An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population.

PURPOSE: Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. METHODS: This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. RESULTS: The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52 years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. CONCLUSIONS: This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

[Response to hypoxia. A systemic mechanism based on the control of gene expression]. / Respuesta a la hipoxia. Un mecanismo sistemico basado en el control de la expresion genica.

New, critically important data have been recently generated about the response to hypoxia. This response can be schematized in three main systems or functions, ie, detectional or oxygen sensing, regulatory, which controls gene expression and effector. The principal organizer of the regulatory branch is a specific transcription factor, the hypoxia-inducible factor 1 (HIF-1). In the presence of oxygen, the alpha subunit of HIF-1 (HIF-1alpha) is modified by hydroxylases, that represent the central point of the oxygen sensing mechanism. This type of hydroxylation induces HIF-1alpha catabolism by the proteosome. On the contrary, in hypoxia, or in the presence of certain growth factors that increase HIF-1alpha synthesis, HIF-1alpha translocates to the nucleus, where it binds HIF-1beta, and thence acts on transcription of genes carrying hypoxia responsive elements (HRE) on their promoters. These genes regulate the synthesis of an ample series of proteins, which span from respiratory enzymes and transporters to hormones regulating circulation and erythropoiesis. The role of HIF-1alpha is not restricted to the mere induction of adaptation to decreased oxygen: instead, it significantly participates in cell repairing mechanisms. A simple list of some of the stimulatory or inhibitory alterations of pathophysiological importance involving the HIF-1 system, would include: chronic lung disease, smoking adaptation, anemia/hemorrhage, ischemia/reperfusion, growth, vascularization and cell resistance of tumors, preeclampsia and intrauterine growth retardation, retinal hyper o hypovascularization, drug intoxications, bowel inflammatory disease and wound repair. This list illustrates by itself the importance of the mechanism herein reviewed.

Respuesta a la hipoxia: un mecanismo sistemico basado en el control de la expresion genica / Response to hypoxia: a systemic mechanism based on the control of gene expression

La respuesta hipóxica, sobre la que se dispone de nuevos datos críticamente importantes, puede esquematizarse en tres sistemas, vg. de detección o sensor de oxígeno, de regulación, que controla la expresión génica y efector. El elemento principal de organización del sistema regulador es un factor de transcripción específico, el factor inducible por hipoxia 1 (HIF-1). En presencia de oxígeno, la subunidad α del HIF-1 (HIF-1α) se modifica por las hidroxilasas, que constituyen el punto central del mecanismo sensor, induciendo su catabolismo por el proteosoma. Por el contrario, en hipoxia, o en presencia de algunos factores de crecimiento que incrementan su síntesis, el HIF-1α se transloca al núcleo, donde, unido al HIF-1β, actúa como factor transcripcional de genes con elementos de respuesta hipóxica (HRE) en su promotor. Estos regulan lasíntesis de una amplia serie de proteínas, que abarcan desde enzimas respiratorias y transportadores hasta hormonas involucradas en la regulación a escala del organismo de la circulación y la eritropoyesis. El papel del HIF-1 no se restringe a la mera inducción de una respuesta adaptativa a la falta de oxígeno, sino que participa significativamente en los mecanismos de reparación celular. Una simple lista de algunas alteraciones de importÔncia fisiopatológica, tanto estimulatorias como inhibitorias, que involucran al sistema de HIF-1, incluiría: enfermedad pulmonar crónica, adaptación al tabaco/humo, anemia/hemorragia, isquemia/reperfusión, crecimiento, vascularización y resistencia celular de los tumores, preeclampsia y crecimiento intrauterino retardado, hiper o hipovascularización retiniana, sobredosis de fármacos, enfermedad inflamatoria intestinal y curación de heridas. Esta sola enumeración ilustra la importancia de este mecanismo. (AU).

