Suchergebnisse

Background: Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary. Objectives: To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Methods: MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects' residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders. Results: Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44–2.87) to 3 km (1.26; 1.00–1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77–4.00), surface treatment of metals (1.48; 1.08–2.02), glass and mineral fibers (2.06; 1.39–3.07), organic chemical industry (4.80; 3.20–7.20), inorganic chemical industry (6.74; 4.38–10.36), food/beverage sector (3.34; 2.38–4.68), and surface treatment using organic solvents (6.16; 4.06–9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91–14.28), antimony (5.30; 3.45–8.15), naphthalene (3.11; 2.16–4.49), organotin compounds (2.64; 1.76–3.98), manganese (2.53; 1.63–3.93), dichloromethane (2.52; 1.74–3.66), and vanadium (2.49; 1.59–3.91). Conclusions: Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer. ; Scientific Foundation of the Spanish Association Against Cancer (Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC)) EVP-1178/14 ; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) ; Instituto de Salud Carlos III FIS 12/01416 ; Carlos III Institute of Health (ISCIII) grants ; ERDF funds-a way to build Europe PI08/0533 PI08/1359 PI08/1770 PS09/00773Cantabria PS09/01286-Leon PS09/01662-Granada PS09/01903Valencia PS09/02078-Huelva PI11/00226 PI11/01403 PI11/01810 PI11/01889-FEDER PI11/02213 PI12/00150 PI12/00265 ; Fundacion Caja de Ahorros de Asturias ; University of Oviedo ; Junta de Castilla y Leon LE22A10-2 ; Regional Government of the Basque Country ; Conselleria de Sanitat of the Generalitat Valenciana AP_061/10 ; Junta de Andalucia PI-0571-2009 PI-0306-2011 salud201200057018tra ; Catalan Government DURSI grant 2014SGR647 ; European Commission European Commission Joint Research Centre FOOD-CT-2006036224-HIWATE ; La Caixa Foundation 2010ACUP 00310 ; Agency for Management of University and Research Grants (AGAUR) of the Catalan Government 2017SGR723 ; Spanish Association Against Cancer (AECC) Scientific Foundation ; The ERDF funds-a way to build Europe PI12/00488 PI12/00715 PI12/01270 PI14/00613 PI14/01219 PI15/00069 PI15/00914 PI15/01032 PI17-00092

Background: Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary. Objectives: To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Methods: MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects' residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders. Results: Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44-2.87) to 3 km (1.26; 1.00-1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77-4.00), surface treatment of metals (1.48; 1.08-2.02), glass and mineral fibers (2.06; 1.39-3.07), organic chemical industry (4.80; 3.20-7.20), inorganic chemical industry (6.74; 4.38-10.36), food/beverage sector (3.34; 2.38-4.68), and surface treatment using organic solvents (6.16; 4.06-9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91-14.28), antimony (5.30; 3.45-8.15), naphthalene (3.11; 2.16-4.49), organotin compounds (2.64; 1.76-3.98), manganese (2.53; 1.63-3.93), dichloromethane (2.52; 1.74-3.66), and vanadium (2.49; 1.59-3.91). Conclusions: Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer. ; This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) – EVP-1178/14); Spain's Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416); Carlos III Institute of Health (ISCIII) grants, cofunded by ERDF funds–a way to build Europe– (grants PI08/0533, PI08/1359, PI08/1770, PS09/00773-Cantabria, PS09/01286-Leon, PS09/01662-Granada, PS09/01903-Valencia, PS09/02078-Huelva, PI11/00226, PI11/01403, PI11/01810, PI11/01889-FEDER, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI14/01219, PI15/00069, PI15/00914, PI15/01032, PI17-00092); the Fundación Marqués de Valdecilla (API 10/09); the Junta de Castilla y León (LE22A10-2); the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); the Catalan Government DURSI grant 2014SGR647; the European Commission grants FOOD-CT-2006-036224-HIWATE; the Recercaixa (2010ACUP 00310); Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723

