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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">El c&#225;ncer colorrectal &#40;CCR&#41; es el tercer c&#225;ncer m&#225;s com&#250;n en todo el mundo&#44; con las tasas m&#225;s altas en las regiones desarrolladas&#44; y el segundo en cuanto a mortalidad<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a>&#46; En Espa&#241;a&#44; en 2018&#44; el CCR se mantuvo como el primer tipo de tumor diagnosticado&#44; con 37&#46;000 casos nuevos y 16&#46;600 muertes estimadas<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">2</span></a>&#44; y una tendencia ascendente<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">El desarrollo de CCR es un proceso multifactorial&#44; que incluye factores gen&#233;ticos y ambientales&#44; as&#237; como la interacci&#243;n de ambos<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">4</span></a>&#44; y multiet&#225;pico&#44; en el cual se van acumulando mutaciones que pueden dar lugar al tumor&#46; Los estilos de vida como el consumo de alcohol y de carnes procesadas o la inactividad f&#237;sica son algunos factores de riesgo para su desarrollo con fuerte evidencia&#44; as&#237; como la grasa corporal y una mayor altura alcanzada en la edad adulta<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Los antecedentes familiares &#40;AF&#41; de CCR son otro factor de riesgo conocido e incluyen tanto el riesgo gen&#233;tico como el riesgo ambiental compartido&#46; Una familia es semejante en cuanto a riesgo de enfermedad debido a factores biol&#243;gicos&#44; culturales y de comportamiento compartidos<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a>&#44; y se sabe que en torno a un 20&#37; de los casos de CCR se producen en personas con AF de CCR&#44; cuando se excluyen los s&#237;ndromes hereditarios<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">En la revisi&#243;n llevada a cabo se han encontrado diversos estudios epidemiol&#243;gicos y revisiones<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">7&#8211;9</span></a> en los que se ha analizado la historia familiar en relaci&#243;n con el riesgo de CCR&#46; Un metaan&#225;lisis<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> concluy&#243; que el riesgo de desarrollar CCR y s&#237;ndromes hereditarios era mayor en las personas con AF&#44; y que aumentaba con el n&#250;mero de AF y una edad temprana de diagn&#243;stico del familiar&#46; Tambi&#233;n se ha estudiado la asociaci&#243;n entre los estilos de vida y el CCR<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> y sus diferentes localizaciones<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">12&#44;13</span></a>&#46; Sin embargo&#44; pocos estudios relacionan los AF de CCR con los estilos de vida&#44; contribuyendo a trav&#233;s del ambiente compartido<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> o relacionando los AF con las diversas localizaciones del tumor<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">7&#44;15</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">El objetivo de este estudio es evaluar la asociaci&#243;n entre los AF de primer grado de CCR y el desarrollo de CCR&#44; seg&#250;n el n&#250;mero de familiares afectados&#44; la edad de diagn&#243;stico y la localizaci&#243;n del tumor&#44; as&#237; como relacionar los estilos de vida y la presencia o no de AF&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todo</span><p id="par0030" class="elsevierStylePara elsevierViewall">Las personas participantes forman parte del estudio MCC-Spain<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">16&#44;17</span></a>&#44; un estudio observacional&#44; multic&#233;ntrico&#44; multicaso-control&#44; realizado entre 2008 y 2013 en 23 hospitales de 12 provincias espa&#241;olas&#44; cuyo objetivo fue evaluar exposiciones ambientales y su interacci&#243;n con factores gen&#233;ticos para varios tumores&#44; entre ellos el CCR&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Poblaci&#243;n de estudio</span><p id="par0035" class="elsevierStylePara elsevierViewall">Todas las personas participantes ten&#237;an entre 20 y 85 a&#241;os&#44; resid&#237;an en el &#225;rea del hospital de reclutamiento de los casos como m&#237;nimo desde 6 meses antes de la entrevista y no ten&#237;an impedimentos f&#237;sicos ni de comunicaci&#243;n para responder a los cuestionarios&#46; Los casos de CCR fueron incidentes&#44; con diagn&#243;stico confirmado histol&#243;gicamente &#40;CIE-10&#58; C18&#44; C19&#44; C20&#44; D01&#46;0&#44; D01&#46;1&#44; D01&#46;2&#41;&#46; Para su captaci&#243;n&#44; el personal del estudio contact&#243; con ellos&#47;ellas en los hospitales seleccionados&#46; La tasa de participaci&#243;n de los casos fue del 68&#37;&#46; Para los controles&#44; la media fue del 53&#37; y vari&#243; seg&#250;n la regi&#243;n&#46; Los controles fueron seleccionados aleatoriamente de las listas poblacionales asignadas a m&#233;dicos de familia del &#225;rea