New, critically important data have been recently generated about the response to hypoxia. This response can be schematized in three main systems or functions, ie, detectional or oxygen sensing, regulatory, which controls gene expression and effector. The principal organizer of the regulatory branch is a specific transcription factor, the hypoxia-inducible factor 1 (HIF-1). In the presence of oxygen, the α subunit of HIF-1 (HIF-1α) is modified by hydroxylases, that represent the central point of the oxygen sensing mechanism. This type of hydroxylation induces HIF-1α catabolism by the proteosome. On the contrary, in hypoxia, or in the presence of certain growth factors that increase HIF-1α synthesis, HIF-1α translocates to the nucleus, where it binds HIF-1β, and thence acts on transcription of genes carrying hypoxia responsive elements (HRE) on their promoters. These genes regulate the synthesis of an ample series of proteins, which span from respiratory enzymes and transporters to hormones regulating circulation and erythropoiesis. The role of HIF-1α is not restricted to the mere induction of adaptation to decreased oxygen: instead, it significantly participates in cell repairing mechanisms. A simple list of some of the stimulatory or inhibitory alterations of pathophysiological importance involving the HIF-1 system, would include: chronic lung disease, smoking adaptation, anemia/hemorrhage, ischemia/reperfusion, growth, vascularization and cell resistance of tumors, preeclampsia and intrauterine growth retardation, retinal hyper ohypovascularization, drug intoxications, bowel inflammatory disease and wound repair. This list illustrates by itself the importance of the mechanism herein reviewed. (AU)

Respuesta a la hipoxia: un mecanismo sistemico basado en el control de la expresion genica / Response to hypoxia: a systemic mechanism based on the control of gene expression

La respuesta hipóxica, sobre la que se dispone de nuevos datos críticamente importantes, puede esquematizarse en tres sistemas, vg. de detección o sensor de oxígeno, de regulación, que controla la expresión génica y efector. El elemento principal de organización del sistema regulador es un factor de transcripción específico, el factor inducible por hipoxia 1 (HIF-1). En presencia de oxígeno, la subunidad α del HIF-1 (HIF-1α) se modifica por las hidroxilasas, que constituyen el punto central del mecanismo sensor, induciendo su catabolismo por el proteosoma. Por el contrario, en hipoxia, o en presencia de algunos factores de crecimiento que incrementan su síntesis, el HIF-1α se transloca al núcleo, donde, unido al HIF-1β, actúa como factor transcripcional de genes con elementos de respuesta hipóxica (HRE) en su promotor. Estos regulan lasíntesis de una amplia serie de proteínas, que abarcan desde enzimas respiratorias y transportadores hasta hormonas involucradas en la regulación a escala del organismo de la circulación y la eritropoyesis. El papel del HIF-1 no se restringe a la mera inducción de una respuesta adaptativa a la falta de oxígeno, sino que participa significativamente en los mecanismos de reparación celular. Una simple lista de algunas alteraciones de importÔncia fisiopatológica, tanto estimulatorias como inhibitorias, que involucran al sistema de HIF-1, incluiría: enfermedad pulmonar crónica, adaptación al tabaco/humo, anemia/hemorragia, isquemia/reperfusión, crecimiento, vascularización y resistencia celular de los tumores, preeclampsia y crecimiento intrauterino retardado, hiper o hipovascularización retiniana, sobredosis de fármacos, enfermedad inflamatoria intestinal y curación de heridas. Esta sola enumeración ilustra la importancia de este mecanismo. (AU).

New, critically important data have been recently generated about the response to hypoxia. This response can be schematized in three main systems or functions, ie, detectional or oxygen sensing, regulatory, which controls gene expression and effector. The principal organizer of the regulatory branch is a specific transcription factor, the hypoxia-inducible factor 1 (HIF-1). In the presence of oxygen, the α subunit of HIF-1 (HIF-1α) is modified by hydroxylases, that represent the central point of the oxygen sensing mechanism. This type of hydroxylation induces HIF-1α catabolism by the proteosome. On the contrary, in hypoxia, or in the presence of certain growth factors that increase HIF-1α synthesis, HIF-1α translocates to the nucleus, where it binds HIF-1β, and thence acts on transcription of genes carrying hypoxia responsive elements (HRE) on their promoters. These genes regulate the synthesis of an ample series of proteins, which span from respiratory enzymes and transporters to hormones regulating circulation and erythropoiesis. The role of HIF-1α is not restricted to the mere induction of adaptation to decreased oxygen: instead, it significantly participates in cell repairing mechanisms. A simple list of some of the stimulatory or inhibitory alterations of pathophysiological importance involving the HIF-1 system, would include: chronic lung disease, smoking adaptation, anemia/hemorrhage, ischemia/reperfusion, growth, vascularization and cell resistance of tumors, preeclampsia and intrauterine growth retardation, retinal hyper ohypovascularization, drug intoxications, bowel inflammatory disease and wound repair. This list illustrates by itself the importance of the mechanism herein reviewed. (AU)

