RESUMEN
There were analyzed associating of functional polymorphism of the promoter regions of genes MMP2 C--1306T, MMP 9 C--1562 T, MMP3 5A--1171 6A in a group of healthy women and breast cancer patients in order to identify informative markers associated with the risk of developing the disease. The study included 395 DNA samples from women with breast cancer and 329 healthy women. Genotyping of polymorphisms was carried out by restriction analysis of amplification products (RFLP-analysis). Among female patients there was revealed significantly seldom a carrier of 6A6A MMP3-1117 and MMP 9-1562TT genotypes and also significantly increased the frequency of MMP3 5A6A genotype. The risk of lymph node metastasis reduced in patients with MMP9-1562CC genotype. Conversely heterozygosis at this position could be regarded as risk factor for metastasis. It was revealed associating of MMP3 5A6A genotype with the degree of malignancy.
Asunto(s)
Neoplasias de la Mama/enzimología , Neoplasias de la Mama/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Neoplasias de la Mama/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Federación de RusiaRESUMEN
Previously, we showed the association of neoadjuvant chemotherapy (NAC) response with changing the expression vector (increase or decrease) of multidrug resistance genes (MDR) in breast tumors during chemotherapy. The aim of the present study was to evaluate the relation between changes in the expression vector of MDR genes and distant metastasis-free survival. Patients (n = 120) with breast cancer (T1-4N0-3M0) treated by 2-4 cycles of NAC (CAX, FAC, and taxane regimes) and 4 cycles of adjuvant chemotherapy (FAC) were included. TaqMan-based quantitative reverse transcriptase PCR (qRT-PCR) was used to estimate the expression of the following MDR genes: ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2, GSTP1, and MVP--in biopsies before NAC and in tumor samples after chemotherapy. Comparing the corresponding expression levels allowed us to identify the vector of expression change during NAC. The results showed that 5-year distant metastasis-free survival was 73-78% in patients with a decrease in ABCB1, ABCC2, and ABCG1 expression. The up-regulation of these genes during NAC was related to a significant decrease (up to 50-55%) in metastasis-free survival (Kaplan-Meier analysis: log-rank p value = 0.006-0.03). The association of changing the expression vector of MDR genes with metastasis-free survival did not depend on tumor size, lymph node involvement, histological form, receptor status, molecular subtype, and others clinicopathological parameters of breast cancer. The obtained data suggest that changing the expression vector of MDR genes in breast tumors during NAC may be used as a new potential prognostic marker of breast cancer. An increase in tumor expression of ABCB1, ABCC2, and ABCG1 during chemotherapy is a factor of poor prognosis, whereas down-regulation of these genes--a favorable prognostic marker.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Terapia Neoadyuvante/métodos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Regulación hacia Abajo , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Regulación hacia ArribaRESUMEN
Analyzed the association of functional polymorphisms of VEGFA at positions -2578 of promoter region and at position +936 3' of untranslated region in a group of healthy women and breast cancer patients with the aim to detect informative markers associated with the risk of disease. The study included 395 DNA samples from women with breast cancer and 298 healthy women. Genotyping of polymorphisms of C-2578A and C +936 T VEGFA was performed by restrictase analysis of amplification products (RFLP-analysis). There was revealed the increase of the frequency-2578AA genotype in patients with breast cancer (OR 1.55, 95% CI 1,55-2,29), moreover, the frequency of this genotype increased in the group of patients with a common family history and with breast cancer in close relatives of relatively healthy women (OR = 2,03 95% CI 1,26-3,27 and OR = 2,22 95% CI 1,13-4,33, respectively). Genotype frequencies of -2578AA/+ 936 SS and -2578SS/+ 936 CT were significantly higher in the group of patients with a factor of family history as compared to the group of patients without it (OR = 1,84 95% CI 1,01-3,34 and OR = 2,91 95% CI 1,09-8,05 respectively).
Asunto(s)
Neoplasias de la Mama/genética , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , Secuencias Reguladoras de Ácidos Nucleicos/genética , Factores de RiesgoRESUMEN
All complications diagnosed at early stages of breast cancer were associated with small tumors, especially with those arising in the aftermath of fibrocystic disease. Hence, our task was to study the XR-semiotics of lesions of less than 15 mm in diameter and of the same origin. 100 mammograms of breast cancer patients with benign disease of the breast were studied. The presence of moderate-to-severe fibrocystic disease significantly affected the visualization of lesions of less than 10 mm in diameter. Since the XR-semiotics of small tumors failed to reveal malignancy features, all lesions visualized by mammography required additional diagnostic procedures using ultrasound and invasive radiology.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Enfermedad Fibroquística de la Mama/complicaciones , Mamografía , Adulto , Neoplasias de la Mama/etiología , Transformación Celular Neoplásica/patología , Femenino , Enfermedad Fibroquística de la Mama/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Radiografía Intervencional , Ultrasonografía MamariaRESUMEN
This study involved 525 breast cancer (BC) patients of T2-4N0-2M0 stages at the age of 35 years and older. Significant differences in clinical and pathological characteristics between premenopausal and postmenopausal BC patients were found. Mostly marked differences were shown for positive lymph node correlation with distant metastasis, multicentric growth and local recurrence depending on menopause status. The prevalence of various morphological structures in primary tumors was appeared to be associated with different forms of tumor progression in pre- and postmenopausal women. We have studied polymorphisms in 15 genes involved in major cancer related pathways (apoptosis, interleukins, folate metabolism enzymes genes). We found that variant genotypes of MTHFR and DHFR genes were associated with an increased BC risk among premenopausal women while polymorphism in IL-18, p53 genes were associated with BC among postmenopausal women. These results demonstrate novel biological information, which points the different mechanisms contributed to breast cancer progression in premenopausal and postmenopausal women.