de los hospitales donde se reclutaron los casos&#44; y con la misma distribuci&#243;n de sexo y edad &#40;&#177; 5 a&#241;os&#41;&#46; Para este an&#225;lisis&#44; tras eliminar aquellos&#47;as participantes de quienes no se ten&#237;an datos sobre las variables de inter&#233;s&#44; se incluyeron 1360 casos de CCR y 2857 controles &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Recogida de informaci&#243;n</span><p id="par0040" class="elsevierStylePara elsevierViewall">La informaci&#243;n epidemiol&#243;gica se obtuvo mediante entrevista personal y la informaci&#243;n sobre la dieta con un cuestionario de frecuencia de alimentos autocompletado&#59; ambas se almacenaron electr&#243;nicamente en un cuestionario informatizado&#46; De los datos disponibles se consideraron las siguientes variables&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Informaci&#243;n sobre la dieta&#58; consumo de alcohol&#44; de carnes rojas y procesadas&#44; vegetales y energ&#237;a total&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Datos sociodemogr&#225;ficos&#58; sexo&#44; edad&#44; nivel educativo &#40;estudios inferiores a primarios&#44; primarios&#44; secundarios y universitarios&#41; y &#225;rea de residencia &#40;Le&#243;n&#44; Barcelona&#44; Madrid&#44; zona norte que comprende Asturias&#44; Cantabria&#44; Guip&#250;zcoa y Navarra&#44; y zona sur que incluye Granada&#44; Huelva&#44; Murcia y Valencia&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Datos antropom&#233;tricos&#58; peso&#44; altura e &#237;ndice de masa corporal &#40;IMC&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Exposiciones medioambientales y estilos de vida&#58; consumo de alcohol &#40;basado en el consumo pasado entre los 30-40 a&#241;os y categorizado como &#171;no consumo&#47;consumo moderado&#187; menos de 12<span class="elsevierStyleHsp" style=""></span>g&#47;d&#237;a o &#171;abuso&#187;<span class="elsevierStyleHsp" style=""></span>&#62;12<span class="elsevierStyleHsp" style=""></span>g&#47;d&#237;a&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Actividad f&#237;sica&#44; teniendo en cuenta los &#250;ltimos 10 a&#241;os e incluyendo actividad f&#237;sica recreativa&#44; evaluada con MET&#44; unidad de medida del metabolismo&#44; categorizada como sedentarismo si &#8804;8 MET&#47;h a la semana o no sedentarismo si &#62;8 MET&#47;h a la semana&#46;</p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">La historia familiar de CCR incluy&#243; padre&#44; madre&#44; hermano&#47;a o hijo&#47;a afectado&#47;a&#46; Tambi&#233;n se dispon&#237;a de informaci&#243;n de la edad en el momento del diagn&#243;stico del familiar afectado&#46; La localizaci&#243;n del tumor se defini&#243; de acuerdo con su distribuci&#243;n anat&#243;mica&#58; colon proximal &#40;encima del nivel de la flexura espl&#233;nica o su inclusi&#243;n&#41;&#44; distal &#40;descendente y sigmoide&#41; y recto&#59; hab&#237;a casos sin localizaci&#243;n&#46; Con el cuestionario de frecuencia de alimentos se evalu&#243; la ingesta diet&#233;tica durante el a&#241;o anterior al reclutamiento&#44; recogiendo informaci&#243;n&#44; entre otra&#44; sobre consumo de vegetales &#40;g&#47;d&#237;a&#41;&#44; carnes rojas y procesadas &#40;g&#47;d&#237;a&#41;&#44; y energ&#237;a consumida &#40;kcal&#47;d&#237;a&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">An&#225;lisis estad&#237;stico</span><p id="par0075" class="elsevierStylePara elsevierViewall">Para caracterizar las variables cuantitativas se utilizaron medidas de centralizaci&#243;n &#40;media&#41; y dispersi&#243;n &#40;desviaci&#243;n est&#225;ndar&#41;&#44; y para las cualitativas&#44; frecuencias absolutas y relativas&#46; Para el an&#225;lisis univariante se utiliz&#243; la prueba de ji al cuadrado en el caso de las variables cualitativas&#44; y para las cuantitativas&#44; en funci&#243;n de la normalidad o no de su distribuci&#243;n&#44; se realizaron las pruebas de ANOVA y Kruskal-Wallis&#44; respectivamente&#46; Las <span class="elsevierStyleItalic">odds ratios</span> &#40;OR&#41; de la exposici&#243;n y sus intervalos de confianza del 95&#37; &#40;IC95&#37;&#41; se estimaron mediante modelos mixtos de regresi&#243;n log&#237;stica no condicional&#46; Se utilizaron dos modelos&#58; el b&#225;sico &#40;ORc&#41;&#44; que incluye el sexo&#44; la edad y el nivel educativo como variables de efectos fijos y el &#225;rea de residencia como variable de efecto aleatorio&#44; y el ajustado &#40;ORa&#41;&#44; que incluye&#44; adem&#225;s de las variables del modelo b&#225;sico&#44; el IMC &#40;&#60;25&#58; bajo peso o normopeso&#59; 25-29&#58; sobrepeso&#59; &#8805;30&#58; obesidad&#41;&#44; el sedentarismo &#40;s&#237;&#47;no&#41;&#44; el consumo de alcohol &#40;no o moderado&#47;abuso&#41;&#44; el consumo de carnes rojas y procesadas &#40;g&#47;d&#237;a&#41;&#44; el consumo de vegetales &#40;g&#47;d&#237;a&#41; y la energ&#237;a consumida &#40;kcal&#47;d&#237;a&#41;&#46; Todos los an&#225;lisis se realizaron