The association between serum copper and anaemia in the adult Second National Health and Nutrition Examination Survey (NHANES II) population

Though common in older adults, anaemia is unexplained in about one-third of cases. As a rare cause of anaemia and neutropenia, Cu deficiency could account for some cases of unexplained anaemia. We examined the relationship between serum Cu and unexplained anaemia among 11 240 participants in the Second National Health and Nutrition Examination Survey (NHANES II): 638 (5.7 % of all adults) were anaemic; 421 (3.7 %) were not explained by deficiencies of vitamin B12, folate or Fe, chronic illness or renal disease. Spline regression showed a U-shaped relationship between serum Cu levels and unexplained anaemia, indicating that both high and low serum Cu levels are associated with unexplained anaemia in adults. Chronic inflammation and mild Fe deficiency could account for the association between unexplained anaemia and elevated Cu levels. On the other hand, the finding of hypocupraemia in a subset of adults with unexplained anaemia suggests that Cu deficiency may be a common reversible cause of anaemia in adults

Initial Assessment of Variability of Responses to Toxicants in Donor-Specific Endothelial Colony Forming Cells

There is increased interest in using high throughput in vitro assays to characterize human population variability in response to toxicants and drugs. Utilizing primary human endothelial colony-forming cells (ECFCs) isolated from blood would be highly useful for this purpose because these cells are involved in neonatal and adult vasculogenesis. We characterized the cytotoxicity of four known toxic chemicals (NaAsO2, CdCl2, tributyltin [TBT], and menadione) and their four relatively nontoxic counterparts (Na2HAsO4, ZnCl2, SnCl2, and phytonadione, respectively) in eight ECFC clones representing four neonatal donors (2 male and 2 female donors, 2 clones per donor). ECFCs were exposed to 9 concentrations of each chemical in duplicate; cell viability was evaluated 48 h later using the fluorescent vital dye fluorescent dye 5-Carboxyfluorescein Diacetate (CFDA), yielding concentration-effect curves from each experiment. Technical (day-to-day) variability of the assay, assessed from three independent experiments, was low: p-values for the differences of results were 0.74 and 0.64 for the comparison of day 2 vs. day 1 and day 3 vs. day 1, respectively. The statistical analysis used to compare the entire concentration-effect curves has revealed significant differences in levels of cytotoxicity induced by the toxic and relatively nontoxic chemical counterparts, demonstrating that donor-specific ECFCs can clearly differentiate between these two groups of chemicals. Partitioning of the total variance in the nested design assessed the contributions of between-clone and between-donor variability for different levels of cytotoxicity. Individual ECFC clones demonstrated highly reproducible responses to the chemicals. The most toxic chemical was TBT, followed by NaAsO2, CdCl2, and Menadione. Nontoxic counterparts exhibited low cytotoxicity at the higher end of concentration ranges tested. Low variability was observed between ECFC clones obtained from the same donor or different donors for CdCl2, NaAsO2, and TBT, but for menadione, the between-donor variability was much greater than the between-clone variability. The low between-clone variability indicates that an ECFC clone may represent an individual donor in cell-based assays, although this finding must be confirmed using a larger number of donors. Such confirmation would demonstrate that an in vitro ECFC-based testing platform can be used to characterize the inter-individual variability of neonatal ECFCs exposed to drugs and/or environmental toxicants

Human Exposure to Selected Animal Neurocarcinogens: A Biomarker-Based Assessment and Implications for Brain Tumor Epidemiology

This review is based on the proceedings from the Second Lebow Conference held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the 4 most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types

Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma

<p>Abstract</p> <p>Background</p> <p>Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis.</p> <p>Methods</p> <p>Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects.</p> <p>Results</p> <p>Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n = 748) to self-reported cases only (n = 450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases.</p> <p>Conclusions</p> <p>The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.</p

Exploring the association between melanoma and glioma risks

PurposeGliomas are one of the most fatal malignancies, with largely unknown etiology. This study examines a possible connection between glioma and melanoma, which might provide insight into gliomas' etiology.MethodsUsing data provided by the Surveillance, Epidemiology, and End Results program from 1992 to 2009, a cohort was constructed to determine the incidence rates of glioma among those who had a prior diagnosis of invasive melanoma. Glioma rates in those with prior melanoma were compared with those in the general population.ResultsThe incidence rate of all gliomas was greater among melanoma cases than in the general population: 10.46 versus 6.13 cases per 100,000 person-years, standardized incidence ratios&nbsp;=&nbsp;1.42 (1.22-1.62). The female excess rate was slightly greater (42%) than that among males (29%). Sensitivity analyses did not reveal evidence that radiation treatment of melanoma is responsible for the detected gap in the rates of gliomas.ConclusionsOur analysis documented increased risk of glioma among melanoma patients. Because no common environmental risk factors are identified for glioma and melanoma, it is hypothesized that a common genetic predisposition may be responsible for the detected association

A pooled multisite analysis of the effects of atopic medical conditions in glioma risk in different ethnic groups

PurposeThe incidences of atopic conditions (allergies, asthma, or eczema) and glioma vary by ethnicity. Atopic conditions are inversely associated with gliomas. We conducted a pooled multisite study investigating the associations of atopic conditions with glioma in different race/ethnicity groups.MethodsUsing glioma cases and healthy controls, unconditional logistic regression was conducted to assess the associations of atopic conditions with glioma separately in white, black, Asian, and Hispanic subpopulations. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsGlioblastoma multiforme cases were less likely than controls to report a history of atopic conditions in whites (OR = 0.46, [95% CI, 0.38-0.54]) and Asians (OR = 0.27, [95% CI, 0.10-0.73]). The same trend was seen when looking at glioma cases of all histologies. An inverse association was not seen in blacks for glioblastoma multiforme or all histologies combined.ConclusionsThe inverse association between glioma and atopic conditions may vary by ethnicity due to a difference in the biology of atopic conditions in different ethnicities but may be due to chance because of the limitations of small nonwhite sample sizes