RESUMO
Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Proteínas de Membrana Transportadoras/genética , Neoplasias da Bexiga Urinária/genética , População Branca/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 18/genética , Progressão da Doença , Feminino , Loci Gênicos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Fatores de Risco , Adulto Jovem , Transportadores de UreiaRESUMO
Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
Assuntos
Cromossomos Humanos Par 4 , Predisposição Genética para Doença , Variação Genética , Neoplasias da Bexiga Urinária/genética , Alelos , Intervalo Livre de Doença , Europa (Continente) , Feminino , Genótipo , Humanos , Masculino , Modelos Genéticos , Mutação , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Recidiva , Risco , FumarRESUMO
OBJECTIVES: To report one case of renal cyst infected by Brucella, an exceptional pathology in our environment. METHODS: 82-year-old patient who was referred from his primary care physician for persistent microhematuria and piuria without evidence of infection. RESULTS: Radiological studies (XR+US+CTscan) showed a left renal cyst with parietal calcifications. Pathologic study was compatible with complicated cyst, with cultured (+) to Brucella spp. CONCLUSIONS: Renal involvement by Brucella is exceptional, and the cystic renal involvement is by far one of the more exceptional manifestations.
Assuntos
Brucella melitensis , Brucelose/complicações , Doenças Renais Císticas/microbiologia , Idoso de 80 Anos ou mais , Humanos , MasculinoRESUMO
Objetivos: Presentar un caso clínico de quiste renal infectado por Brucela, patología excepcional en nuestro medio. Método: Paciente de 82 años remitido desde Atención primaria por microhematuria y piuria persistentes sin evidencia de infección de orina. Resultado: El estudio radiológico (Rx+ECO+TAC) demuestra una imagen sugestiva de quiste renal izquierdo con calcificación depared. El estudio anatomopatológico se demostró compatible con quiste renal complicado y el cultivo fue positivo para Brucella spp. Conclusiones: La afectación renal por Brucela es excepcional, siendo aún más extraordinaria la infección de un quiste renal, motivo por el cual presentamos el caso (AU)
Objetives: To report one case of renal cyst infected by Brucella, an exceptional pathology in our environment. Methods: 82-year-old patient who was referred from his primary care physician for persistent microhematuria and piuria without evidence of infection. Results: Radiological studies (XR+US+CTscan) showed a left renal cyst with parietal calcifications. Pathologic study was compatible with complicated cyst, with cultured (+) to Brucella spp. Conclusions: Renal involvement by Brucella is exceptional, and the cystic renal involvement is by far one of the more exceptional manifestations (AU)
