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Cancer Res Treat ; 51(3): 1180-1187, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30590007

RESUMO

PURPOSE: To establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival. MATERIALS AND METHODS: Five thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q). RESULTS: The NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004). CONCLUSION: The NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q).


Assuntos
Proteínas de Ciclo Celular/genética , Mutação em Linhagem Germinativa , Proteínas Nucleares/genética , Neoplasias da Próstata/mortalidade , Deleção de Sequência , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Razão de Chances , Prognóstico , Neoplasias da Próstata/genética , Análise de Sobrevida
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