RESUMEN
Base excision repair (BER) plays an important role in maintaining genome integrity and anti-cancer drug resistance. Single nu-cleotide polymorphisms (SNPs) in BER genes were detected in 500 lung cancer patients and 500 cancer-free controls. A logistic regression model was applied to analyze the relationship between lung cancer susceptibility and BER SNPs coupled with a wide range of epidemiological factors in a Chinese population. SNPs including rs25487 in the X-ray repair cross-complementing group 1 gene, rs1052133 in the 8-oxoguanine DNA gly-cosylase gene, and rs1136410 in the poly (ADP-ribose) polymerase 1 gene were identified. Multivariate analysis showed that the rs25487-AG geno-type was associated with a higher incidence of lung cancer compared with the GG genotype. The rs25487 SNP was associated with the pathological distribution of lung cancer. Moreover, rs1052133-GG was associated with early age of lung cancer onset compared with the CC genotype. Our data demonstrated that the SNPs rs25487 and rs1052133 are risk factors for lung cancer in epidemiologically susceptible Chinese people.
Asunto(s)
Pueblo Asiatico/genética , Proteínas de Unión al ADN/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , China/epidemiología , Comorbilidad , ADN Glicosilasas/genética , Femenino , Genotipo , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/genética , Factores de Riesgo , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X , Adulto JovenRESUMEN
Fas/FasL protein expression of bone marrow hematopoietic cells was investigated in severe aplastic anemia (SAA) patients. Fas expression was evaluated in CD34(+), GlycoA(+), CD33(+), and CD14(+) cells labeled with monoclonal antibodies in newly diagnosed and remission SAA patients along with normal controls. FasL expression was evaluated in CD8(+) cells in the same manner. In CD34(+) cells, Fas expression was significantly higher in the newly diagnosed SAA group (46.59 ± 27.60%) than the remission (6.12 ± 3.35%; P < 0.01) and control (8.89 ± 7.28%; P < 0.01) groups. In CD14(+), CD33(+), and GlycoA(+) cells, Fas levels were significantly lower in the newly diagnosed SAA group (29.29 ± 9.23, 46.88 ± 14.30, and 15.15 ± 9.26%, respectively) than in the remission (47.23 ± 31.56, 67.22 ± 34.68, and 43.56 ± 26.85%, respectively; P < 0.05) and normal control (51.25 ± 38.36, 72.06 ± 39.88, 50.38 ± 39.88%, respectively; P < 0.05) groups. FasL expression of CD8(+) cells was significantly higher in the newly diagnosed SAA group (89.53 ± 45.68%) than the remission (56.39 ± 27.94%; P < 0.01) and control (48.63 ± 27.38%; P <0.01) groups. No significant differences were observed between the remission and control groups. FasL expression in CD8(+) T cells was significantly higher in newly diagnosed patients, and CD34(+), CD33(+), CD14(+), and GlycoA(+) cells all showed Fas antigen expression. The Fas/FasL pathway might play an important role in excessive hematopoietic cell apoptosis in SAA bone marrow. Furthermore, CD34(+) cells are likely the main targets of SAA immune injury.