RESUMEN
The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.
Asunto(s)
Biomarcadores de Tumor/genética , Citocromo P-450 CYP1A1/genética , Neoplasias de la Vesícula Biliar/etiología , Glutatión Transferasa/genética , Polimorfismo Genético/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Bolivia , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Vesícula Biliar/metabolismo , Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/patología , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Factores de RiesgoRESUMEN
Although genetic characteristics are considered to be a factor influencing the geographic variation in the prevalence of gallbladder cancer (GBC), they have not been well studied in Bolivia, which has a high prevalence rate of GBC. The purpose of this study was to examine the frequency of TP53 and K-ras mutations in Bolivian patients with GBC and to compare them with our previous data obtained in other high-GBC-prevalence countries, namely Japan, Chile, and Hungary. DNA was extracted from cancer sites in paraffin-embedded tissue from 36 patients using a microdissection technique. TP53 mutations at exons 5 to 8 and K-ras mutations at codons 12, 13 and 61 were examined using direct sequencing techniques. The data obtained were compared with those in the other high-GBC-prevalence countries. Of the 36 patients, 18 (50.0%) had a TP53 mutation (one mutation in each of 17 patients and three mutations in one patient), and only one (2.8%) had a K-ras mutation. Of the 20 TP53 mutations, 12 were of the transition type (60.0%). This rate was significantly lower than that in Chile (12/12, P<0.05). In addition, three mutations were of the CpG transition type (15.0%), which is a feature of endogenous mutation. All three were found in the hot spot region of the TP53 gene. In contrast, G:C to T:A transversion was found in Bolivia, suggesting the presence of exogenous carcinogens. Our findings suggest that the development of GBC in Bolivia is associated with both exogenous carcinogens and endogenous mechanisms. The identification of an environmental risk factor for GBC is needed to confirm these findings.
Asunto(s)
Neoplasias de la Vesícula Biliar/genética , Genes p53/genética , Genes ras/genética , Mutación/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Bolivia , Codón/genética , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
Introducción: El cáncer de cérvix es la causa más frecuente de muerte en la sierra central peruana. El tratamiento quirúrgico (histerectomía total laparoscópica e histerectomía radical más linfadenectomía pélvica laparoscópica) es el recurso terapéutico mayormente curativo en los estadios iníciales (Ia1, Ia2 y Ib1). Hace un año en el Servicio de Ginecología del Hospital IV Huancayo iniciamos el tratamiento quirúrgico laparoscópico en estos estadios. Objetivos: Revisar los resultados de histerectomía laparoscópica en cáncer microinvasivo de cuello uterino. Diseño: Estudio retrospectivo. Institución: Servicio de Ginecología, Hospital IV Huancayo, EsSalud, Junín, Perú. Pacientes: Doce mujeres sometidas a histerectomía laparoscópica por carcinoma microinvasivo de cérvix. Intervenciones: En seis mujeres con diagnóstico preoperatorio de cáncer de cérvix por conización cervical y estadio clínico Ia1 se les realizó histerectomía laparoscópica, con un tiempo operatorio de 59,16 minutos y tiempo de estancia hospitalaria de 4,1 días. A otras seis mujeres con estadio clínico Ia2-Ib1 se les realizó histerectomía radical más linfadenectomía pélvica laparoscópica, con un tiempo operatorio de 3 horas 58 minutos y tiempo de estancia hospitalaria de 10,1 días. Principales medidas de resultados: Curación clínica. Resultados: Todos los diagnósticos fueron confirmados con la pieza operatoria, y todas las pacientes estaban teóricamente curadas (márgenes libres, ganglios negativos); una paciente presentó complicaciones, requiriendo estancia prolongada (8,3%). Conclusiones: La histerectomía total laparoscópica y la histerectomía radical más linfadenectomía pélvica laparoscópica pueden ser realizadas de manera más rápida y radical con respecto a la histerectomía convencional por laparotomía. Ambas son intervenciones factibles y seguras, que pueden garantizar la curación en el carcinoma microinvasivo de cuello uterino.