RESUMEN
A multigenic model of prostate cancer susceptibility has been proposed, in which common polymorphic variants of genes, such as the androgen and vitamin D receptor, contribute to tumorigenesis. The discovery of additional genetic factors that contribute to prostate cancer risk should provide opportunities for new approaches to the detection and treatment of this common malignancy. Herein, we examined single nucleotide polymorphic variants in the 3'-untranslated region of CDKN1A (p21(cip1)) and in codon 109 of CDKN1B (p27(kip1)) for association with advanced prostate cancer in a European-American population. Ninety-six cases and 106 controls were analyzed using PCR amplification and restriction digestion assays. CDKN1A genotype was scored as CC, CT, and TT on the basis of the digestion products. The CDKN1A genotypes CT and TT were associated with an increased risk of advanced prostate carcinoma compared with the CC genotype [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.02-4.95]. The CDKN1B genotype was scored as VV, VG, or GG, again on the basis of the digestion products. The CDKN1B genotype VV was also associated with an increased risk of advanced prostate carcinoma (OR, 1.95; 95% CI, 1.09-3.47). These associations were particularly strong in those patients with androgen-independent disease [OR = 2.88 (95% CI, 1.19-6.97) and 2.11 (95% CI, 1.05-4.22) for high-risk genotypes of CDKN1A and CDKN1B, respectively]. In addition, the association of CDKN1B was particularly strong in the cohort of patients under the median age of diagnosis (OR, 2.23; 95% CI, 1.08-4.59). These results suggest that in a European-American population, CDKN1A and CDKN1B variants are associated with advanced prostate cancer. Analysis of CDKN1A and/or CDKN1B genotypes may prove useful in determining which patients are at risk for developing advanced prostate carcinoma and therefore would gain the most from aggressive screening, prophylaxis, and/or treatment.
Asunto(s)
Proteínas de Ciclo Celular/genética , Ciclinas/genética , Neoplasias de la Próstata/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
Rhesus monkey rhadinovirus (RRV) is a gamma2-herpesvirus identified from the peripheral blood mononuclear cells of rhesus macaques (Macaca mulatta). Serologic studies suggested that the infections of RRV are prevalent among rhesus monkeys. RRV can be efficiently propagated and grows to a high titer in cultured rhesus monkey fibroblasts, thus providing a valuable model to study the rhadinovirus replication. By comparative genomic studies, here we describe the identification of two potential transcriptional factors encoded by RRV, designated as R-Rta and R-bZIP. Initial functional characterization of these products suggested that R-Rta is a potent transcriptional activator and R-bZIP forms homodimers in vivo. Viral homologues of R-Rta and R-bZIP, previously identified from other rhadinoviruses, have been implicated in serving as molecular switches in lytic replication.