Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort.

BACKGROUND: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy. METHODS: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models. RESULTS: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (ß 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele). CONCLUSIONS: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations.

Serum levels of PCDDs, PCDFs and dl-PCBs in general population residing far and near from an urban waste treatment plant under construction in Gipuzkoa, Basque Country (Spain).

This research focused on investigating the basal serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in the general population residing in two urban-industrial zones near and far from an energy recovery plant under construction in Gipuzkoa, Basque Country (Spain). The study used a cross-sectional design and included 227 participants who were randomly selected from municipal censuses in both areas. The participants were stratified based on age (ranging from 18 to 70 years) and sex. Serum samples were collected from the participants and analysed following the established protocol to measure the concentrations of PCDD/Fs and dl-PCBs. The study used multiple linear regression models to assess the impact of various sociodemographic variables, lifestyle factors, reproductive history, and diet on the variability of the measured compounds in the participants' serum. The median total toxicity equivalent (TEQ) in serum, was 10.58 pg WHO-TEQ2005 g-1 lipid. Serum PCDD levels were lower in the population residing in the "far" zone than the "near" zone. Age was positively associated with both PCDD/F and dl-PCB levels, indicating that older participants had higher concentrations of these compounds in their serum. This finding might be attributed to cumulative exposure over time. In terms of sex differences, women exhibited lower levels of dl-PCBs compared to men. Among lifestyle factors, smokers showed lower levels of dl-PCBs compared to non-smokers. Furthermore, daily alcohol consumption was significantly associated with higher serum levels of these compounds, with daily drinkers showing higher levels than non-drinkers. Consumption of local poultry was associated with significantly higher serum levels and oil consumption with low levels of PCDD/Fs.

Characterization of PCDD/F and dl-PCB levels in air in Gipuzkoa (Basque Country, Spain).

This research examines the levels and trends of pollutants, specifically 17 congeners of PCDD/Fs and 12 dl-PCBs, in the air measured in the province of Gipuzkoa (Basque Country, Spain). The study used PCDD/Fs, dl-PCB, and the sum of dioxin-like compounds as separate response variables. A total of 113 air samples were collected and analyzed using the method described in the European Standard (EN-1948:2006) from two industrial areas. The results were analyzed using non-parametric test to assess the variability of these pollutants based on different factors (year, season and day of the week) and General Linear Models to assess the weight of each factor. The study found that the toxic equivalents (TEQs) for PCDD/Fs were 12.29 fg TEQm-3 and for dl-PCBs were 1.63 fg TEQm-3, which were in a similar range or lower than those observed in other national and international studies in industrial areas. The results showed temporal variations, with higher levels of PCDD/Fs in autumn-winter than in spring-summer and higher levels of PCDD/Fs and dl-PCBs during weekdays than on weekends. The industrial area where the energy recovery plant (ERP) will be located had higher levels of air pollutants due to the presence of two PCDD/Fs emitting industries nearby, as indicated by the Spanish Registry of Polluting Emission Sources. Both industrial areas showed similar profiles of PCDD/Fs and dl-PCBs, with the PCDD/F profiles dominated by OCDD, 1,2,3,4,6,7,8-HpCDD, and 1,2,3,4,6,7,8-HpCDF in terms of concentrations and 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF, and 2,3,7,8-TCDD in terms of TEQs. The dl-PCB profiles were dominated by PCB 118, PCB 105, and PCB 77 in terms of concentrations and PCB 126 in terms of TEQs. The findings of this study can serve as an indicator of the potential impact of ERP on the health of the resident population and the environment.

Serum metal levels in a population of Spanish pregnant women.

OBJECTIVE: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. METHOD: Cross-sectional study with 1279 participants from the INMA cohorts. RESULTS: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B6 supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B12 supplementation (p=0.006). CONCLUSIONS: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.

Time trends in serum organochlorine pesticides and polychlorinated biphenyls in the general population of Biscay, Spain.