Respuesta a la hipoxia: un mecanismo sistemico basado en el control de la expresion genica / Response to hypoxia: a systemic mechanism based on the control of gene expression

La respuesta hipóxica, sobre la que se dispone de nuevos datos críticamente importantes, puede esquematizarse en tres sistemas, vg. de detección o sensor de oxígeno, de regulación, que controla la expresión génica y efector. El elemento principal de organización del sistema regulador es un factor de transcripción específico, el factor inducible por hipoxia 1 (HIF-1). En presencia de oxígeno, la subunidad α del HIF-1 (HIF-1α) se modifica por las hidroxilasas, que constituyen el punto central del mecanismo sensor, induciendo su catabolismo por el proteosoma. Por el contrario, en hipoxia, o en presencia de algunos factores de crecimiento que incrementan su síntesis, el HIF-1α se transloca al núcleo, donde, unido al HIF-1β, actúa como factor transcripcional de genes con elementos de respuesta hipóxica (HRE) en su promotor. Estos regulan lasíntesis de una amplia serie de proteínas, que abarcan desde enzimas respiratorias y transportadores hasta hormonas involucradas en la regulación a escala del organismo de la circulación y la eritropoyesis. El papel del HIF-1 no se restringe a la mera inducción de una respuesta adaptativa a la falta de oxígeno, sino que participa significativamente en los mecanismos de reparación celular. Una simple lista de algunas alteraciones de importância fisiopatológica, tanto estimulatorias como inhibitorias, que involucran al sistema de HIF-1, incluiría: enfermedad pulmonar crónica, adaptación al tabaco/humo, anemia/hemorragia, isquemia/reperfusión, crecimiento, vascularización y resistencia celular de los tumores, preeclampsia y crecimiento intrauterino retardado, hiper o hipovascularización retiniana, sobredosis de fármacos, enfermedad inflamatoria intestinal y curación de heridas. Esta sola enumeración ilustra la importancia de este mecanismo. .

New, critically important data have been recently generated about the response to hypoxia. This response can be schematized in three main systems or functions, ie, detectional or oxygen sensing, regulatory, which controls gene expression and effector. The principal organizer of the regulatory branch is a specific transcription factor, the hypoxia-inducible factor 1 (HIF-1). In the presence of oxygen, the α subunit of HIF-1 (HIF-1α) is modified by hydroxylases, that represent the central point of the oxygen sensing mechanism. This type of hydroxylation induces HIF-1α catabolism by the proteosome. On the contrary, in hypoxia, or in the presence of certain growth factors that increase HIF-1α synthesis, HIF-1α translocates to the nucleus, where it binds HIF-1β, and thence acts on transcription of genes carrying hypoxia responsive elements (HRE) on their promoters. These genes regulate the synthesis of an ample series of proteins, which span from respiratory enzymes and transporters to hormones regulating circulation and erythropoiesis. The role of HIF-1α is not restricted to the mere induction of adaptation to decreased oxygen: instead, it significantly participates in cell repairing mechanisms. A simple list of some of the stimulatory or inhibitory alterations of pathophysiological importance involving the HIF-1 system, would include: chronic lung disease, smoking adaptation, anemia/hemorrhage, ischemia/reperfusion, growth, vascularization and cell resistance of tumors, preeclampsia and intrauterine growth retardation, retinal hyper ohypovascularization, drug intoxications, bowel inflammatory disease and wound repair. This list illustrates by itself the importance of the mechanism herein reviewed.