Association Study Among Candidate Genetic Polymorphisms and Chemotherapy-Related Severe Toxicity in Testicular Cancer Patients

Testicular cancer is one of the most commonly occurring malignant tumors in young men with fourfold higher rate of incidence and threefold higher mortality rates in Chile than the average global rates. Surgery is the initial line of treatment for testicular cancers, and is generally followed by chemotherapy, usually with combinations of bleomycin, etoposide, and cisplatin (BEP). However, the adverse effects of chemotherapy vary significantly among individuals; therefore, the present study explored the association of functionally significant allelic variations in genes related to the pharmacokinetics/pharmacodynamics of BEP and DNA repair enzymes with chemotherapy-induced toxicity in BEP-treated testicular cancer patients. We prospectively recruited 119 patients diagnosed with testicular cancer from 2010 to 2017. Genetic polymorphisms were analyzed using PCR and/or qPCR with TaqMan®probes. Toxicity was evaluated based on the Common Terminology Criteria for Adverse Events, v4.03. After univariate analyses to define more relevant genetic variants (p < 0.2) and clinical conditions in relation to severe (III–IV) adverse drug reactions (ADRs), stepwise forward multivariate logistic regression analyses were performed. As expected, the main severe ADRs associated with the non-genetic variables were hematological (neutropenia and leukopenia). Univariate statistical analyses revealed that patients with ERCC2 rs13181 T/G and/or CYP3A4 rs2740574 A/G genotypes are more likely to develop alopecia; patients with ERCC2 rs238406 C/C genotype may develop leukopenia, and patients with GSTT1-null genotype could develop lymphocytopenia (III–IV). Patients with ERCC2 rs1799793 A/A were at risk of developing severe anemia. The BLMH rs1050565 G/G genotype was found to be associated with pain, and the GSTP1 G/G genotype was linked infection (p < 0.05). Multivariate analysis showed an association between specific ERCC1/2 genotypes and cumulative dose of BEP drugs with the appearance of severe leukopenia and/or febrile neutropenia. Grades III–IV vomiting, nausea, and alopecia could be partly explained by the presence of specific ERCC1/2, MDR1, GSTP1, and BLMH genotypes (p < 0.05). Hence, we provide evidence for the usefulness of pharmacogenetics as a tool for predicting severe ADRs in testicular cancer patients treated with BEP chemotherapy

Association study among candidate genetic polymorphisms and chemotherapy-related severe toxicity in testicular cancer patients

Testicular cancer is one of the most commonly occurring malignant tumors in young men with fourfold higher rate of incidence and threefold higher mortality rates in Chile than the average global rates. Surgery is the initial line of treatment for testicular cancers, and is generally followed by chemotherapy, usually with combinations of bleomycin, etoposide, and cisplatin (BEP). However, the adverse effects of chemotherapy vary significantly among individuals; therefore, the present study explored the association of functionally significant allelic variations in genes related to the pharmacokinetics/pharmacodynamics of BEP and DNA repair enzymes with chemotherapy-induced toxicity in BEP-treated testicular cancer patients. We prospectively recruited 119 patients diagnosed with testicular cancer from 2010 to 2017. Genetic polymorphisms were analyzed using PCR and/or qPCR with TaqMan®probes. Toxicity was evaluated based on the Common Terminology Criteria for Adverse Events, v4.03. After univariate analyses to define more relevant genetic variants (p < 0.2) and clinical conditions in relation to severe (III-IV) adverse drug reactions (ADRs), stepwise forward multivariate logistic regression analyses were performed. As expected, the main severe ADRs associated with the non-genetic variables were hematological (neutropenia and leukopenia). Univariate statistical analyses revealed that patients with ERCC2 rs13181 T/G and/or CYP3A4 rs2740574 A/G genotypes are more likely to develop alopecia; patients with ERCC2 rs238406 C/C genotype may develop leukopenia, and patients with GSTT1-null genotype could develop lymphocytopenia (III-IV). Patients with ERCC2 rs1799793 A/A were at risk of developing severe anemia. The BLMH rs1050565 G/G genotype was found to be associated with pain, and the GSTP1 G/G genotype was linked infection (p < 0.05). Multivariate analysis showed an association between specific ERCC1/2 genotypes and cumulative dose of BEP drugs with the appearance of severe leukopenia and/or febrile neutropenia. Grades III-IV vomiting, nausea, and alopecia could be partly explained by the presence of specific ERCC1/2, MDR1, GSTP1, and BLMH genotypes (p < 0.05). Hence, we provide evidence for the usefulness of pharmacogenetics as a tool for predicting severe ADRs in testicular cancer patients treated with BEP chemotherapy

