RESUMO
CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias da Mama/tratamento farmacológico , Citocromo P-450 CYP2D6/genética , Tamoxifeno/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Idoso , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Polimorfismo Genético , Tamoxifeno/farmacocinética , Tamoxifeno/farmacologia , Fatores de TempoRESUMO
Premarital counseling is one of the most important strategies for prevention of genetic disorders, congenital anomalies and several medical, psychosocial marital problems. Nursing students as a target group are in a unique position to provide prospective couples with information and guidance regarding premarital counseling. The aim of this study is to assess knowledge and attitude of secondary technical nursing school students towards premarital counseling in Alexandria. The study was conducted at four secondary technical nursing schools. 200 students from the chosen schools participated in the study. Questionnaire sheet was developed to assess student's knowledge and a 3-point Likert-like scale was used to assess the student's attitude. The results revealed that 46.5% of the study sample had an average score in knowledge, while 65.5% of the students had a positive attitude towards premarital counseling. The recommendations focused on dissemination of information through formal and informal education and media publicity.
