Sanyal Somali, De Verdier Petra J, Steineck Gunnar, Larsson Per, Onelöv Erik, Hemminki Kari, Kumar Rajiv
Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
Acta Oncol. 2007;46(1):31-41. doi: 10.1080/02841860600812693.
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.
我们对311例膀胱肿瘤患者进行了一项随访研究,以调查DNA修复和细胞生长调节基因多态性与该疾病临床结局之间的关联。我们发现,携带XPD(K751Q)多态性变异等位基因的患者死亡风险低于非携带者(p = 0.04)。同时携带XPD(K751Q)和XPC(K939Q)多态性变异等位基因的患者,其死亡风险低于其他患者(p = 0.001)。MSH6(G39E)多态性变异等位基因携带者比非携带者患高恶性疾病(TaG3 +T1)的风险更高(p = 0.03)。XRCC1(R399Q)多态性变异等位基因携带者在灌注和放疗后复发(TaG2;p = 0.05)和死亡(T2+;p = 0.03)的风险低于非携带者。放疗后,观察到OGG1(S326C)多态性变异等位基因与死亡风险(T2 +;p = 0.04)呈负相关。携带H-ras(H27H)多态性变异等位基因的患者出现分期进展的风险显著较低(p = 0.03)。我们的结果与以下观点一致,即XPD(K751Q)多态性单独或与XPC(K939Q)多态性联合可调节膀胱肿瘤患者的死亡风险。