A pilot study of the prognostic significance of metabolic tumor size measurements in PET/CT imaging of lymphomas
This study explores changes in metabolic tumor volume, metabolic tumor
diameter, and maximum standardized uptake value (SUVmax), for earlier
and more accurate identification of lymphomasâ response to treatment
using F-18-FDG PET/CT. Pre-and post-treatment PET/CT studies of 20
patients with Hodgkin disease (HL) and 7 patients with non-Hodgkin
lymphoma (NHL) were retrospectively selected for this study. The
diameter and volume of the metabolic tumor was determined by an in-house
developed adaptive local thresholding technique based on a 50%
threshold of the maximum pixel value within a region. Statistical
analysis aimed at exploring associations between metabolic size
measurements and SUVmax and the ability of the three biomarkers to
predict the patientsâ response to treatment as defined by the four
classes in the European Organization for Research and Treatment of
Cancer (EORTC) guidelines. Results indicated moderate correlations
between % change in metabolic tumor volume and % change in metabolic
tumor maximum diameter (R=0.51) and between % change in maximum
diameter and % change in SUVmax (R=0.52). The correlation between %
change in tumor volume and % change in SUVmax was weak (R=0.24). The %
change in metabolic tumor size, either volume or diameter, was a âvery
strongâ predictor of response to treatment (R=0.89), stronger than
SUVmax (R=0.63). In conclusion, metabolic tumor volume could have
important prognostic value, possibly higher than maximum metabolic
diameter or SUVmax that are currently the standard of practice. Volume
measurements, however, should be based on robust and standardized
segmentation methodologies to avoid variability. In addition, SUV-peak
or lean body mass corrected SUV-peak may be a better PET biomarker than
SUVmax when SUV-volume combinations are considered
Additional file 1: Tables S1ĂąÂÂS5 of Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study
with additional results can be found in the Additional file documents; RKelly_Additional_files.docx. (DOCX 72 kb
Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)
PCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development
Tea and coffee consumption in relation to DNA methylation in four European cohorts
Lifestyle factors, such as food choices and exposure to chemicals, can alter DNAmethylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea have been suggested to play an important role inmodulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogenmetabolism. Thesemechanismsmay bemediated by changes in DNA methylation. To investigate if DNAmethylation in blood is associated with coffee and tea consumption, we performed a genome-wide DNAmethylation study for coffee and tea consumption in four European cohorts (N=3,096). DNAmethylation wasmeasured fromwhole blood at 421,695 CpG sites distributed throughout the genome and analysed inmen and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed. After adjusting formultiple testing, themeta-analysis revealed that two individual CpG-sites,mapping to DNAJC16 and TTC17, were differentiallymethylated in relation to tea consumption in women. No individual sites were associated withmen or with the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentiallymethylated in relation to tea consumption in women. These regions contained genes known to interact with estradiolmetabolismand cancer. No significant regions were found in the sex-combined andmale-only analysis for either tea or coffee consumption.</p