Background A total of 2,514,346 metric tons (Mt) of asbestos were imported into Spain from 1906 until the ban on asbestos in 2002. Our objective was to study pleural cancer mortality trends as an indicator of mesothelioma mortality and update mortality predictions for the periods 2011–2015 and 2016–2020 in Spain. ; Methods Log-linear Poisson models were fitted to study the effect of age, period of death and birth cohort (APC) on mortality trends. Change points in cohort- and period-effect curvatures were assessed using segmented regression. Fractional power-link APC models were used to predict mortality until 2020. In addition, an alternative model based on national asbestos consumption figures was also used to perform long-term predictions. ; Results Pleural cancer deaths increased across the study period, rising from 491 in 1976–1980 to 1,249 in 2006–2010. Predictions for the five-year period 2016–2020 indicated a total of 1,319 pleural cancer deaths (264 deaths/year). Forecasts up to 2020 indicated that this increase would continue, though the age-adjusted rates showed a levelling-off in male mortality from 2001 to 2005, corresponding to the lower risk in post-1960 generations. Among women, rates were lower and the mortality trend was also different, indicating that occupational exposure was possibly the single factor having most influence on pleural cancer mortality. ; Conclusion The cancer mortality-related consequences of human exposure to asbestos are set to persist and remain in evidence until the last surviving members of the exposed cohorts have disappeared. It can thus be assumed that occupationally-related deaths due to pleural mesothelioma will continue to occur in Spain until at least 2040. ; The study was partially supported by a research grant from the Spanish Health Research Fund (FIS PI11/00871) and the HAR2009-07543 project of the Ministry of Science and Innovation. The Department of Labour of the Government of Catalonia provided the asbestos consumption data.

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions from primary human lung tissues (HLT), we have developed a platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. We show that the HLT model preserves its main cell populations, maintains the expression of proteins required for SARS-CoV-2 infection, and identifies alveolar type II (AT-II) cells as the most susceptible cell targets for SARS-CoV-2 in the human lung. Antiviral testing of 39 drug candidates revealed a highly reproducible system, and provided the identification of new compounds missed by conventional systems such as VeroE6. Using this model, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a novel and relevant physiological model for the study of SARS-CoV-2. ; This work was primarily supported by a grant from the Health Department of the Government of Catalonia (DGRIS 1_5). This work was additionally supported in part by the Spanish Health Institute Carlos III (ISCIII, PI17/01470), the Spanish Secretariat of Science and Innovation and FEDER funds (grant RTI2018-101082-B-I00 [MINECO/FEDER]), the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA (RD16/0025/0007), the European Regional Development Fund (ERDF), the Fundació La Marató TV3 (grants 201805-10FMTV3 and 201814-10FMTV3), the Gilead fellowships GLD19/00084 and GLD18/00008 and the Becas Taller Argal 2020. M.J.B is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). N.M. is supported by a Ph.D. fellowship from the Vall d'Hebron Institut de Recerca (VHIR). The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript. ; No

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2. ; This work was primarily supported by a grant from the Health Department of the Government of Catalonia (DGRIS 1_5) to M.G and MJ.B. This work was additionally supported in part by the Spanish Health Institute Carlos III (ISCIII, PI17/01470 to M.G; PI19CIII/00004 to J.A; PI21CIII/00025 to J.G-P and COV20-00679 (MPY 222-20) to J.G-P), the Spanish Secretariat of Science and Innovation and FEDER funds (grant RTI2018-101082-B-I00 [MINECO/FEDER]) to MJ.B, the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA and the European Regional Development Fund (ERDF) (RD16/0025/0007 to MJ.B and RD16CIII/0002/0001 to J.A), the Fundació La Marató TV3 (grants 201805-10FMTV3 and 202104FMTV3 to MJ.B; 201814-10FMTV3 and 202112FMTV3 to M.G), the Gilead fellowships GLD19/00084 to M.G and GLD18/00008 to MJ.B and the Becas Taller Argal 2020 to MJ.B. Salary for MJ.B is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). N.M and D.P are supported by a Ph.D. fellowship from the Vall d'Hebron Institut de Recerca (VHIR).The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript. ; Peer reviewed

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2. ; This work was primarily supported by a grant from the Health Department of the Government of Catalonia (DGRIS 1_5). This work was additionally supported in part by the Spanish Health Institute Carlos III (ISCIII, PI17/01470; PI19CIII/00004; PI21CIII/00025 and COV20-00679 (MPY 222-20)), the Spanish Secretariat of Science and Innovation and FEDER funds (grant RTI2018-101082-B-I00 [MINECO/FEDER]), the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA (RD16/0025/0007 and RD16CIII/0002/0001), the European Regional Development Fund (ERDF), the Fundació La Marató TV3 (grants 201805-10FMTV3 and 201814- 10FMTV3), the Gilead fellowships GLD19/00084 and GLD18/00008 and the Becas Taller Argal 2020. M.J.B is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). N.M. is supported by a Ph.D. fellowship from the Vall d'Hebron Institut de Recerca (VHIR). The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript. ; No

