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Sökning: WFRF:(Hemminki K) > Onelov E.

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1.
  • Berggren de Verdier, P. J., et al. (författare)
  • Prognostic significance of homozygous deletions and multiple duplications at the CDKN2A (p16INK4a)/ARF (p14ARF) locus in urinary bladder cancer
  • 2006
  • Ingår i: Scand J Urol Nephrol. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 40:5, s. 363-9
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The 9p21 locus is a major target in the pathogenesis of human urinary bladder cancer. This locus harbours the CDKN2A/ARF tumour suppressor gene, which encodes two cell-cycle regulatory proteins: p16INK4a and p14ARF. We studied how homozygous deletions and multiple duplications at this locus affect prognosis and survival in patients with bladder cancer. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (QPCR), based on simultaneous amplification of ARF and a reference gene, glyceraldehyde-3-phosphate dehydrogenase, was used to measure homozygous deletions and multiple duplications in a population-based material consisting of 478 patients with urinary bladder cancer. Results from real-time QPCR were compared with clinico-pathological parameters and survival curves were generated using the Kaplan-Meier method. RESULTS: Real-time QPCR analysis showed 71 (15%) homozygous deletions and 8 (2%) multiple duplications. We were unable to find any association between either stage or grade and urinary neoplasms with homozygous deletions. However, although there were only a limited number of patients with multiple duplications, 7/8 of them had highly malignant tumours (G2b-G4 or > or = T1; p = 0.02). CONCLUSIONS: Urinary bladder cancers constitute a spectrum of neoplasms with varying clinical manifestations. We were unable to establish a prognostic relevance for patients with tumours harbouring homozygous deletions at the CDKN2A/ARF locus. However, our data did indicate that patients with multiple duplications at the CDKN2A/ARF locus had poor survival. This suggests that multiple duplications, in combination with other genetic changes, have cooperative effects which have a negative outcome on urinary bladder cancer prognosis.
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2.
  • Sakano, S., et al. (författare)
  • A single-nucleotide polymorphism in the XPG gene, and tumour stage, grade, and clinical course in patients with nonmuscle-invasive neoplasms of the urinary bladder
  • 2006
  • Ingår i: BJU Int. - 1464-4096 .- 1464-410X. ; 97:4, s. 847-51
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate whether the single nucleotide polymorphism (SNP), Asp1104His (G3507C), in the XPG gene affects malignant phenotypes of nonmuscle-invasive urinary bladder neoplasms (NIBN), by investigating associations between the SNP and clinicopathological variables in patients with NIBN. PATIENTS AND METHODS: The 233 patients constituted newly diagnosed cases of primary NIBN in the Stockholm area. The Asp1104His polymorphism in the XPG gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The GC + CC genotypes were more frequent in stage pT1 tumours at initial diagnosis than pTa (odds ratio 1.9, 95% confidence interval 1.0-3.5, P = 0.048). The difference was larger in the young group (4.6, 1.9-11.8, P = 0.001). In the young group, the GC + CC genotypes were significantly more frequent in high-grade than in low-grade tumours (3.1, 1.5-6.8, P = 0.004) whereas in the older group the genotypes were less frequent in high-grade tumours (0.3, 0.1-0.7, P = 0.007). The XPG genotypes were not associated with tumour recurrence, stage progression or survival. CONCLUSION: These results suggest that the SNP in the XPG gene might be related to tumour invasiveness in NIBN.
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4.
  • Sanyal, S., et al. (författare)
  • Polymorphisms in XPD, XPC and the risk of death in patients with urinary bladder neoplasms
  • 2007
  • Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:1, s. 31-41
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a follow-up study on 311 patients with urinary bladder neoplasms to investigate the association of polymorphisms in DNA repair and cell growth regulatory genes with the clinical outcomes of this disease. We found that patients carrying the variant allele of XPD (K751Q) polymorphism were at lower risk of death (p = 0.04) than the noncarriers. Patients that were simultaneous carriers of variant alleles from XPD (K751Q) and XPC (K939Q) polymorphisms, showed lower risk of death than the other patients (p = 0.001). The variant allele carriers of MSH6 (G39E) polymorphism showed a higher risk for highly malignant disease (TaG3 +T1) than the non-carriers (p = 0.03). The variant allele carriers of XRCC1 (R399Q) polymorphism showed lower risk for recurrence (TaG2; p = 0.05) and death (T2+; p = 0.03) after instillation and radiotherapy than the non-carriers. After radiotherapy, an inverse association of the variant allele of OGG1 (S326C) polymorphism was observed with the risk of death (T2 +; p = 0.04). A significant low-risk for stage progression (p = 0.03) was observed in patients carrying the variant allele of H-ras (H27H) polymorphism. Our results are consistent with the notion that the XPD (K751Q) polymorphism either individually or in combination with the XPC (K939Q) polymorphism modulates the risk of death in patients with urinary bladder neoplasms.
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  • Resultat 1-4 av 4

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