con el <span class="elsevierStyleItalic">software</span> estad&#237;stico Stata v&#46;15&#46;1<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">18</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">&#201;tica</span><p id="par0080" class="elsevierStylePara elsevierViewall">El protocolo de MCC-Spain fue aprobado por los comit&#233;s de &#233;tica de las instituciones participantes&#44; y la participaci&#243;n fue voluntaria&#44; previa firma del consentimiento informado&#46; Se garantiz&#243; la confidencialidad cumpliendo la Ley Org&#225;nica 3&#47;2018&#44; de 5 de diciembre&#44; de Protecci&#243;n de datos personales y garant&#237;a de los derechos digitales&#44; y fueron dados de alta en la Agencia de Protecci&#243;n de Datos &#40;N&#250;mero 2102672171&#41;&#46; Se encuentran m&#225;s detalles sobre la organizaci&#243;n del proyecto en <a href="http://www.mccspain.org/">http&#58;&#47;&#47;www&#46;mccspain&#46;org</a>&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0085" class="elsevierStylePara elsevierViewall">Las caracter&#237;sticas de los casos y de los controles se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#46; En los casos&#44; la proporci&#243;n de hombres fue mayor&#44; presentaron una media de edad y un IMC m&#225;s altos&#44; eran m&#225;s sedentarios y consum&#237;an m&#225;s alcohol&#44; con un mayor porcentaje de AF de primer grado y un nivel de estudios m&#225;s bajo que los controles&#46; Adem&#225;s&#44; los casos presentaban un consumo medio menor de vegetales y mayor de carnes rojas y procesadas&#44; y de energ&#237;a&#46; Las diferencias entre ellos fueron significativas &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;000&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Se analizaron los factores de riesgo seg&#250;n la existencia o no de AF de primer grado para los controles &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; En el an&#225;lisis ajustado&#44; la edad y el consumo de carnes rojas y procesadas se asociaron con presentar AF&#44; de manera que&#44; a medida que aumentaba la edad&#44; se elevaba la probabilidad de presentar alg&#250;n AF de primer grado afectado&#44; un 1&#37; por a&#241;o cumplido &#40;ORa&#58; 1&#44;01&#59; IC95&#37;&#58;1&#44;00-1&#44;02&#41;&#46; Adem&#225;s&#44; aquellos con alg&#250;n AF de primer grado presentaron un menor consumo de vegetales &#40;ORa&#58; 0&#44;89&#59; IC95&#37;&#58; 0&#44;81-0&#44;89&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> se observa que la prevalencia de AF de primer grado entre los casos fue superior que entre los controles &#40;18&#44;53 vs&#46; 9&#44;63&#37;&#41;&#46; En comparaci&#243;n con las personas que no ten&#237;an AF&#44; presentarlos dobl&#243; la probabilidad de desarrollar CCR &#40;ORa&#58; 2&#44;19&#59; IC95&#37;&#58; 1&#44;80-2&#44;66&#41;&#44; con dos o m&#225;s AF de primer grado se increment&#243; hasta 4 veces &#40;ORa&#58; 4&#44;22&#59; IC95&#37;&#58; 2&#44;29-7&#44;78&#41; y con un familiar diagnosticado antes de los 50 a&#241;os hubo tres veces m&#225;s probabilidades &#40;ORa&#58; 3&#44;24&#59; IC95&#37;&#58; 1&#44;52-6&#44;91&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> se relacionan los AF con la localizaci&#243;n anat&#243;mica del tumor y con la edad en el momento del diagn&#243;stico de los casos&#46; La prevalencia de AF de primer grado en los diagnosticados de c&#225;ncer de colon y recto fue similar &#40;18&#44;24 vs&#46; 19&#44;13&#37;&#41;&#46; La influencia de los AF de primer grado en el tipo de CCR oscil&#243; entre una ORa de 1&#44;82 &#40;IC95&#37;&#58; 1&#44;33-2&#44;50&#41; para colon proximal y una ORa de 2&#44;42 &#40;IC95&#37;&#58; 1&#44;83-3&#44;20&#41; para colon distal &#40;diferencias no significativas&#41;&#46; En cuanto a la edad a la que se diagnostic&#243; el tumor&#44; los menores de 50 a&#241;os presentaron hasta cuatro veces m&#225;s probabilidades de tener AF que los controles &#40;ORa&#58; 4&#44;79&#59; IC95&#37;&#58; 2&#44;65-8&#44;65&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discusi&#243;n</span><p id="par0105" class="elsevierStylePara elsevierViewall">En este estudio&#44; basado en poblaci&#243;n espa&#241;ola&#44; se refuerza la hip&#243;tesis de que los AF de primer grado de CCR son un importante factor de riesgo para el desarrollo de este c&#225;ncer&#46; Los AF de CCR incrementaron hasta dos veces la probabilidad de presentarlo y hasta cuatro veces cuando se ten&#237;an dos o m&#225;s familiares afectados&#46; En cuanto a la edad del diagn&#243;stico&#44; la probabilidad de presentar CCR fue mayor cuando el AF fue diagnosticado antes de los 50 a&#241;os&#46; Adem&#225;s&#44; cuando exist&#237;an AF tambi&#233;n se hall&#243; una mayor probabilidad de desarrollar este tumor antes de los 50 a&#241;os&#46; Al relacionar los AF con la localizaci&#243;n del tumor no se encontraron diferencias significativas&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Los resultados obtenidos concuerdan con