Polymorphisms in XPD, XPC and the risk of death in patients with urinary bladder neoplasms.
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.
Sanyal
Somali
S
Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
De Verdier
Petra J
PJ
Steineck
Gunnar
G
Larsson
Per
P
Onelöv
Erik
E
Hemminki
Kari
K
Kumar
Rajiv
R
D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human