RESUMEN
Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women's risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80-0.88) and 0.81 (95% CI: 0.76-0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.
Asunto(s)
Neoplasias de la Mama/genética , Metilación de ADN , Epigenómica/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mama/citología , Mama/metabolismo , Neoplasias de la Mama/metabolismo , Cuello del Útero/citología , Cuello del Útero/metabolismo , Islas de CpG , Epigenoma , Células Epiteliales/metabolismo , Femenino , Humanos , Mutación , Pronóstico , Curva ROCRESUMEN
INTRODUCTION: This study investigates the efficiency of teaching basic surgical skills to foundation-year doctors and medical students by using local resources. METHODS: A course comprising 4 workshops, once a week, of 3 hours duration per session was delivered using local education center facilities and using the local faculty of consultants and surgical trainees. Teaching methods include practical skill stations supplemented with short didactic lectures and group discussion. Precourse and postcourse assessments were completed by candidates and analyzed to measure outcomes of the course both subjectively and objectively. RESULTS: A total number of 20 participants completed the course. On completion of the course, (1) participants' theoretical knowledge improved significantly (p < 0.0001), as measured by multiple-choice questions, and scores improved by 35% (mean 44%, standard deviation = 16%) before the course compared to (mean = 79%, standard deviation = 13) after the course; (2) the level of confidence in knowledge and skills was measured by a questionnaire on a scale of 1 to 5, and there was a significant (p < 0.0001) improvement on postcourse assessment (mean difference = 1.5, 95% CI: 0.7-2.4); and (3) practical skills such as suture position, knot tying, and wound apposition significantly improved after the course, χ(2) (2) = 16, p < 0.001; χ(2) (2) = 18, p < 0.001; and χ(2) (2) = 22, p < 0.0001, respectively. CONCLUSION: Effective delivery of basic surgical skills to foundation-year doctors by using local resources can be achieved at low cost.