Yolk sac tumor differentiation in urothelial carcinoma of the urinary bladder: a case report and differential diagnosis

Background: Yolk sac tumor (YST) is a germ cell neoplasm that arises predominantly in the gonads, but can also derive from somatic neoplasms in extragonadal locations. These latter cases have been documented in several organs, although reports from the urinary tract are limited. To our knowledge, this is the first report of a bladder urothelial carcinoma with a predominant component of YST differentiation. Case presentation: We present a unique case of a 76-year-old man with a recurrent urinary bladder tumor, initially interpreted as a high grade urothelial carcinoma with glandular differentiation. In the recurrent tumor, diverse histological patterns were identified, including glandular, hepatoid and sarcomatoid. This tumor showed positivity for AFP, GLP3 and SALL4, and negativity for CK7 and EMA. Fluorescent in situ hybridization study showed a polysomic pattern of chromosome 12. All these findings led to the final diagnosis of a YST derived from urothelial carcinoma. Conclusions: YST differentiation should be considered in the differential diagnosis of a high grade urothelial carcinoma, particularly when glandular and other unusual patterns are observed

Nitrate exposure and cancer risk : evidence from European case-control studies

Ingested nitrate is a precursor of N-nitroso compounds that are carcinogens in animals, with limited evidence in humans. The main objective of this thesis was to evaluate whether the exposure to nitrate through drinking water and diet is associated with carcinogenic effects in humans. This thesis has been conducted in the Centre for Research in Environmental Epidemiology (CREAL) from 2011 to 2015, under the supervision of Cristina M. Villanueva Belmonte PhD. The results of this thesis consists of a compilation of four scientific papers including: a) a descriptive study of nitrate levels in drinking water in Spain (paper I), and b) three large European case-control studies evaluating the risk of prevalent tumors (bladder, breast and colorectal) associated with nitrate exposure through drinking water and diet (papers II, III and IV). This document also includes a general introduction, a description of the methodology, an overall discussion of the results, conclusions and an appendix section.El nitrato ingerido es un precursor de compuestos N-nitroso, que son carcinógenos en animales, con poca evidencia en humanos. El objetivo principal de esta tesis fue evaluar si la exposición a nitrato a través del agua de consumo y la dieta está asociada a efectos carcinogénicos en humanos. Esta tesis fue llevada a cabo en el Centro de Investigación en Epidemiología Ambiental (CREAL) entre 2011 y 2015, bajo la supervisión de Cristina M. Villanueva Belmonte PhD. La parte principal de esta tesis es una compilación de cuatro artículos científicos, que incluyen: a) un estudio descriptivo de los niveles de nitrato en agua de consumo en España (artículo I) y b) tres estudios caso-control que evaluaron el riesgo de tres tumores prevalentes (vejiga, mama y colorrectal), asociados con la exposición a nitrato a través del agua de consumo y la dieta (artículos II, III and IV). Este documento incluye también una introducción general, una descripción de los métodos, una discusión y conclusiones generales y una sección de anexos

Ingested Nitrate and Breast Cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain).

BACKGROUND: Ingested nitrate leads to endogenous formation of N-nitroso compounds that are breast carcinogens in animals, but human evidence is limited. OBJECTIVE: We evaluated ingested nitrate as a risk factor for breast cancer (BC) in a multicase-control study. METHODS: Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008-2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940-2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis. RESULTS: Among the study regions, average ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (≥ 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate. CONCLUSIONS: Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status.This study was funded by the “Acción Transversal del Cáncer del Consejo de Ministros del 11/10/2007” from the “Instituto de Salud Carlos III-FEDER” (PI08/1770, PI08/0533, PI11/00226), ISCIII FIS grants. N.E.H. received financial support for the Ph.D. program from the “Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR FI-DGR 2013) Generalitat de Cataluña.

Colorectal cancer risk and nitrate exposure through drinking water and diet

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.This study was funded by the “Acción Transversal del Cáncer del Consejo de Ministros del 11/10/2007”, from the “Instituto de Salud Carlos III-FEDER” (PI08/1770, PI08/0533, PI11/00226), ISCIII FIS grants, and HIWATE-EU project (036224). NEH receives funding for the PhD program in Biomedicine from the “Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR FI-DGR 2013) Generalitat de Cataluña

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy.

BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. METHODS: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). RESULTS: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations.This work was supported by the Acción Transversal del Cáncer del Consejo de Ministros del 11/10/2007 (M.K. and M.Pollan), from the Instituto de Salud Carlos III-FEDER (M.K.: PI08/1770; C.M.V.: PI08/0533 and PI11/00226) FIS grants and Hiwate EU project (036224), and the Italian Foundation for Research on Cancer (FIRC; C.L.V.)

