Breast cancer risk for the joint exposure to metals and metalloids in women: Results from the EPIC-Spain cohort.

Environmental factors play a role in breast cancer development. While metals and metalloids (MMs) include some carcinogens, their association with breast cancer depends on the element studied. Most studies focus on individual MMs, but the combined effects of metal mixtures remain unclear. The aim of this study was to analyze the relationship between the joint exposure to MMs and the risk of developing female breast cancer. We conducted a case-control study within the multicenter prospective EPIC-Spain cohort. Study population comprised 292 incident cases and 286 controls. Plasma concentrations of 16 MMs were quantified at recruitment. Potential confounders were collected using a questionnaire and anthropometric measurements. Mixed-effects logistic regression models were built to explore the effect of individual MMs. Quantile-based g computation models were applied to identify the main mixture components and to estimate the joint effect of the metal mixture. The geometric means were highest for Cu (845.6 ng/ml) and Zn (604.8 ng/ml). Cases had significantly higher Cu concentrations (p = 0.010) and significantly lower Zn concentrations (p < 0.001). Cu (+0.42) and Mn (+0.13) showed the highest positive weights, whereas Zn (-0.61) and W (-0.16) showed the highest negative weights. The joint effect of the metal mixture was estimated at an OR = 4.51 (95%CI = 2.32-8.79), suggesting a dose-response relationship. No evidence of non-linearity or non-additivity was found. An unfavorable exposure profile, primarily characterized by high Cu and low Zn levels, could lead to a significant increase in the risk of developing female breast cancer. Further studies are warranted to confirm these findings.

Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma.

The management and screening of prostate cancer (PC) is still the main problem in clinical practice. In this study, we investigated the role of aggressiveness genetic markers for PC stratification. We analyzed 201 plasma samples from PC patients and controls by digital PCR. For selection and validation, 26 formalin-fixed paraffin-embedded tissues, 12 fresh tissues, and 24 plasma samples were characterized by RNA-Seq, immunochemistry, immunofluorescence, Western blot, and extracellular-vesicles analyses. We identified three novel non-invasive biomarkers; all with an increased expression pattern in patients (PCA3: p = 0.002, S100A4: p ≤ 0.0001 and MRC2: p = 0.005). S100A4 presents the most informative AUC (area under the curve) (0.735). Combination of S100A4, MRC2, and PCA3 increases the discriminatory power between patients and controls and between different more and less aggressive stages (AUC = 0.761, p ≤ 0.0001). However, although a sensitivity of 97.47% in PCA3 and a specificity of 90.32% in S100A4 was reached, the detection signal level could be variable in some analyses owing to tumor heterogeneity. This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4, MRC2, and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness.

Urinary levels of arsenic and heavy metals in children and adolescents living in the industrialised area of Ria of Huelva (SW Spain).

The Ria of Huelva (south-west Spain) is a highly polluted estuary as a consequence of long-term mining and industrial activities. Between 2003 and 2004, we conducted a biomonitoring study of exposure to arsenic and some heavy metals (cadmium, chromium, copper and nickel) in urine samples of a representative sample (n=227) of children and adolescents residing in this area, and of a reference group of 196 children and adolescents living in other less industrialised areas of Andalusia (south Spain). We also assessed the determinants of the variability in urinary metals within the population of the Ria of Huelva. There were no significant differences in the concentration of metal compounds between the two groups with the exception of Cd levels, which were significantly higher in the reference group. Levels of the five metal ions in both groups were generally within the range of values reported by other biomonitoring studies for general children population, although mean Cd levels tended to be higher as compared to other European studies. Among the population of the Ria of Huelva, the main determinants of the interindividual variation in urinary metals were age, sex, area of residence, and frequency of intake of certain food items (mainly fish and shellfish). Overall, results suggest that living in the Ria of Huelva is not increasing current levels of exposure to certain metals among children and adolescents above those found in other urban areas of Andalusia.

Heavy metal concentrations in the general population of Andalusia, South of Spain: a comparison with the population within the area of influence of Aznalcóllar mine spill (SW Spain).

Levels of metalloids (As - urine) and heavy metals (Hg - urine, Cd - whole blood and Zn - serum) were determined by atomic absorption spectrometry in 601 subjects living in the area affected by the Aznalcóllar mine spill (SW, Spain) and compared with those of a representative sample (960 subjects) selected from the Andalusian community (non-affected area), southern Spain. The characteristic parameters of the analytical method including uncertainty were determined for each metal. Potential associations of metal concentration with age, sex and body mass index as well as life-style habits (smoking, alcohol consumption and food habits) were explored. Concentrations of all the metals studied were statistically higher in the population of the affected area with respect to that of the non-affected area in Andalusia, although levels were always lower or similar to the values reported for the general population and below occupational reference limits. In conclusion, there is a lack of evidence that the spill had any incidence on human health in the population living in the affected area. There are few references in scientific literature reporting values from large series of samples, and hence our data could be useful for further studies.