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Influencia De La Ingesta De Polifenoles En El Desarrollo De Diferentes Tipos De Cáncer: Estudio Multicaso-Control MCC-Spain Facundo Ezequiel Vitelli Storelli

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Influencia De La Ingesta De Polifenoles En El Desarrollo De Diferentes Tipos De Cáncer: Estudio Multicaso-Control MCC-Spain Facundo Ezequiel Vitelli Storelli Influencia de la ingesta de polifenoles en el desarrollo de diferentes tipos de cáncer: estudio multicaso-control MCC-Spain Facundo Ezequiel Vitelli Storelli Programa de doctorado en Biomedicina y Ciencias de la Salud Departamento de Ciencias Biomédicas Directores de la tesis Juan Pablo Barrio Lera Tania Fernández Villa León, 2020 UNIVERSIDAD DE LEÓN Departamento de Ciencias Biomédicas Área de Medicina Preventiva y Salud Pública Tesis Doctoral Programa de doctorado en Biomedicina y Ciencias de la Salud INFLUENCIA DE LA INGESTA DE POLIFENOLES EN EL DESARROLLO DE DIFERENTES TIPOS DE CÁNCER: ESTUDIO MULTICASO-CONTROL MCC-SPAIN. “Influence of the intake of polyphenols in the development of different types of cancer: MCC-Spain multicase-control study.” DIRECTORES: Dr. Juan Pablo Barrio Lera Dra. Tania Fernández Villa Facundo Ezequiel Vitelli Storelli León, 2020 INFLUENCIA DE LA INGESTA DE POLIFENOLES EN EL DESARROLLO DE DIFERENTES TIPOS DE CÁNCER: ESTUDIO MULTICASO-CONTROL MCC-SPAIN. Tesis doctoral que presenta Facundo Ezequiel Vitelli Storelli inscrita en el Programa de Doctorado en Biomedicina y Ciencias de la Salud de la Universidad de León para aspirar al título de Doctor con Mención Internacional. León, Octubre de 2020 Directores de la Tesis Dr. Juan Pablo Barrio Lera Dra. Tania Fernández Villa vii viii El doctorando Facundo Ezequiel Vitelli Storelli y los directores de la tesis Juan Pablo Barrio Lera y Tania Fernández Villa garantizamos, al firmar esta tesis doctoral, que el trabajo ha sido realizado por el doctorando bajo la dirección de los directores de la tesis y hasta donde nuestro conocimiento alcanza, en la realización del trabajo, se han respetado los derechos de otros autores a ser citados, cuando se han utilizado sus resultados o publicaciones. En León, Octubre de 2020 Directores de la Tesis Doctorando Fdo.: Juan Pablo Barrio Lera Fdo.: Facundo Ezequiel Vitelli Storelli Fdo.: Tania Fernández Villa ix x INFORME DEL DIRECTOR DE LA TESIS El Dr. D. Juan Pablo Barrio Lera como Tutor y Director de la Tesis Doctoral titulada “Influencia de la ingesta de polifenoles en el desarrollo de diferentes tipos de cáncer: estudio multicaso-control MCC-Spain” realizado por Don Facundo Ezequiel Vitelli Storelli en el Programa de doctorado en Biomedicina y Ciencias de la Salud, informa favorablemente el depósito de la misma, dado que reúne las condiciones necesarias para su defensa. Lo que firmo en León, Octubre de 2020 Fdo.: Juan Pablo Barrio Lera xi xii INFORME DEL DIRECTOR DE LA TESIS La Dra. Dña. Tania Fernández Villa como Directora de la Tesis Doctoral titulada “Influencia de la ingesta de polifenoles en el desarrollo de diferentes tipos de cáncer: estudio multicaso-control MCC-Spain” realizado por Don Facundo Ezequiel Vitelli Storelli en el Programa de doctorado en Biomedicina y Ciencias de la Salud, informa favorablemente el depósito de la misma, dado que reúne las condiciones necesarias para su defensa. Lo que firmo, en León Octubre 2020 Fdo.: Tania Fernández Villa Escriba el texto aquí xiii xiv D. Facundo Ezequiel Vitelli Storelli declara que la memoria de la tesis presentada bajo el título “Influencia de la ingesta de polifenoles en el desarrollo de diferentes tipos de cáncer: estudio multicaso-control MCC-Spain” es, conforme al artículo 13.1 del R.D. 99/2011, de 28 de enero, un trabajo original de investigación, sin contribución significativa de otra persona que no aparezca reflejada en la misma, y citando adecuadamente la procedencia del contenido no original, conforme a la normativa vigente. Asimismo, declaro que este trabajo no ha sido presentado y no lo será en el futuro como tesis doctoral, en ninguna universidad o institución de investigación, en España o en el extranjero. Entiendo la política de tolerancia cero frente al plagio de la Universidad de León, la cual se reserva el derecho de retirar mi título de doctor y adoptar cuantas medidas procedan legalmente, en caso de incumplimiento de este compromiso. León, Octubre de 2020 Fdo.: Facundo Ezequiel Vitelli Storelli xv xvi El trabajo ha sido desarrollado en el Área de Medicina Preventiva y Salud Pública de la Universidad de León, habiéndose realizado una estancia internacional de cuatro meses de duración en el Departamento de “Clinical Sciences and Community Health” de la “Università degli studio di Milano” (Milán, Italia). Para la realización de la presente tesis doctoral se han tenido en cuenta los datos recogidos en el proyecto MCC-Spain financiado por “Acción transversal del Cáncer” aprobada por el Consejo de Ministros en 2007, por el Instituto de Salud Carlos III-FEDER, Gobierno de España (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034). xvii xviii “Siempre deberemos recordar que lo que tenemos, hemos logrado y somos, se debe en gran medida a lo que otros han sembrado en nosotros” Anónimo xix xx Agradecimientos xxi xxii Quiero agradecer, sin lugar a dudas, a mis padres Rodolfo y Lidia, por enseñarme todo aquello que no viene en los libros. A mi hermana Berni, a la que admiro y de quien aprendí a valorar la juventud y la amistad, de esas que bastan unos momentos para dibujarte una sonrisa. A mis directores, el Dr. Juan Pablo Barrio, por su confianza en mí e ilustrarme con su meticulosa metodología en la investigación, y a la Dra. Tania Fernández, por enseñarme a mejorar día a día, y por su enorme dedicación y paciencia. También, como no, al Dr. Antonio José Molina, quien desde el principio contribuyó a acrecentar mis conocimientos y me propuso nuevos retos. Desde luego, tampoco podría presentar esta tesis sin la ayuda del Dr. Vicente Martín, quien al igual que el Dr. Juan Pablo, depositó su confianza en mí, y que con muchísima paciencia me ayudó a escribir artículos y a crecer como científico. Tampoco sería posible sin los pilares del día a día, María, Alex, Laura, Rob, Ana e Isa, de quién me llevo muchísimos valores, conversaciones y momentos. A Muyas, Medina, Rafa y Monfi, cuatro enormes seres humanos, a los cuales tengo como hermanos. No puedo olvidar tampoco a los cientos y cientos de pacientes, sin cuya contribución nada de esto sería posible, sois nuestro pilar y motivación diaria. Gracias a todos y a los que he podido dejar en el tintero, por ser los cimientos para mi desarrollo personal y profesional. xxiv Índice xxv xxvi Introducción………………………………………………………………………………………………………………….………..…...10 1- Cáncer……………………………………………………………………………………………………………………………………12 1.1 -Concepto y etiopatogenia……………………………………………………………………………………………….12 1.2- Epidemiología…………………………………………………………………………………………………………………15 1.3- Cáncer de mama…………………………………………………………………………………………………………….17 1.4- Cáncer gástrico……………………………………………………………………………………………………………….23 2- Polifenoles………………………………………………………………………………………………………………………….…..27 - Flavonoides……………………………………………………………………………………………………………….………..29 - Lignanos……………………………………………………………………………………………………………………………..29 - Estilbenos .................................................................................................................................. 30 - Ácidos fenólicos ........................................................................................................................ 30 - Otros polifenoles ...................................................................................................................... 31 2.1- Absorción de polifenoles ..................................................................................................... 31 2.2- Polifenoles y dieta ............................................................................................................... 32 2.3- Papel de los polifenoles en CM y CG ................................................................................... 39 Objetivos……………………………………………………………………………………………………………………………………….40 Plan de trabajo……………………………………………………………………………………………………………………………….44 Metodología……..……………………………………………………………………………………………………………………………48 3- Metodología…………………………………………………………………………………………………………………………...50 3.1- Proyecto MCC-Spain ................................. ……………………………………………………………………….50 3.2 StoP-Project .......................................................................................................................... 54 Resultados……………………………………………………………………………………………………………………………………..56 4-Resultados………………………………………………………………………………………………………………………..………58 4.1 Desarrollo de algoritmos....................................................................................................... 58 4.2- Consumo de polifenoles y Cáncer de mama ....................................................................... 70 4.3- Consumo de polifenoles y Cáncer gástrico .......................................................................... 85 4.4- Metaanálisis sobre la ingesta de polifenoles y Cáncer gástrico: StoP-Project. ................... 94 Discusión……………………………………………………………………………………………………………………………………..98 5-Discusión………………………………………………………………………………………………………………………………..100 5.1-Polifenoles y cáncer de mama ............................................................................................ 100 5.2-Polifenoles y cáncer gástrico .............................................................................................. 104 5.3-Polifenoles y cáncer gástrico: StoP-project .......................................................................
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