RESUMEN
BACKGROUND: DNA repair enzymes repair some of the DNA damage associated with risk factors for renal cell carcinoma (RCC), including smoking. DNA repair gene polymorphisms modulate the repair capacity and might influence individual risk and progression of RCC. We examined associations between functional polymorphisms and risk, clinicopathologic characteristics and survival of RCC. PATIENTS AND METHODS: The study groups comprised 215 RCC patients and 215 age- and gender-matched healthy controls. Polymorphisms in xeroderma pigmentosum complementation groups C, D and G and X-ray repair cross-complementing groups 1 and 3 genes were genotyped. RESULTS: No significant differences in DNA repair genotype were observed between RCC cases and controls. In all patients, however, greater numbers (> or =3) of total variant alleles in all DNA repair genes studied were associated with less frequent venous extension (P = 0.0079). In smokers, some genotypes were associated with characteristics of RCC (Ps < or = 0.0067) and smokers with greater numbers of total variant alleles had improved overall survival (P = 0.040). CONCLUSION: These results suggest that DNA repair gene polymorphisms may not influence RCC susceptibility, but that some of them may influence RCC progression, especially in smokers, possibly due to altered DNA repair capacity by these polymorphisms.
Asunto(s)
Carcinoma de Células Renales/genética , Reparación del ADN/genética , Predisposición Genética a la Enfermedad/epidemiología , Neoplasias Renales/genética , Polimorfismo Genético , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Biopsia con Aguja , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Estudios de Casos y Controles , Intervalos de Confianza , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Genotipo , Humanos , Inmunohistoquímica , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Probabilidad , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Análisis de SupervivenciaRESUMEN
DNA repair enzymes repair DNA damaged by platinum agents and ionising radiation. Single nucleotide polymorphisms (SNPs) in DNA repair genes modulate the repair capacity and might affect response and prognosis following platinum-based chemoradiotherapy (CRT). We investigated associations between the functional SNPs in DNA repair genes and response and survival in muscle-invasive bladder cancer patients treated with CRT to determine the predictive value of the SNPs in patient selection for bladder conservation therapy. The study group comprised 78 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms in xeroderma pigmentosum complementation groups C (Lys939Gln, A/C), D (XPD; Lys751Gln, A/C), and G (Asp1104His, G/C), and X-ray repair cross-complementing groups 1 (XRCC1; Arg399Gln, G/A) and 3 (Thr241Met, T/C) genes were genotyped. Combined genotypes with at least one variant allele in XPD or XRCC1 were significantly associated with improved cancer-specific survival compared with remaining groups (P=0.009). In multivariate analysis, only the combined XPD and XRCC1 genotypes were independently associated with cancer-specific survival (P=0.04). The association was stronger in stage T3/T4 patients (P=0.0008). These results suggest that combined XPD and XRCC1 genotypes might be prognostic factors in muscle-invasive bladder cancer patients treated with CRT.
Asunto(s)
Reparación del ADN/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/radioterapia , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Terapia Combinada , Esquema de Medicación , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso/patología , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Recurrencia , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidad , Proteína de la Xerodermia Pigmentosa del Grupo D/genéticaRESUMEN
A case of neuroendocrine carcinoma (small cell carcinoma) of the urinary bladder is presented. A 76-year-old man complaining of dysuria visited our clinic on October 31, 1997. On physical examination, a huge mass was palpable in the lower abdomen. Abdominal and pelvic computed tomographic (CT) scan revealed a huge mass, 6.7 x 6.0 cm in size, with extravesical extension in the anterior wall of the urinary bladder and no metastatic lesions. Percutaneous biopsy of the tumor revealed undifferentiated neuroendocrine carcinoma. The value of serum neuron specific enolase (NSE) was 220 ng/ml (normal range: 0-10 ng/ml). Twenty days after the first CT scan, the tumor had grown to be 12.5 x 11.0 cm in size. He was treated with combination therapy of systemic cisplatin and external pelvic radiation and then achieved complete remission on CT scan and biopsy. The value of serum NSE was normalized. Four months later, abdominal CT scan revealed a huge metastastic lesion in the paraaortic and parahepatic regions, but, no local recurrence in the bladder. The value of serum NSE was 240 ng/ml. He was treated with 4 cycles of systemic combination therapy of cisplatin and etoposide. He achieved partial remission (regression rate: 77%) on CT scan after completion of the first 2 cycles, but the tumor showed rapid re-growth and he died of cancer 1 month later despite another 2 cycles. These combination therapies were effective against neuroendocrine carcinoma of the urinary bladder, although, the duration of the effect was short.