Nitrate in drinking water and bladder cancer risk in Spain

Background: Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables. Methods: We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview. Results: Average residential levels ranged from 2.1 mg/L to 12.0 mg/L among regions. Adjusted OR (95% CI) for average residential levels relative to &lt;= 5 mg/L were 1.2 (0.7-2.0) for &gt; 5-10 mg/L and 1.1 (0.6-1.9) for &gt; 10 mg/L. The OR for subjects with longest exposure duration (&gt; 20 years) to highest levels (&gt; 9.5 mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for &gt; 8 vs. &lt;= 4 mg/day. Adjustment for several covariables showed similar results to crude analyses. Conclusion: Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed. (C) 2014 Elsevier Inc. All rights reserved

Nitrate and trace elements in municipal and bottled water in Spain Nitrato y elementos traza en agua embotellada y municipal en España

Objectives: To describe levels of nitrate and trace elements in drinking water from the study areas of a multicase-control study of cancer in Spain (MCC-Spain). Methods: A total of 227 tap water samples were randomly collected from 67 municipalities in 11 provinces and the nine most frequently consumed bottled water brands were sampled to measure levels of nitrate, arsenic, nickel, chromium, cadmium, lead, selenium and zinc. Results: The median nitrate level was 4.2mg/l (range<1-29.0), with similar levels in rural and urban municipalities (p=0.86). Trace elements were unquantifiable in 94% of tap water samples. Differences between areas were significant for nitrate (p<0.001) and arsenic (p=0.03). Only nitrate was quantifiable in bottled water (range 2.3-15.6mg/l). Conclusions: Nitrate levels in municipal water differed between regions and were below the regulatory limit in all samples, including bottled water. Trace element levels were low and mainly unquantifiable in tap and bottled water.<br>Objetivos: Determinar las concentraciones de nitrato y de elementos traza en el agua de consumo de las áreas del estudio Multicaso-Control de Cáncer en España (MCC-Spain). Métodos: Se tomaron al azar 227 muestras de agua municipal en 67 municipios de 11 provincias, y 9 muestras de las aguas embotelladas más consumidas, para cuantificar la cantidad presente de nitrato, arsénico, níquel, cromo, cadmio, plomo y zinc. Resultados: La mediana de las cifras de nitrato fue 4,2mg/l (rango<1-29,0), con similares resultados en municipios urbanos y rurales (p=0,86). Los elementos traza fueron incuantificables en el 94% de las muestras de agua municipal. Se observaron diferencias entre áreas para nitrato (p<0,001) y arsénico (p=0,03). Solo el nitrato fue cuantificable en el agua embotellada (rango 2,3-15,6mg/l). Conclusiones: La cantidad de nitrato en el agua municipal difiere entre regiones y es menor que el límite regulatorio en todas las muestras. Los elementos traza son mayormente incuantificables tanto en el agua municipal como en la embotellada

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case–Control Study in Spain and Italy

BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. METHODS: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). RESULTS: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65; http://dx.doi.org/10.1289/EHP155.We appreciate the contribution of the institutions and local governments that provided data on municipal water in Spain, particularly to J. Lázaro Arias Paredes (Mancomunidad de Canales del Taibilla, Murcia, Spain). We also thank F. Gallino (IRCCS, Istituto Nazionale dei Tumori, Milan, Italy), A. Tonini and C. Dellanoce (Ospedale Niguarda Cà Granda, Milan, Italy) for their collaboration in conducting the study. We appreciate the contribution of G. Sesana and D. Ravetta of the regional Environmental Health Agency “Arpa Lombardia” and the contribution of E. Zamparo and F. del Bianco of the Health Authority n.5 “Friuli Occidentale” for providing data on DBPs (disinfection by-products) in Italian drinking water. We thank L. Font-Ribera and L.A. Salas for comments on the draft manuscript and X. Basagaña for the contribution to the statistical approach.S

Calidad del agua: un enfoque multidisciplinario

El concepto integral de calidad del agua está aún muy poco desarrollado en México. Así, el objetivo de este libro es que especialistas en los diversos aspectos de la calidad del agua, compartan sus conocimientos y experiencias, con el fin de disponer de un enfoque multidisciplinario sobre las causas y consecuencias de la contaminación del agua, así como con soluciones para mejorar la calidad del agua en el país. Libro de texto de naturaleza multidisciplinaria para el nivel superior, con lenguaje técnico pero con explicaciones y definiciones que lo hacen comprensible sin pérdida del rigor académico.Índice: INTRODUCCIÓN Conceptos de calidad del agua: un enfoque multidisciplinario PROBLEMÁTICA 1. Calidad, una limitante más para la disponibilidad del agua 2. La contaminación del agua subterránea en México 3. La contaminación de las costas mexicanas 4. La contaminación difusa 5. Las especies exóticas como contaminación biológica del agua SOLUCIONES 6. Soluciones tecnológicas a la contaminación del agua 7. Soluciones ecológicas a la contaminación del agua 8. Soluciones de la teoría económica para la contaminación del agua GOBERNANZA Y CALIDAD DEL AGUA 9. Aspectos sociales sobre la calidad del agua y los ecosistemas acuáticos: un análisis de conflictos y controversias en torno al agua 10. El marco jurídico e institucional para la gestión de la calidad del agua en México CONCLUSIONES Calidad del agua: un enfoque multidisciplinari