En el iris de los in-visibles: una mirada al bienestar psicológico, calidad de vida y apoyo social de población víctima del conflicto armado

Esta obra ofrece elementos conceptuales y de reflexión sobre la posibilidad efectiva de reparar a los sobrevivientes del conflicto armado, por las connotaciones jurídicas y psicosociales del término y el alcance real de la Ley de Víctimas y Restitución de Tierras. El libro toma como base los resultados y la experiencia obtenidos en la investigación Bienestar psicológico, calidad de vida y apoyo social de población víctima del conflicto armado en Colombia, estudio descriptivo, de corte transversal, orientado a establecer la relación entre el bienestar psicológico, la calidad de vida y el apoyo social percibido de la población víctima del conflicto armado en Bello, Trujillo, Montería, Santa Marta y Barrancabermeja, y que fue beneficiada con alguna medida de atención, asistencia y reparación de la ley mencionada. Se aplicaron tres instrumentos (whoqol-bref y mos, de apoyo social percibido, y la escala de bienestar psicológico de Ryff) a un total de 1139 personas (muestreo no probabilístico) reconocidas por el Estado como víctimas y beneficiadas con alguna medida de la mencionada ley. Los resultados muestran que hay una asociación entre el bienestar psicológico y la recepción de la medida “atención” de ley. La calidad de vida y el apoyo social percibido por la población participante se asocian con haber recibido alguna de las medidas de atención, asistencia y reparación. Los últimos dos capítulos presentan dos lecturas de realidades que complementan lo abordado en el estudio: las experiencias en Trujillo, Valle y Montería, cuyos resultados coinciden con los hallazgos generales del estudio, de acuerdo con un enfoque territorial e individual.This work offers conceptual elements and reflection on the effective possibility of repairing the survivors of the armed conflict, by the legal and psychosocial connotations of the term and the real scope of the Victims and Land Restitution Law. The book is based on the results and experience obtained in the research Psychological well-being, quality of life and social support of the population victim of the armed conflict in Colombia, a descriptive, cross-sectional study aimed at establishing the relationship between psychological well-being, quality of life and the perceived social support of the population victim of the armed conflict in Bello, Trujillo, Montería, Santa Marta and Barrancabermeja, and that was benefited with some measure of attention, assistance and reparation of the aforementioned law. Three instruments (whoqol-bref and mos, of perceived social support, and Ryff’s psychological well-being scale) were applied to a total of 1139 people (non-probabilistic sampling) recognized by the State as victims and benefited with some measure of the law. The results show that there is an association between psychological well-being and the reception of the “attention” measure of the law. The quality of life and social support perceived by the participating population are associated with having received some of the care, assistance and repair measures. The last two chapters present two readings of realities that complement what was addressed in the study: the experiences in Trujillo, Valle and Montería, whose results coincide with the general findings of the study, according to a territorial and individual approach.Presentación. -- Prólogo. -- Introducción. -- Algunas premisas y antecedentes sobre el conflicto. -- El ser. -- La víctima y la atención estatal. -- Visibilizar lo invisible: quiénes y cómo somos víctimas. -- El rol de las víctimas en la sociedad del posacuerdo: un acercamiento conceptual desde lo social. -- Lo psicológico, lo político y lo legal. -- Bienestar psicológico. -- Calidad de vida y apoyo social percibido en personas cobijadas por la Ley 1448 del 2011. -- El caso Trujillo. Una experiencia desde lo rural. -- Calidad de vida en personas víctimas del conflicto armado: caso Córdoba (Colombia). -- Referencias. -- Sobre los autoreshttps://scienti.colciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001437398https://orcid.org/0000-0003-1458-6770https://scienti.colciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000004810wilson.salas@campusucc.edu.cohttps://scholar.google.com/citations?user=5m4ZUTUAAAAJ&hl=e

