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Timing of Toenail Collection and Concentrations of Metals in Pancreatic Cancer. Evidence Against Disease Progression Bias.

ABSTRACT: Trace elements such as cadmium, arsenic, zinc or selenium increase or decrease risk of a wide range of human diseases. Their levels in toenails may provide a measure of mid-term intake of trace elements for studies in humans. However, in biologically and clinically aggressive diseases as pancreatic cancer, the progression of the disease could modify such concentrations and produce reverse causation bias. The aim was to analyze the influence of specific time intervals between several clinical events and the collection of toenails upon concentrations of trace elements in patients with pancreatic cancer. Subjects were 118 incident cases of pancreatic adenocarcinoma prospectively recruited in eastern Spain. Toenails were collected at cancer diagnosis, and soon thereafter interviews were conducted. Information on cancer signs and symptoms was obtained from medical records and patient interviews. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. General linear models adjusting for potential confounders were applied to analyze relations between log concentrations of trace elements and the time intervals, including the interval from first symptom of cancer to toenail collection (iST). Toenail concentrations of the 12 trace elements were weakly or not influenced by the progression of the disease or the diagnostic procedures. Concentrations of aluminum were slightly higher in subjects with a longer iST (age, sex and stage adjusted geometric means: 11.44 vs. 7.75 µg/g for iST > 120 days vs. ≤ 40 days). There was a weak inverse relation of iST with concentrations of zinc and selenium (maximum differences of about 20 and 0.08 µg/g, respectively). Conclusions: concentrations of the trace elements were weakly or not influenced by the development of the disease before toenail collection. Only concentrations of aluminum increased slightly with increasing iST, whereas levels of zinc and selenium decreased weakly. Even in an aggressive disease as pancreatic cancer, toenail concentrations of trace elements may provide a valid measure of mid-term intake of trace elements, unaffected by clinical events and disease progression.

Supplementary information

The online version contains supplementary material available at 10.1007/s12403-021-00436-2.

SUBMITTER: Pumarega J

PROVIDER: S-EPMC8533671 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEnvironmental metal exposures have been associated with multiple deleterious health endpoints. DNA methylation (DNAm) may provide insight into the mechanisms underlying these relationships. Toenail metals are non-invasive biomarkers, reflecting a medium-term time exposure window.ObjectivesThis study examined variation in leukocyte DNAm and toenail arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg) among elderly men in the Normative Aging Study, a longitudinal cohort.MethodsWe repeatedly collected samples of blood and toenail clippings. We measured DNAm in leukocytes with the Illumina HumanMethylation450 K BeadChip. We first performed median regression to evaluate the effects of each individual toenail metal on DNAm at three levels: individual cytosine-phosphate-guanine (CpG) sites, regions, and pathways. Then, we applied a Bayesian kernel machine regression (BKMR) to assess the joint and individual effects of metal mixtures on DNAm. Significant CpGs were identified using a multiple testing correction based on the independent degrees of freedom approach for correlated outcomes. The approach considers the effective degrees of freedom in the DNAm data using the principal components that explain >95% variation of the data.ResultsWe included 564 subjects (754 visits) between 1999 and 2013. The numbers of significantly differentially methylated CpG sites, regions, and pathways varied by metals. For example, we found six significant pathways for As, three for Cd, and one for Mn. The As-associated pathways were associated with cancer (e.g., skin cancer) and cardiovascular disease, whereas the Cd-associated pathways were related to lung cancer. Metal mixtures were also associated with 47 significant CpG sites, as well as pathways, mainly related to cancer and cardiovascular disease.ConclusionsThis study provides an approach to understanding the potential epigenetic mechanisms underlying observed relations between toenail metals and adverse health endpoints.

Project description:BackgroundLimited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest.MethodsAssociations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations <1 ?g/L versus ?1 ?g/L.ResultsAs expected, toenail arsenic concentrations increased with household water arsenic concentrations. Among the foods known to be high in arsenic, no clear relationship between toenail arsenic and rice consumption was detected, but there was a positive association with consumption of dark meat fish, a category that includes tuna steaks, mackerel, salmon, sardines, bluefish, and swordfish. Positive associations between toenail arsenic and consumption of white wine, beer, and Brussels sprouts were also observed; these and most other associations were not modified by exposure via water. However, consumption of two foods cooked in water, beans/lentils and cooked oatmeal, was more strongly related to toenail arsenic among those with arsenic-containing drinking water (?1 ?g/L).ConclusionsThis study suggests that diet can be an important contributor to total arsenic exposure in U.S. populations regardless of arsenic concentrations in drinking water. Thus, dietary exposure to arsenic in the US warrants consideration as a potential health risk.

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Timing of Toenail Collection and Concentrations of Metals in Pancreatic Cancer. Evidence Against Disease Progression Bias.

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