RESUMEN
A case of a 13 year old girl who manifested hyperprolactinaemia and galactorrhea induced by Omeprazole, a commonly used proton pump inhibitor is presented.
Asunto(s)
Galactorrea/inducido químicamente , Hiperprolactinemia/inducido químicamente , Omeprazol/efectos adversos , Inhibidores de la Bomba de Protones , Adolescente , Antiulcerosos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Humanos , Omeprazol/uso terapéutico , Resultado del TratamientoRESUMEN
Case of a seventy year old female, who developed cerebral salt wasting syndrome in association with Tuberculous Meningitis is presented.
Asunto(s)
Hiponatremia/diagnóstico , Mycobacterium/aislamiento & purificación , Cloruro de Sodio/orina , Tuberculosis Meníngea/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Anciano , Antituberculosos/administración & dosificación , Líquido Cefalorraquídeo/fisiología , Femenino , Fludrocortisona/administración & dosificación , Humanos , Hiponatremia/complicaciones , Hiponatremia/tratamiento farmacológico , Síndrome , Resultado del Tratamiento , Tuberculosis Meníngea/complicaciones , Tuberculosis Meníngea/tratamiento farmacológico , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
BACKGROUND: Majority of the BRCA1 and BRCA2 mutations are associated with the risk of sporadic and familial breast cancer. Since these genes are significant in DNA repair mechanisms, we focused homology-directed DNA repair (HDDR) and BRCA complex. METHODS: We selected BRCA1 variant (rs80356932, 4491C/T) and BRCA2 variant (rs80359182, 319T/C) from the interaction region of BRCA complex and studied in 100 breast cancer patients and 100 controls using tetra-ARMS-PCR. RESULTS: Here we show that BRCA1 and BRCA2 variants are significantly associated with high breast cancer risk (BRCA1 rs80356932; Genotype T/T OR 8.66, 95% CI 3.16-23.71, p < 0.0001; Allele-T, OR 2.48, 95% CI 1.62-3.81, p < 0.0001 and BRCA2 rs80359182; Genotype C/C OR 4.32, 95% CI 1.95-9.53, p = 0.0001; Allele-C, OR 2.19, 95% CI 1.43-3.34, p = 0.0002). Additionally, bioinformatics analysis showed that BRCA2-tryptophan > arginine substitutions result in altered interaction of BRCA1/PALB2/BRCA2/protein complex and impaired HDDR pathway. We also observed that breast cancer risk was significantly increased in over-weighted and obese women. CONCLUSIONS: Our results indicate that high risk of breast cancer is significantly associated with BRCA1 and BRCA2 variants, and mutations may alter the protein interactions of BRCA complex that results in tumor genesis.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad/genética , Adulto , Anciano , Proteína BRCA2/metabolismo , Proteína del Grupo de Complementación N de la Anemia de Fanconi/metabolismo , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Persona de Mediana Edad , Simulación del Acoplamiento Molecular , Mutación , Pakistán , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Variants of DNA repair genes are extensively reported to cause genetic instability and increase the risk of breast cancer. In combination with NBS1, MRE11 and RAD50 constitute an MRN (MRE11-RAD50-NBS1) complex that repairs DNA damage. However, certain genetic alterations in MRE11 and RAD50 produce abnormal protein that affects the repairing process and may result in malignancy. We aimed to investigate the association of MRE11 and RAD50 polymorphisms with breast risk in the female population of Punjab, Pakistan. METHODS: We collected blood samples of 100 breast cancer patients and 100 tumor-free females selected as controls. Extracted DNA was genotyped by tetra ARMS-PCR followed by gel electrophoresis. Results were analyzed by SPSS and SNPstats to analyze the association of different clinical factors and SNPs (single nucleotide polymorphisms) with the risk of breast cancer. RESULTS: We found that the increased risk of breast cancer is associated with MRE11 variant rs684507 (odds ratio-OR 3.71, 95% confidence interval-CI 1.68-8.18, p value < 0.0001), whereas, RAD50 variant rs28903089 appeared to have protective effect (OR 0.55, CI 0.29-1.02, p value = 0.003). Additionally, clinical factors such as positive family history, life style, and marital status also play significant roles in breast cancer development. CONCLUSION: In the present study, strong risk of breast cancer was associated with MRE11 gene. However, RAD50 showed protective effect. Additionally, clinical factors are also pivotal in risk assessment. We anticipate that targeting specific genetic variations confined to ethnic groups would be more effective in future therapeutic approaches for prevention and treatment of breast cancer.