los informados en estudios previos&#44; en los cuales los AF de primer grado se asociaron con un incremento de la probabilidad de desarrollo de CCR entre 1&#44;41 y 2&#44;81<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">7&#44;8&#44;19&#8211;23</span></a>&#46; Del mismo modo&#44; el riesgo se increment&#243; con el aumento del n&#250;mero de familiares de primer grado afectados&#44; con riesgos similares a los encontrados en el presente estudio&#58; entre 1&#44;41 y 2&#44;25 en caso de un solo familiar<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">20&#8211;23</span></a> y entre 3&#44;95 y 4&#44;25 en caso de dos o m&#225;s familiares afectados<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">20&#8211;23</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">La raz&#243;n de que los AF influyan en el desarrollo de CCR y de que el riesgo se incremente al aumentar el n&#250;mero de familiares afectados es&#44; por un lado&#44; la herencia debida a mutaciones en l&#237;neas germinales&#44; que van a dar lugar a los diversos s&#237;ndromes&#44; pero estos solo representan una peque&#241;a proporci&#243;n del total &#40;5-13&#37;&#41;&#46; Por otro lado&#44; la agrupaci&#243;n familiar representa un 25-30&#37; de los casos cuando se omiten los s&#237;ndromes gen&#233;ticos<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a>&#44; por lo que otros genes de baja penetrancia junto con el ambiente compartido en familia van a influir de manera importante&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">El presente estudio hall&#243; una mayor probabilidad de desarrollar CCR cuando hab&#237;a un AF diagnosticado antes de los 50 a&#241;os&#46; Otros estudios indican riesgos muy similares en las personas con AF diagnosticadas antes de los 50 a&#241;os &#40;3&#44;32-3&#44;55&#41;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a>&#44; y de 2&#44;18 si el AF fue diagnosticado con 50 o m&#225;s a&#241;os<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a>&#46; La explicaci&#243;n a este hallazgo ser&#237;a que cabe esperar una mayor carga gen&#233;tica en aquellas personas diagnosticadas antes de los 50 a&#241;os&#44; mientras que en edades m&#225;s avanzadas&#44; al estar expuestos durante m&#225;s tiempo a factores de riesgo&#44; influir&#225;n m&#225;s las mutaciones adquiridas&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Las causas de desarrollo de CCR se pueden desdoblar en la herencia gen&#233;tica&#44; el ambiente &#250;nico de cada individuo y el mencionado ambiente compartido en familia&#46; En el presente estudio se encontraron diferencias entre los factores de riesgo de los controles que ten&#237;an o no AF de primer grado&#46; En ciertos aspectos&#44; como el consumo de vegetales&#44; exist&#237;a una influencia de este ambiente compartido&#46; En un estudio realizado en gemelos<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> se atribuy&#243; al ambiente compartido un 16&#37; para el c&#225;ncer de colon y un 10&#37; para el de recto&#46; En otro estudio realizado con familias adoptivas<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a>&#44; en las que la persona adoptada procedente de una familia biol&#243;gica afectada se ver&#237;a influida por la herencia biol&#243;gica o gen&#233;tica&#44; y la persona adoptada con familia adoptiva afectada se ver&#237;a influida por la herencia ambiental&#44; se encontr&#243; que en el primer supuesto exist&#237;a mayor probabilidad de desarrollo de la enfermedad&#44; mientras que en el segundo aumentaba el riesgo&#44; pero no de manera significativa&#46; Iba&#241;ez-Sanz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> afirman que los AF son el factor de riesgo m&#225;s fuerte para el desarrollo de CCR y que se asocia sobre todo a la gen&#233;tica&#44; pero tambi&#233;n la historia familiar podr&#237;a contribuir debido al ambiente familiar compartido&#46; No obstante&#44; que el CCR sea un proceso multifactorial hace que estos tres aspectos no puedan considerase por separado&#44; ya que es bien conocido que existen interacciones del ambiente y la gen&#233;tica<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">27&#44;28</span></a>&#44; de manera que&#44; hipot&#233;ticamente&#44; si intervenimos en uno de ellos conseguiremos modificaciones en el otro&#46; Cho et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> sugieren que el riesgo gen&#233;tico puede ser atenuado por unos estilos de vida saludables&#46; Adem&#225;s&#44; en un gran estudio de casos y controles<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> se identific&#243; que una combinaci&#243;n de estilos de vida saludables &#40;no fumar&#44; consumo de alcohol recomendado&#44; dieta saludable&#44; pr&#225;ctica de actividad f&#237;sica recomendada y peso saludable o normopeso&#41; parece reducir el riesgo de CCR independientemente del perfil gen&#233;tico del paciente&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Si bien en el presente