Kidney Cancer Risk Associated with Historic Groundwater Trichloroethylene Contamination

Trichloroethylene (TCE) is a well-documented kidney carcinogen based on a substantial body of evidence including mechanistic and animal studies, as well as reports from occupational settings. However, the cancer risks for those in residential exposures such as TCE contamination in groundwater are much less clear. The objective of this study was to perform a detailed spatio-temporal analysis of estimated residential TCE exposure in New Hampshire, US. We identified kidney cancer cases (n = 292) and age-, gender-matched controls (n = 448) from the Dartmouth-Hitchcock Health System and queried a commercial financial database for address histories. We used publically available data on TCE levels in groundwater measured at contaminated sites in New Hampshire and then modeled the spatial dispersion and temporal decay. We overlaid geospatial residential locations of cases and controls with yearly maps of estimated TCE levels to estimate median exposures over the 5, 10, and 15-year epochs before diagnosis. The 50th–75th percentile of estimated residential exposure over a 15-year period was associated with increased kidney cancer risk (adjusted Odds Ratio (OR) 1.78 95% CI 1.05–3.03), compared to <50th percentile. This finding supports the need for groundwater monitoring of TCE contaminated sites to identify potential public health risks.

Health risks of adults in Hong Kong related to inhalation of particle-bound heavy metal(loid)s

Heterogeneity between ambient and personal exposure to heavy metals has been documented. However, few studies have investigated potential health risks posed by inhalational exposure to airborne heavy metal(loid)s at the individual level. A total of 404 personal fine particles (PM2.5) samples were collected from 61 adult residents (aged 18–63 years) in Hong Kong during 2014–2015. Heavy metal(loid)s were analyzed using energy dispersive X-ray fluorescence. Among the analyzed heavy metal(loid)s, zinc (Zn) was the most abundant component in personal PM2.5, followed by lead (Pb), copper (Cu), and vanadium (V); cobalt (Co) and cadmium (Cd) were not detectable. Health risks of personal exposure to heavy metal(loid)s via inhalation were assessed for adults, including non-cancer risks that were characterized by hazard quotient (HQ) and hazard index (HI). The results indicated that non-cancer risks of heavy metal(loid)s were attributable to Cu, with a 95th HQ value > 1. Arsenic (As) and hexavalent chromium [Cr (VI)] were also significant contributors to inhalation cancer risks (> 1 × 10−6) for the adult participants. Finally, we employed a Monte Carlo simulation to evaluate the uncertainty associated with health risk assessment. The mean and median upper-bound lifetime cancer risk associated with inhalation exposure to carcinogenic heavy metal(loid)s exceeded the acceptable level (1 × 10−6) for adults. Traffic emission (including non-tailpipe exhaust), shipping emission, and regional pollution were significant sources of heavy metals. These findings suggest that emission controls targeting local vehicles and vessels should be given priority in Hong Kong.

USE OF MICRONUCLEUS EXPERIMENTS FOR THE DETECTION OF HUMAN CANCER RISKS: A BRIEF OVERVIEW

Introduction. Micronuclei (MN) are small extranuclear DNA-containing structures that are formed as a consequence of structural and numerical chromosomal aberrations. The advantage of MN experiments compared to conventional chromosomal analyses in metaphase cells is that the scoring is by far less time consuming and laborious. MN experiments are currently widely used for the routine screening of chemicals in vitro and in vivo but also for environmental control and human biomonitoring Objectives. The purpose of this review was to collect data on the use of MN experiments for the detection of increased cancer risks as a consequence of environmental, lifestyle and occupational exposures and the detection/diagnosis of different forms of cancer. Methods. Analysis of the literature on methods for MN experiments with humans; as well as the use of this technique in different areas of research. Results. To date, a wide range of protocols for human biomonitoring studies has been developed for the measurement of MN formation in peripheral blood cells and in epithelial from different organs (buccal and nasal cavity, cervix and bladder). In addition to MN, other nuclear anomalies can be scored which reflect genetic instability as well as acute toxicity and the division of target cells. Conclusions. The evidence is accumulating that MN can be used as a diagnostic tool for the detection of increased cancer risks as well as for the early diagnosis of cervical and bladder cancer

Ageing-related markers and risks of cancer and cardiovascular disease: a prospective study in the EPIC-Heidelberg cohort