BACKGROUND: Night shift work, exposure to light at night (ALAN) and circadian disruption may increase the risk of hormone-dependent cancers. OBJECTIVES: We evaluated the association of exposure to ALAN during sleeping time with breast and prostate cancer in a population based multicase-control study (MCC-Spain), among subjects who had never worked at night. We evaluated chronotype, a characteristic that may relate to adaptation to light at night. METHODS: We enrolled 1,219 breast cancer cases, 1,385 female controls, 623 prostate cancer cases, and 879 male controls from 11 Spanish regions in 2008-2013. Indoor ALAN information was obtained through questionnaires. Outdoor ALAN was analyzed using images from the International Space Station (ISS) available for Barcelona and Madrid for 2012-2013, including data of remotely sensed upward light intensity and blue light spectrum information for each geocoded longest residence of each MCC-Spain subject. RESULTS: Among Barcelona and Madrid participants with information on both indoor and outdoor ALAN, exposure to outdoor ALAN in the blue light spectrum was associated with breast cancer [adjusted odds ratio (OR) for highest vs. lowest tertile, OR=1.47; 95% CI: 1.00, 2.17] and prostate cancer (OR=2.05; 95% CI: 1.38, 3.03). In contrast, those exposed to the highest versus lowest intensity of outdoor ALAN were more likely to be controls than cases, particularly for prostate cancer. Compared with those who reported sleeping in total darkness, men who slept in "quite illuminated" bedrooms had a higher risk of prostate cancer (OR=2.79; 95% CI: 1.55, 5.04), whereas women had a slightly lower risk of breast cancer (OR=0.77; 95% CI: 0.39, 1.51). CONCLUSION: Both prostate and breast cancer were associated with high estimated exposure to outdoor ALAN in the blue-enriched light spectrum. https://doi.org/10.1289/EHP1837. ; The study was partially funded by the Accion Transversal del Cancer, approved by the Spanish Ministry Council on 11 October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01889-FEDER, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI14/0613), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL [the ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)], by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government–Agency for Management of University and Research Grants (AGAUR) grants 2014SGR647 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias, and by the University of Oviedo. ISGlobal is a member of the Centres de Recerca de Catalunya (CERCA) Programme, Generalitat de Catalunya. This research was also supported in part by the STARS4ALL project funded by the H2020-ICT-2015-688135 program of the European Union, the ORISON project funded by the H2020-INFRASUPP-2015-2 program of the European Union, and through the resources of researchers and collaborators of the Cities at Night project. J.G.-P. was funded by the Scientific Foundation of the Spanish Association against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC), EVP-1178/14).

Background: Self-reported data about environmental exposures can lead to measurement error. Objectives: To validate the self-reported perception of proximity to industrial facilities. Methods: MCC-Spain is a population-based multicase-control study of cancer in Spain that recruited incident cases of breast, colorectal, prostate, and stomach cancer. The participant's current residence and the location of the industries were geocoded, and the linear distance between them was calculated (gold standard). The epidemiological questionnaire included a question to determine whether the participants perceived the presence of any industry at ≤1 km from their residences. Sensitivity and specificity of individuals' perception of proximity to industries were estimated as measures of classification accuracy, and the area under the curve (AUC) and adjusted odds ratios (aORs) of misclassification were calculated as measures of discrimination. Analyses were performed for all cases and controls, and by tumor location, educational level, sex, industrial sector, and length of residence. Finally, aORs of cancer associated with real and self-reported distances were calculated to explore differences in the estimation of risk between these measures. Results: Sensitivity of the questionnaire was limited (0.48) whereas specificity was excellent (0.89). AUC was sufficient (0.68). Participants with breast (aOR(95%CI)=2.03 (1.67;2.46)), colorectal (aOR(95%CI)=1.41 (1.20;1.64)) and stomach (aOR(95%CI)=1.59 (1.20;2.10)) cancer showed higher risk of misclassification than controls. This risk was higher for lower educational levels (aOR 15 years (95%CI)=0.56 (0.36;0.85)). The use of selfreported proximity vs. real distance to industrial facilities biased the effect on cancer risk towards the nullity. Conclusions: Self-reported distance to industrial facilities can be a useful tool for hypothesis generation, but hypothesis-testing studies should use real distance to report valid conclusions. The sensitivity of the question might be improved with a more specific formulation ; This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) – EVP-1178/14), Spain's Health Research Fund (Fondo de Investigación Sanitaria – FIS 12/01416), the Spanish Ministry of Economy and Competitiveness (Carlos III Institute of Health; PI12/00488, PI12/00265, PI12/01270, PI12/ 00715, PI12/00150, PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI14/01219 and Río Hortega CM13/00232), the Catalan Government 2009SGR1489 & 2014SGR756-F, the Fundación Marqués de Valdecilla (API 10/09), the ICGC International Cancer Genome Consortium CLL, the Junta de Castilla y León (LE22A10-2), the Consejería de Salud of the Junta de Andalucía (PI-0571), the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), the Recercaixa (2010ACUP 310), and the Regional Government of the Basque Country by European Commission grants FOOD-CT-2006-036224-HIWATE