trabajo no se hallaron diferencias significativas en cuanto a la localizaci&#243;n del CCR&#44; algunos autores indican que los AF tienen un mayor impacto en los tumores proximales<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> y otros afirman que son m&#225;s probables en el colon que en el recto<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a>&#44; en concreto en el colon distal<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a>&#46; Se cree que estos &#250;ltimos son m&#225;s inestables y pueden surgir por los mismos mecanismos que el CCR asociado a poliposis&#44; mientras que los proximales representan una forma gen&#233;ticamente m&#225;s estable y pueden desarrollarse por los mismos mecanismos que el CCR hereditario no asociado a poliposis<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">30&#44;31</span></a>&#46; Un estudio<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> relacion&#243; la localizaci&#243;n del tumor con diversas exposiciones ambientales&#44; y encontr&#243; que las relaciones del CCR con la actividad f&#237;sica&#44; las medidas antropom&#233;tricas y el consumo de tabaco difer&#237;an seg&#250;n la regi&#243;n anat&#243;mica donde se desarrollaba el tumor&#46; A pesar de que no analiza la historia familiar de CCR&#44; apoya la hip&#243;tesis de que los tumores en diferentes regiones anat&#243;micas pueden tener etiolog&#237;as distintas&#44; adem&#225;s de evidenciar una vez m&#225;s la importancia de los factores ambientales en el desarrollo de CCR&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Por lo tanto&#44; los factores ambientales en interacci&#243;n con la gen&#233;tica tienen un papel relevante en el desarrollo de CCR&#46; Dichos factores son potencialmente modificables y&#44; por lo tanto&#44; en aquellas personas con AF es posible llevar a cabo acciones encaminadas a disminuir el riesgo de desarrollo de este tumor&#46; Las creencias y los comportamientos personales son un aspecto dif&#237;cil de modificar&#59; sin embargo&#44; en diversas patolog&#237;as se ha encontrado como factor motivacional para el cambio la percepci&#243;n del riesgo de enfermedad&#46; Esta percepci&#243;n del riesgo es mayor en las personas que presentan AF&#44; y a medida que se incrementa la percepci&#243;n del riesgo aumenta la motivaci&#243;n para modificar los estilos de vida<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">32&#44;33</span></a>&#46; Por tanto&#44; esto puede usarse como una herramienta de prevenci&#243;n personalizada &#40;tanto para la modificaci&#243;n de h&#225;bitos como para la participaci&#243;n en cribados&#41;&#44; lo cual est&#225; demostrado que tiene m&#225;s efectividad que los mensajes generalizados<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">En el presente estudio solo se han analizado los AF de primer grado&#44; pero estudios previos analizaron los AF de segundo y hasta tercer grado&#46; Presentar AF de primer grado influye mucho m&#225;s en el riesgo de CCR&#44; e incluso&#44; cuando se combinan&#44; puede aumentar significativamente el riesgo<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a>&#46; Debido a que los AF de segundo o tercer grado se recuerdan peor que los de primer grado&#44; solo se han analizado estos &#250;ltimos&#44; ya que podr&#237;a suponer una limitaci&#243;n&#44; pues se trata de un dato autorreportado&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Aparte de las limitaciones propias de los estudios de casos y controles<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a>&#44; deben considerarse otras limitaciones&#46; Por un lado&#44; los datos sobre alimentaci&#243;n se recogieron con un cuestionario y podr&#237;an estar sujetos a errores de medici&#243;n&#44; pero se utiliz&#243; el cuestionario de frecuencia de alimentos previamente validado para poblaci&#243;n espa&#241;ola y los datos agregados de grupos de alimentos se corrigieron mediante preguntas cruzadas&#46; El uso de datos autorreportados para variables como el IMC y la actividad f&#237;sica &#40;1 o 2 a&#241;os antes de la entrevista&#41; tambi&#233;n podr&#237;a llevar a un sesgo de recuerdo&#44; pero si existiera probablemente ser&#237;a no diferencial&#44; lo que implicar&#237;a una subestimaci&#243;n de los efectos estudiados&#46; Para evitar el posible sesgo de selecci&#243;n de casos&#44; se pretendi&#243; reclutar todos los casos con un primer diagn&#243;stico de c&#225;ncer&#44; asegurando pocos casos perdidos&#46; Existe un sesgo de participaci&#243;n en los controles con mayor nivel educativo y tambi&#233;n es posible que los controles con m&#225;s AF de c&#225;ncer &#40;no espec&#237;ficamente CCR&#41; aceptaran participar en mayor medida&#44; pero si as&#237; fuera solo infraestimar&#237;a las asociaciones&#46; Finalmente&#44; en los an&#225;lisis se realizaron ajustes para las variables mencionadas con el fin de conseguir reducir ese factor de confusi&#243;n&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">En