Despite the measures adopted, levels of organochlorine compounds (OCs) are still being detected in the human body. This study aimed to explore factors related to changes in the concentrations of polychlorinated biphenyls (PCBs) and pesticide OCs in blood samples obtained from a general population cohort. Two cross-sectional samples were taken from 162 adults (2-75 years of age), with a gap of 2 years, from four areas in Biscay (Spain). More than 75 % had quantifiable levels of hexachlorobenzene (HCB), beta-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethylene, and PCBs 138 153 and 180. During this time, significant changes were observed: PCB 180 and HCB levels increased, and PCB 138 and ß-HCH levels decreased. Regarding age, this study shows a decrease suggesting a cohort effect. The period was not related to the decrease of levels in all age intervals, but a statistically significant increase of PCBs in older people was found. High body mass index was associated with lower PCB 180 levels and greater HCH levels. Inversely, greater levels of HCB and ß-HCH were in those who had lost weight before the study. Levels of HCB and ß-HCH were also greater in women who had had children, although they were lower in those who breastfed. Levels of these same OCs were greater in fish consumers, whereas those of PCBs 138 and 153 were greater in those who consumed local produce; all of these trends were close to significance. Efforts should continue to decrease exposure to these pollutants and to assess their influence on general population.

Principales resultados del programa de cribado de cáncer colorrectal en el País Vasco / Main results of the colorectal cancer screening program in the Basque Country (Spain)

Objetivo: Describir la estrategia del Programa de Cribado de Cáncer Colorrectal en el País Vasco y los principales resultados de participación en la primera ronda (2009-2011). Método: Estudio retrospectivo de las invitaciones realizadas en 2009-2011 y comparación de las tasas de participación y positividad de la prueba de sangre oculta en heces por sexo y grupos de edad. Resultados: Se obtuvieron 235.371 invitaciones válidas (personas correctamente localizadas), con una participación media del 64,3% (intervalo de confianza del 95% [IC95%]: 64,1-64,5) y con diferencias significativas (p<0,001) entre mujeres (67,1%; IC95%: 66,9-67,4) y hombres (61,4%; IC95%: 61,1-61,7). El porcentaje de positivos fue superior (p<0,001) en los hombres (9,1%; IC95%: 8,9-9,2) que en las mujeres (4,8%; IC95%: 4,7-4,9). Conclusiones: Las tasas de participación en el programa se consideraron adecuadas en comparación con los estudios revisados. Estas tasas podrían estar relacionadas con la estrategia de invitación y con factores culturales y sociales (AU)

Objective: To describe the procedures of the colorectal cancer screening program in the Basque Country (Spain), and the main results of the first rounds in 2009-2011. Method: We carried out a retrospective study of invitations to attend screening between 2009 and 2011. Participation rates and the number of positive results of the fecal occult blood test (FOBT) were analyzed by sex and age group. Results: There were 235.371 valid invitations (sent to the correct addresses), with an average participation rate of 64.3% (95%CI: 64.1-64.5%). Significant differences were found (p<0,001) between women (67.1%; 95%CI: 66.9-67.4) and men (61.4%; 95%CI: 61.1-61.7). The rate of positive FOBT results was higher (p<0,001) among men (9.1%; 95%CI: 8.9-9.2) than among women (4.8%; 95%CI: 4.7-4.9). Conclusions: Participation rates were adequate compared with those in the reviewed literature. These rates were probably affected by the invitation strategy and by cultural and social factors (AU)

[Main results of the colorectal cancer screening program in the Basque Country (Spain)]. / Principales resultados del programa de cribado de cáncer colorrectal en el País Vasco.