Biological age is an important risk factor for chronic diseases. We examined the associations between five markers of unhealthy ageing; Growth Differentiation Factor-15 (GDF-15), N-terminal pro-brain natriuretic peptide (NT-proBNP), glycated hemoglobin A1c (HbA1C), C-Reactive Protein (CRP) and cystatin-C; with risks of cancer and cardiovascular disease (CVD). We used a case-cohort design embedded in the EPIC-Heidelberg cohort, including a subcohort of 3792 participants along with 4867 incident cases of cancer and CVD. Hazard ratios (HRs) were computed and the strongest associations were used to build weighted multi-marker combinations, and their associations with cancer and CVD risks were tested. After adjusting for common confounders, we observed direct associations of GDF-15 with lung cancer risk, NT-proBNP with breast, prostate and colorectal cancers, HbA1C with lung, colorectal, and breast cancer risks, and CRP with lung and colorectal cancer risks. An inverse association was observed for GDF-15 and prostate cancer risk. We also found direct associations of all 5 markers with myocardial infarction (MI) risk, and of GDF-15, NT-proBNP, CRP and cystatin-C with stroke risk. A combination of the independently-associated markers showed a moderately strong association with the risks of cancer and CVD (HRQ4-Q1 ranged from 1.78[1.36, 2.34] for breast cancer, when combining NT-proBNP and HbA1C, to 2.87[2.15, 3.83] for MI when combining NT-proBNP, HbA1C, CRP and cystatin-C). This analysis suggests that combinations of biomarkers related to unhealthy ageing show strong associations with cancer risk, and corroborates published evidence on CVD risk. If confirmed in other studies, using these biomarkers could be useful for the identification of individuals at higher risk of age-related diseases.

Exposure and risk characterizations of ochratoxins A and aflatoxins through maize (Zea mays) consumed in different agro-ecological zones of Ghana

Mycotoxin contamination of foodstuffs is a serious food safety concern globally as the prolonged ingestion of these toxins has the tendency to worsen the risk of hepatocellular carcinoma. This study aimed at estimating ochratoxin A (OTA) and aflatoxin (AF) levels above international (European Food Safety Authority, EFSA) and local (Ghana Standards Authority, GSA) standards as well as the health risks associated with the consumption of maize (n = 180) sampled from six (6) regions representing the agro-ecological zones of Ghana. OTA and AF were measured with High-Performance Liquid Chromatography with a Fluorescence detector. Out of the 180 samples analyzed for total aflatoxins (AFtotal), 131/180 tested positive and 127 (70.50%) exceeded the limits of EFSA and ranged 4.27–441.02 µg/kg. While for GSA, 116 (64.44%) of samples exceeded this limit and ranged between 10.18 and 441.02 µg/kg. For OTA, 103/180 tested positive and 94 (52.22%) of samples between the range 4.00–97.51 µg/kg exceeded the tolerable limit of EFSA, whereas 89 (49.44%) and were in the range of 3.30–97.51 µg/kg exceeded the limits of GSA. Risk assessment values for total aflatoxins (AFtotal) ranged between 50 and 1150 ng/kg bw/day, 0.4–6.67, 0–0.0323 aflatoxins ng/kg bw/day and 1.62–37.15 cases/100,000 person/year for Estimated Daily Intake (EDI), Margin of Exposure (MOE), Average Potency, and Cancer Risks respectively. Likewise, ochratoxin (OTA) values were in the ranges of 8.6 × 10–3–450 ng/kg bw/day, 0.05–2059.97, 0–0.0323 ochratoxins ng/kg bw/day and 2.78 × 10–4–14.54 cases/100,000 person/year. Consumption of maize posed adverse health effects in all age categories of the locations studied since the calculated MOE values were less than 10,000.

Investigations concerning the impact of consumption of hot beverages on acute cytotoxic and genotoxic effects in oral mucosa cells

Consumption of very hot beverages and foods increases the incidence of oral and esophageal cancer but the mechanisms are not known and the critical temperature is not well defined. We realized a study with exfoliated cells from the oral cavity of individuals (n = 73) that live in an area in Iran which has the highest incidence of EC worldwide. Consumption of beverages at very high temperatures is a characteristic feature of this population. We analyzed biomarkers which are (i) indicative for genetic instability (micronuclei that are formed as a consequence of chromosomal damage, nuclear buds which are a consequence of gene amplifications and binucleated cells which reflect mitotic disturbances), (ii) markers that reflect cytotoxic effects (condensed chromatin, karyorrhectic, karyolitic and pyknotic cells), (iii) furthermore, we determined the number of basal cells which is indicative for the regenerative capacity of the buccal mucosa. The impact of the drinking temperature on the frequencies of these parameters was monitored with thermometers. We found no evidence for induction of genetic damage but an increase of the cytotoxic effects with the temperature was evident. This effect was paralleled by an increase of the cell division rate of the mucosa which was observed when the temperature exceeded 60 °C. Our findings indicate that cancer in the upper digestive tract in drinkers of very hot beverages is not caused by damage of the genetic material but by an increase of the cell division rate as a consequence of cytotoxic effects which take place at temperatures over 60 °C. It is known from earlier experiments with rodents that increased cell divisions lead to tumor promotion in the esophagus. Our findings provide a mechanistic explanation and indicate that increased cancer risks can be expected when the drinking temperature of beverages exceeds 60 °C.