cuanto a los puntos fuertes del estudio&#44; cabe mencionar el tama&#241;o muestral&#44; que los casos de CCR analizados son incidentes y que su diagn&#243;stico fue confirmado histol&#243;gicamente&#44; proporcionando informaci&#243;n espec&#237;fica sobre el subtipo de tumor&#46; Esto permiti&#243; detectar asociaciones entre el subtipo de tumor y los AF&#46; En cuanto a la selecci&#243;n de los controles&#44; hacerlo a partir de las listas de m&#233;dicos generales proporcion&#243; una muestra de base poblacional&#44; dada la cobertura p&#250;blica universal del Sistema Nacional de Salud en Espa&#241;a&#44; lo cual es otra de las fortalezas del estudio&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Tambi&#233;n es una fortaleza que se trata de un estudio multic&#233;ntrico&#44; realizado en numerosas regiones de Espa&#241;a&#44; incluyendo zonas urbanas y rurales&#44; con una amplia variabilidad geogr&#225;fica de los datos&#44; especialmente de aquellos relativos a ingestas diet&#233;ticas&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusiones</span><p id="par0160" class="elsevierStylePara elsevierViewall">Las personas con AF de primer grado presentan mayor riesgo de desarrollar CCR que aquellas sin AF&#44; y este riesgo se incrementa a medida que aumenta el n&#250;mero de familiares de primer grado afectados y cuando estos fueron diagnosticados antes de los 50 a&#241;os&#46;<elsevierMultimedia ident="tb0005"></elsevierMultimedia></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Editora responsable del art&#237;culo</span><p id="par0195" class="elsevierStylePara elsevierViewall">Clara Berm&#250;dez-Tamayo&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Declaraci&#243;n de transparencia</span><p id="par0200" class="elsevierStylePara elsevierViewall">La autora principal &#40;garante responsable del manuscrito&#41; afirma que este manuscrito es un reporte honesto&#44; preciso y transparente del estudio que se remite a <span class="elsevierStyleSmallCaps">Gaceta Sanitaria&#44;</span> que no se han omitido aspectos importantes del estudio&#44; y que las discrepancias del estudio seg&#250;n lo previsto &#40;y&#44; si son relevantes&#44; registradas&#41; se han explicado&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Contribuciones de autor&#237;a</span><p id="par0205" class="elsevierStylePara elsevierViewall">Conceptualizaci&#243;n&#58; M&#46; Rub&#237;n-Garc&#237;a&#44; V&#46; Mart&#237;n y T&#46; Fern&#225;ndez-Villa&#46; Metodolog&#237;a&#58; M&#46; Rub&#237;n-Garc&#237;a&#44; V&#46; Mart&#237;n y Y&#46; Benavente&#46; An&#225;lisis formal&#58; M&#46; Rub&#237;n-Garc&#237;a y V&#46; Mart&#237;n&#46; Redacci&#243;n y preparaci&#243;n del borrador&#58; M&#46; Rub&#237;n-Garc&#237;a&#44; V&#46; Mart&#237;n&#44; F&#46; Vitelli-Storelli&#44; L&#46; &#193;lvarez-&#193;lvarez&#44; T&#46; Fern&#225;ndez-Villa y Y&#46; Benavente&#46; Revisi&#243;n y edici&#243;n&#58; M&#46; Rub&#237;n-Garc&#237;a&#44; V&#46; Mart&#237;n&#44; F&#46; Vitelli-Storelli&#44; V&#46; Moreno&#44; N&#46; Aragon&#233;s&#44; E&#46; Adarnaz&#44; J&#46; Alonso-Molero&#44; J&#46;J&#46; Jim&#233;nez-Mole&#243;n&#44; P&#46; Amiano&#44; G&#46; Fern&#225;ndez-Tard&#243;n&#44; A&#46; Molina-Barcel&#243;&#44; J&#46; Alguacil&#44; M&#46; Dolores-Chirlaque&#44; L&#46; &#193;lvarez-&#193;lvarez&#44; B&#46; P&#233;rez-G&#243;mez&#44; T&#46; Dierssen-Sotos&#44; R&#46; Olmedo-Requena&#44; M&#46; Guevara&#44; T&#46; Fern&#225;ndez-Villa&#44; M&#46; Poll&#225;n y Y&#46; Benavente&#46; Supervisi&#243;n&#58; V&#46; Mart&#237;n y T&#46; Fern&#225;ndez-Villa&#46; Administraci&#243;n del proyecto&#58; N&#46; Aragon&#233;s y M&#46; Poll&#225;n&#46; Adquisici&#243;n de financiaci&#243;n&#58; V&#46; Mart&#237;n&#44; V&#46; Moreno&#44; N&#46; Aragon&#233;s&#44; E&#46; Adarnaz&#44; J&#46;J&#46; Jim&#233;nez-Mole&#243;n&#44; P&#46; Amiano&#44; G&#46; Fern&#225;ndez-Tard&#243;n&#44; J&#46; Alguacil&#44; B&#46; P&#233;rez-G&#243;mez&#44; T&#46; Dierssen-Sotos&#44; M&#46; Poll&#225;n y Y&#46; Benavente&#46; Todas las personas firmantes han le&#237;do y aceptado la versi&#243;n final del manuscrito&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Agradecimientos</span><p id="par0210" class="elsevierStylePara elsevierViewall">A la Dra&#46; Gemma Casta&#241;o Vinyals y al Dr&#46; Manolis Kogevinas por su colaboraci&#243;n en el proyecto&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Financiaci&#243;n</span><p id="par0215" class="elsevierStylePara elsevierViewall">El estudio fue parcialmente financiado por la &#171;Acci&#243;n Transversal del C&#225;ncer&#187;&#44; aprobada por el Consejo del Ministerio de Espa&#241;a el 11 de octubre de 2007&#44; por el Instituto de Salud Carlos III-FEDER &#40;PI08 &#47; 1770&#44; PI08 &#47; 0533&#44; PI08 &#47; 1359&#44; PS09 &#47; 00773-Cantabria&#44; PS09 &#47; 01286-Le&#243;n&#44; PS09 &#47; 01903-Valencia&#44; PS09 &#47; 02078-Huelva&#44; PS09 &#47; 01662-Granada&#44; PI11 &#47; 01403&#44; PI11 &#47; 