En el iris de los in-visibles: una mirada al bienestar psicológico, calidad de vida y apoyo social de población víctima del conflicto armado

Esta obra ofrece elementos conceptuales y de reflexión sobre la posibilidad efectiva de reparar a los sobrevivientes del conflicto armado, por las connotaciones jurídicas y psicosociales del término y el alcance real de la Ley de Víctimas y Restitución de Tierras. El libro toma como base los resultados y la experiencia obtenidos en la investigación Bienestar psicológico, calidad de vida y apoyo social de población víctima del conflicto armado en Colombia, estudio descriptivo, de corte transversal, orientado a establecer la relación entre el bienestar psicológico, la calidad de vida y el apoyo social percibido de la población víctima del conflicto armado en Bello, Trujillo, Montería, Santa Marta y Barrancabermeja, y que fue beneficiada con alguna medida de atención, asistencia y reparación de la ley mencionada. Se aplicaron tres instrumentos (whoqol-bref y mos, de apoyo social percibido, y la escala de bienestar psicológico de Ryff) a un total de 1139 personas (muestreo no probabilístico) reconocidas por el Estado como víctimas y beneficiadas con alguna medida de la mencionada ley. Los resultados muestran que hay una asociación entre el bienestar psicológico y la recepción de la medida “atención” de ley. La calidad de vida y el apoyo social percibido por la población participante se asocian con haber recibido alguna de las medidas de atención, asistencia y reparación. Los últimos dos capítulos presentan dos lecturas de realidades que complementan lo abordado en el estudio: las experiencias en Trujillo, Valle y Montería, cuyos resultados coinciden con los hallazgos generales del estudio, de acuerdo con un enfoque territorial e individual.This work offers conceptual elements and reflection on the effective possibi- lity of repairing the survivors of the armed conflict, by the legal and psychosocial connotations of the term and the real scope of the Victims and Land Restitution Law. The book is based on the results and experience obtained in the research Psychological well-being, quality of life and social support of the population victim of the armed conflict in Colombia, a descriptive, cross-sectional study aimed at establishing the relationship between psychological well-being, quality of life and the perceived social support of the population victim of the armed conflict in Bello, Trujillo, Montería, Santa Marta and Barrancabermeja, and that was benefited with some measure of attention, assistance and reparation of the aforementioned law. Three instruments (whoqol-bref and mos, of perceived social support, and Ryff’s psychological well-being scale) were applied to a total of 1139 people (non-probabi- listic sampling) recognized by the State as victims and benefited with some measure of the law. The results show that there is an association between psychological well-being and the reception of the “attention” measure of the law. The quality of life and social support perceived by the participating population are associated with having received some of the care, assistance and repair measures. The last two chapters present two readings of realities that complement what was addressed in the study: the experiences in Trujillo, Valle and Montería, whose results coincide with the general findings of the study, according to a territorial and individual approach.1. Algunas premisas y antecedentes sobre el conflicto, el ser, la víctima y la atención estatal -- 2. Visibilizar lo invisible: quiénes y cómo somos víctimas -- 3. El rol de las víctimas en la sociedad del posacuerdo: un acercamiento conceptual desde lo social, lo psicológico, lo político y lo legal -- 4. Bienestar psicológico, calidad de vida y apoyo social percibido en personas cobijadas por la Ley 1448 del 2011 -- 5. El caso Trujillo. Una experiencia desde lo rural -- 6. Calidad de vida en personas víctimas del conflicto armado: caso Córdoba (Colombia) -- 7. Referencias. -- 8. Sobre los autores