Subject(s)
Humans , Female , Pharmacogenetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Latin America , SurvivorshipABSTRACT
Las mujeres jóvenes (≤40 años) con cáncer de mama suelen tener un peor pronóstico que las mujeres posmenopáusicas, con repercusiones reproductivas y familiares importantes. El tratamiento quimioterapéutico, así como la hormonoterapia, pueden mejorar el pronóstico y la supervivencia libre de enfermedad (SLE); sin embargo, la capacidad individual de metabolizar los fármacos puede modificar la respuesta al tratamiento. Las diferencias interpersonales de esta capacidad tienen una explicación en las variaciones de los genes que codifican las enzimas que metabolizan los quimioterapéuticos y las hormonas endógenas y exógenas. Los genes del citocromo P450 (CYP450), CYP3A4, CYP2B6, CYP2D6 y CYP2C19, están involucrados en el metabolismo de los estrógenos y la ciclofosfamida, los taxanos y el tamoxifeno. La presente revisión expone la evidencia científica del efecto de los polimorfismos funcionales de estos genes sobre la SLE, y sus implicaciones, en las mujeres jóvenes con cáncer de mama. (AU)
Breast cancer prognosis tends to be worse in young women (≤40 years) than in postmenopausal women, with significant reproductive and family repercussions. Both chemotherapy and hormonal therapy can improve prognosis and disease-free survival but treatment response may be influenced by the individual's ability to metabolize drugs. Individual differences in metabolic ability can be explained by variations in the genes encoding the enzymes that metabolize chemotherapeutic agents and hormones. The cytochrome P450 genes CYP3A4, CYP2B6, CYP2D6 and CYP2C19 are involved in the metabolism of estrogen, cyclophosphamide, taxanes, and tamoxifen. This review discusses the scientific evidence of the effect of functional polymorphisms in these genes on disease-free survival and overall survival and its implications for young women with breast cancer. (AU)
Subject(s)
Humans , Female , Young Adult , Adult , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Pharmacogenetics , Survival , Cytochrome P-450 Enzyme SystemABSTRACT
Breast cancer (BC) is one of the most frequent cancer types in women worldwide. About 7% is diagnosed in young women (YBC) less than 40 years old. In Mexico, however, YBC reaches 15% suggesting a higher genetic susceptibility. There have been some reports of germline variants in YBC across the world. However, there is only one report from a Mexican population, which is not restricted by age and limited to a panel of 143 genes resulting in 15% of patients carrying putatively pathogenic variants. Nevertheless, expanding the analysis to whole exome involves using more complex tools to determine which genes and variants could be pathogenic. We used germline whole exome sequencing combined with the PeCanPie tool to analyze exome variants in 115 YBC patients. Our results showed that we were able to identify 49 high likely pathogenic variants involving 40 genes on 34% of patients. We noted many genes already reported in BC and YBC worldwide, such as BRCA1, BRCA2, ATM, CHEK2, PALB2, and POLQ, but also others not commonly reported in YBC in Latin America, such as CLTCL1, DDX3X, ERCC6, FANCE, and NFKBIE. We show further supporting and controversial evidence for some of these genes. We conclude that exome sequencing combined with robust annotation tools and further analysis, can identify more genes and more patients affected by germline mutations in cancer.
ABSTRACT
Introducción: Los médicos de familia juegan un papel fundamental en la promoción de las prácticas adecuadas de la lactancia materna (LM), por lo que deben tener un conocimiento adecuado sobre el tema.ObjetivoEvaluar el conocimiento sobre la LM y los factores asociados en los médicos de familia en una unidad de primer nivel de atención de Cuernavaca, México.Material y métodosSe realizó un estudio transversal, en 93 médicos adscritos y residentes de medicina de familia. El conocimiento sobre la LM se evaluó mediante el cuestionario ECoLa de 20 ítems, considerando variables familiares y demográficas. Se realizó una estadística descriptiva de los datos y los factores asociados al nivel de conocimiento se evaluaron mediante un modelo de regresión logística.ResultadosDe la muestra, el 72% fueron mujeres; 41% estaban casados y 55% tenían al menos un hijo, el 23% había tomado al menos un curso de LM. Se obtuvo una media de 11,5 aciertos en el cuestionario ECoLa, 52% se clasificaron en un nivel de conocimiento bajo, 45% en regular y 3% en adecuado. Después del ajuste por edad, cursos de lactancia y estado civil, las principales variables asociadas a un conocimiento regular/bueno fueron tener al menos un hijo (OR 4,63 IC 95% 1,1-19,42) y el sexo (mujer OR 5,75 IC 95% 1,58-20,94).ConclusionesEl 52% de los médicos de familia mostró un conocimiento bajo sobre la LM. La experiencia personal de la paternidad o maternidad de los médicos de familia se asocia al mejor conocimiento de la LM, superando a las capacitaciones y a los cursos. (AU)
Introduction: The Family doctors play a fundamental role in promoting an adequate breastfeeding practices, so they must have an adequate knowledge of this matters.ObjectiveEvaluate the knowledge about breastfeeding in family doctors of a first level care unit in Cuernavaca, Mexico.Material and methodsThe study was cross-sectional with 93 Family doctors and family medicine residents. The knowledge about breastfeeding was evaluated using the ECoLa questionnaire of 20 items, considering family and demographic variables. Were performed descriptive statistics and the factors associated with the level of knowledge were evaluated using a logistic regression model.ResultsFrom the sample 72% were women, 41% were married and 55% had at least one child, 23% had taken at least one breastfeeding course. On average 11.5 hits out in ECoLa questionnaire, 52% were classified as low knowledge level, 45% as regular and 3% as good. After adjustment for age, lactation courses, and marital status. The main variables associate to knowledge regular / good were had at least one child, (OR 4.63 95% CI 1.1-19.42), and sex (woman OR 5.75 95% CI 1.58-20.94).Conclusions52% of family doctors showed low knowledge about breastfeeding. The personal experience of paternity or maternity of family doctors is a relevant factor associated with better knowledge of exclusive breastfeeding, surpassing training and courses. (AU)