01889-FEDER&#44; PI11 &#47; 00226&#44; PI11 &#47; 01810&#44; PI11 &#47; 02213&#44; PI12 &#47; 00488&#44; PI12 &#47; 00265&#44; PI12 &#47; 01270&#44; PI12 &#47; 00715&#44; PI12 &#47; 00150&#44; PI14 &#47; 01219&#44; PI14 &#47; 0613&#44; PI15 &#47; 00069&#44; PI15 &#47; 00914&#44; PI15 &#47; 01032&#44; PI17CIII &#47; 00034&#41;&#44; as&#237; como a trav&#233;s de CIBERESP CB06&#47;02&#47;0073&#44; cofinanciado por el Fondo Europeo de Desarrollo Regional &#40;FEDER&#41;&#46; Tambi&#233;n cuenta con el apoyo de la Fundaci&#243;n Marqu&#233;s de Valdecilla &#40;API 10&#47;09&#41;&#44; el ICGC International Cancer Genome Consortium CLL &#40;el proyecto ICGC CLL-Genome Project est&#225; financiado por el Ministerio de Econom&#237;a y Competitividad espa&#241;ol a trav&#233;s del Instituto de Salud Carlos III y la Red Tem&#225;tica de Investigaci&#243;n del C&#225;ncer del Instituto de Salud Carlos III &#91;RD12 &#47; 0036&#47;0036&#93;&#41;&#44; la Junta de Castilla y Le&#243;n &#40;LE22A10-2&#41;&#44; la Consejer&#237;a de Salud de la Junta de Andaluc&#237;a &#40;PI-0571-2009&#44; PI-0306-2011&#44; salud201200057018tra&#41;&#44; la Conselleria de Sanitat de la Generalitat Valenciana &#40;AP&#95;061&#47;10&#41;&#44; RecerCaixa &#40;2010ACUP 00310&#41;&#44; el Gobierno Regional del Pa&#237;s Vasco&#44; la Consejer&#237;a de Sanidad de la Regi&#243;n de Murcia&#44; la Comisi&#243;n Europea de subvenciones FOOD-CT-2006-036224-HIWATE&#44; la Fundaci&#243;n Cient&#237;fica de la Asociaci&#243;n Espa&#241;ola Contra el C&#225;ncer &#40;AECC&#41;&#44; la Generalitat de Catalunya - Agencia de Gesti&#243;n Universitaria e Investigaci&#243;n Becas &#40;AGAUR&#41; y 2017SGR01085&#46; Becas 2017SGR723 y 2014SGR850 de la Fundaci&#243;n Caja de Ahorros de Asturias y de la Universidad de Oviedo&#46; ISGlobal agradece el apoyo del Ministerio de Ciencia e Innovaci&#243;n de Espa&#241;a a trav&#233;s del Programa Centro de Excelencia Severo Ochoa 2019-2023 &#40;CEX2018-000806-S&#41;&#44; y el apoyo de la Generalitat de Catalunya a trav&#233;s del Programa CERCA&#46; M&#46; Rub&#237;n-Garc&#237;a cuenta con el apoyo del Ministerio de Educaci&#243;n de Espa&#241;a &#40;FPU17&#47;06488&#41;&#46; Fundaci&#243;n Cient&#237;fica de la Asociaci&#243;n Espa&#241;ola Contra el C&#225;ncer &#40;AECC&#41;&#44; ayuda GCTRA18022MORE&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicto de intereses</span><p id="par0220" class="elsevierStylePara elsevierViewall">Ninguno&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio es evaluar la asociaci&#243;n entre antecedentes familiares &#40;AF&#41; de primer grado y c&#225;ncer colorrectal &#40;CCR&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 2857 controles y 1360 casos de CCR&#44; del estudio MCC-Spain&#46; La <span class="elsevierStyleItalic">odds ratio</span> &#40;OR&#41; y el intervalo de confianza del 95&#37; &#40;IC95&#37;&#41; de los AF de primer grado y el CCR se estimaron mediante regresi&#243;n log&#237;stica no condicional seg&#250;n la localizaci&#243;n tumoral en los casos&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Los AF de primer grado duplicaron el riesgo de CCR &#40;OR&#58; 2&#44;19&#59; IC95&#37;&#58; 1&#44;80-2&#44;66&#41;&#44; increment&#225;ndose en aquellos que presentaban dos o m&#225;s &#40;OR&#58; 4&#44;22&#59; IC95&#37;&#58; 2&#44;29-7&#44;78&#41; y en aquellos cuyos familiares fueron diagnosticados antes de los 50 a&#241;os &#40;OR&#58; 3&#44;24&#59; IC95&#37;&#58; 1&#44;52-6&#44;91&#41;&#46; Presentar AF se relacion&#243; con estilos de vida como un menor consumo de vegetales&#46; En cuanto a la asociaci&#243;n de los AF con la localizaci&#243;n no se observaron diferencias significativas entre colon y recto&#44; pero s&#237; en la relaci&#243;n de estas con la edad de diagn&#243;stico&#44; presentando m&#225;s AF los diagnosticados antes de los 50 a&#241;os &#40;OR&#58; 4&#44;79&#59; IC95&#37;&#58; 2&#44;65-8&#44;65&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Presentar AF de primer grado de CCR aumenta las probabilidades de desarrollar este c&#225;ncer&#44; y tambi&#233;n se elevan cuando el familiar es diagnosticado a edad temprana&#46; Por ello&#44; debe ser una poblaci&#243;n diana sobre la que incrementar las medidas de prevenci&#243;n&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
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            "titulo" => "M&#233;todo"
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          2 => array:2 [
