Kim Hee Seung, Kim Mi-Kyung, Chung Hyun Hoon, Kim Jae Weon, Park Noh Hyun, Song Yong Sang, Kang Soon Beom
Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Jongno-Gu, Seoul, Republic of Korea.
Gynecol Oncol. 2009 May;113(2):264-9. doi: 10.1016/j.ygyno.2009.01.002. Epub 2009 Feb 8.
We sought to evaluate the affect of genetic polymorphisms on clinical outcomes in patients with epithelial ovarian cancer (EOC).
Clinical data of 118 patients between March 2001 and November 2006 were reviewed. They underwent staging laparotomy followed by adjuvant chemotherapy using taxanes and platinum compounds. We investigated ERCC1 N118N, ERCC1 8092C>A, ERCC2 K751Q, XRCC1 R399Q, XRCC1 R194W, ABCB1 3435C>T, ABCB1 2677G>T/A, GSTP1 I105V, GSTM1 and GSTT1 polymorphisms with single base primer assay.
The multivariate logistic regression analysis revealed that non-null genotype in GSTT1 polymorphism was a poor prognostic factors for overall response (adjusted OR, 0.29; 95% CI, 0.17-0.67), and A/A genotype in GSTP1 I105V polymorphism and T/T or T/A or A/A genotype in ABCB1 2677G>T/A polymorphism were significant risk factors for grade 3 or 4 hematological (adjusted OR, 3.08; 95% CI, 1.12-8.43) and gastrointestinal toxicities (adjusted OR, 9.74; 95% CI, 1.59-15.85), respectively. Moreover, The multivariate Cox's proportional hazard regression analysis showed that C/A or A/A genotype in ERCC1 8092C>A polymorphism and non-null genotype in GSTT1 polymorphism were prognostic factors for poor progression-free survival (adjusted HR, 1.94; 95% CI, 1.07-3.51) and poor overall survival (adjusted HR, 1.65; 95% CI, 1.79-3.42), respectively.
Genetic polymorphisms such as ERCC1 8092C>A, ABCB1 2677G>T/A, GSTP1 I105V and GSTT1 polymorphisms may affect drug response, toxicity and survival in patient with EOC who received taxane- and platinum-based chemotherapy after surgery. However, large-scale, prospective clinical studies are required for evaluating the role of genetic polymorphisms.
我们试图评估基因多态性对上皮性卵巢癌（EOC）患者临床结局的影响。
回顾了2001年3月至2006年11月期间118例患者的临床资料。他们接受了分期剖腹手术，随后使用紫杉烷和铂类化合物进行辅助化疗。我们采用单碱基引物分析法研究了ERCC1 N118N、ERCC1 8092C>A、ERCC2 K751Q、XRCC1 R399Q、XRCC1 R194W、ABCB1 3435C>T、ABCB1 2677G>T/A、GSTP1 I105V、GSTM1和GSTT1基因多态性。
多因素逻辑回归分析显示，GSTT1基因多态性中的非无效基因型是总体反应的不良预后因素（校正OR，0.29；95%CI，0.17 - 0.67），GSTP1 I105V基因多态性中的A/A基因型以及ABCB1 2677G>T/A基因多态性中的T/T或T/A或A/A基因型分别是3级或4级血液学毒性（校正OR，3.08；95%CI，1.12 - 8.43）和胃肠道毒性（校正OR，9.74；95%CI，1.59 - 15.85）的显著危险因素。此外，多因素Cox比例风险回归分析表明，ERCC1 8092C>A基因多态性中的C/A或A/A基因型以及GSTT1基因多态性中的非无效基因型分别是无进展生存期差（校正HR，1.94；95%CI，1.07 - 3.51）和总生存期差（校正HR，1.65；95%CI，1.79 - 3.42）的预后因素。
ERCC1 8092C>A、ABCB1 2677G>T/A、GSTP1 I105V和GSTT1等基因多态性可能影响接受手术后紫杉烷和铂类化疗的EOC患者的药物反应、毒性和生存期。然而，需要大规模的前瞻性临床研究来评估基因多态性的作用。