OBJECTIVE: To describe the procedures of the colorectal cancer screening program in the Basque Country (Spain), and the main results of the first rounds in 2009-2011. METHOD: We carried out a retrospective study of invitations to attend screening between 2009 and 2011. Participation rates and the number of positive results of the fecal occult blood test (FOBT) were analyzed by sex and age group. RESULTS: There were 235.371 valid invitations (sent to the correct addresses), with an average participation rate of 64.3% (95%CI: 64.1-64.5%). Significant differences were found (p<0,001) between women (67.1%; 95%CI: 66.9-67.4) and men (61.4%; 95%CI: 61.1-61.7). The rate of positive FOBT results was higher (p<0,001) among men (9.1%; 95%CI: 8.9-9.2) than among women (4.8%; 95%CI: 4.7-4.9). CONCLUSIONS: Participation rates were adequate compared with those in the reviewed literature. These rates were probably affected by the invitation strategy and by cultural and social factors.

Heavy metal levels (Pb, Cd, Cr and Hg) in the adult general population near an urban solid waste incinerator.

In 2005 an urban solid waste incinerator (SWI) was commissioned in Bilbao (Basque Country, Spain). Serum and urine samples were collected from 95 and 107 volunteers in 2006 and 2008 respectively, of which 62 were repeats from the same individuals. Blood lead levels (BPb) were determined, as were the concentrations of cadmium (Cd), chromium (Cr) and mercury (Hg) in urine (UCd, UCr and UHg). The town of Alonsotegi and a borough of Bilbao (Altamira, Rekalde) were considered to be close, less than 2 km from the plant, and correspond to an urban environment with high traffic density. The areas of reference were a borough of Bilbao (Santutxu-Zurbaran), 5 km from the plant, also in an urban area with high traffic density, and a small town with little industrial activity and low traffic density (Balmaseda) 20 km from the plant; neither of these is downwind from the site with respect to prevailing winds. There was a significant correlation for BPb, r=0.63 (p<0.001), between the two surveys. However, there was no linear correlation for the other three metals (UCd, UCr and UHg), between the two sampling periods (p>0.05). Multiple linear regression models did not show increases over time of the levels of BPb, UCd, UCr and UHg in the areas close to the SWI compared to those of areas located further away, after adjusting for confounding variables. These results reinforce the hypothesis that populations near modern plants for solid waste incineration do not manifest increased levels of heavy metals.

[Organochlorine pesticides in the general adult population of Biscay (Spain)]. / Plaguicidas organoclorados en población general adulta de Bizkaia.

OBJECTIVE: To identify and analyze levels of seven organochlorine pesticides [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (ß-HCH), gamma-hexachlorocyclohexane (γ-HCH), heptachlor epoxide, beta-endosulfan, dichlorodiphenyldichloroethylene (p,p'-DDE) and dichlorodiphenyltrichloroethane (p,p'-DDT)] in the serum of adults of four areas of Biscay (Spain) not exposed to known sources of pesticides. METHOD: We analyzed 283 individual samples from volunteers recruited from the census. The volunteers were interviewed using a questionnaire with items on demographic variables and consumption. Data were analyzed using the chi-square test for discrete variables and analysis of variance and multiple linear regression models for continuous variables. RESULTS: We detected p,p'-DDE in 100% of the volunteers (mean: 191.43ng/g lipid), while 31% had detectable levels of p,p'-DDT (mean: 18.9ng/g lipid). Detectable levels of HCB were found in 96.5% of the volunteers (mean: 78.56ng/g lipid), ß-HCH in 90.4% (mean: 42.78ng/g lipid) and γ-HCH in 3.5%. Heptachlor epoxide and beta-endosulfan were not detected. In the regression model higher levels of all pesticides were found with increasing age (p<0.05). There were no significant differences by area of residence, except for HCB and p,p'-DDE. Women had significantly higher levels of HCB and ß-HCH (p<0.001). Body mass index showed a significant positive gradient in HCB and ß-HCH (p<0.05). There was no association between pesticides and other variables, breast feeding, occupation or social class. CONCLUSIONS: These results indicate that the general adult population of Biscay has been and is exposed to organochlorine pesticides. However, their levels are within the range observed by other authors.