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            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusiones"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To evaluate the association between first-degree family history and colorectal cancer &#40;CRC&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Method</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We analyzed data from 2857 controls and 1360 CRC cases&#44; collected in the MCC-Spain project&#46; The adjusted odds ratio &#40;OR&#41; and 95&#37; confidence interval &#40;95&#37; <span class="elsevierStyleSmallCaps">C</span>I&#41; of association with the family history of CRC was estimated by non-conditional logistic regression&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">First-degree relatives doubled the risk of CRC &#40;OR&#58; 2&#46;19&#59; 95&#37; CI&#58; 1&#46;80&#8211;2&#46;66&#41;&#44; increasing in those with two or more &#40;OR&#58; 4&#46;22&#59; 95&#37; CI&#58; 2&#46;29&#8211;7&#46;78&#41; and in those whose relatives were diagnosed before 50 years &#40;OR&#58; 3&#46;24&#59; 95&#37; CI&#58; 1&#46;52&#8211;6&#46;91&#41;&#46; Regarding the association of the family history with the location&#44; no significant differences were observed between colon and rectum&#44; but there were in the relation of these with the age of diagnosis&#44; having more relatives those diagnosed before 50 years &#40;OR&#58; 4&#46;79&#59; 95&#37; CI&#58; 2&#46;65&#8211;8&#46;65&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">First-degree relatives of CRC increase the chances of developing this tumor&#44; they also increase when the relative is diagnosed at an early age&#46; Therefore&#44; it must be a target population on which to carry out prevention measures&#46;</p></span>"
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            "titulo" => "Results"
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            "titulo" => "Conclusions"
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        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "etiqueta" => "Tabla 1"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">AF&#58; antecedentes familiares&#59; DE&#58; desviaci&#243;n est&#225;ndar&#59; IMC&#58; &#237;ndice de masa corporal&#46;</p>"
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                  \t\t\t\t">894&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">392&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28&#44;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;000</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primarios&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">927&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">32&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">523&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#44;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Secundarios&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">851&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;79&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">292&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">21&#44;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;687</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1642&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">63&#44;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">188&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;86-1&#44;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Consumo de alcohol</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&#47;moderado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1567&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">172&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;992</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abuso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#44;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;80-1&#44;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Edad &#40;media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;00-1&#44;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;090&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Vegetales &#40;100 g&#47;d&#237;a&#41; &#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;81-0&#44;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Carnes rojas y procesadas &#40;100 g&#47;d&#237;a&#41; &#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;86-1&#44;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;437&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Energ&#237;a &#40;1000 kcal&#47;d&#237;a&#41; &#40;media</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;94-1&#44;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;220&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IC95&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IC95&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">No AF primer grado&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Ref&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">S&#237; AF primer grado&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 familiar afectado&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Datos faltantes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2950166.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Ajustada por sexo&#44; edad&#44; nivel educativo y &#225;rea de residencia&#46;</p>"
            ]
            1 => array:3 [
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