Gan Yi, Li Xiao-Rong, Chen Dao-Jin, Wu Jun-Hui
Department of General Surgery, 3rd Xiang-Ya Hospital of Central South University, Changsha, China.
Asian Pac J Cancer Prev. 2012;13(11):5721-4. doi: 10.7314/apjcp.2012.13.11.5721.
We conducted this study to detect associations between XRCC1 Arg399Gln and XPD Lys751Gln genotypes and survival of colorectal cancer patients treated with 5-FU/oxalipatin chemotherapy. We included 289 Chinese patients with advanced colorectal cancer, who had received 5-FU/oxalipatin chemotherapy as first-line treatment from January 2005 to January 2007. All patients were followed up till Nov. 2011. Genotyping for XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with the PCR-RFLP method. In our study, we found the XRCC1 399 Gln/Gln genotype to confer significantly higher rates of response to chemotherapy when compared to the Arg/Arg genotype [OR (95% CI)=2.56(1.57-2.55)]. patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR (95% CI)=1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survival time and significantly lower risk of death than did those with the Arg/Arg genotype [HR (95% CI)=0.66(0.36-0.95)]. Similarly, those carrying the XPD 751Gln/Gln genotype had 0.51-fold the risk of death of those with XPD 751Lys/Lys [HR (95% CI)=0.51(0.33-0.94)]. In conclusion, it is suggested that the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms should be routinely assessed to determine colorectal patients who are more likely to benefit from 5-FU/oxalipatin chemotherapy.
我们开展这项研究,旨在检测XRCC1基因第399位密码子精氨酸突变为谷氨酰胺(Arg399Gln)以及XPD基因第751位密码子赖氨酸突变为谷氨酰胺(Lys751Gln)的基因型与接受5-氟尿嘧啶/奥沙利铂化疗的结直肠癌患者生存率之间的关联。我们纳入了289例中国晚期结直肠癌患者,这些患者在2005年1月至2007年1月期间接受了5-氟尿嘧啶/奥沙利铂一线化疗。所有患者均随访至2011年11月。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对XRCC1基因Arg399Gln和XPD基因Lys751Gln多态性进行基因分型。在我们的研究中,我们发现与Arg/Arg基因型相比,XRCC1基因399 Gln/Gln基因型的患者对化疗的反应率显著更高[比值比(95%可信区间)=2.56(1.57 - 2.55)]。XPD基因751 Gln/Gln基因型的患者对化疗的反应率显著更高[比值比(95%可信区间)=1.54(0.87 - 2.65)],并且与Arg/Arg基因型的患者相比,XRCC1基因399 Gln/Gln基因型的患者平均生存时间更长,死亡风险显著更低[风险比(95%可信区间)=0.66(0.36 - 0.95)]。同样,携带XPD基因751Gln/Gln基因型的患者死亡风险是携带XPD基因751Lys/Lys基因型患者的0.51倍[风险比(95%可信区间)=0.51(0.33 - 0.94)]。总之,建议常规评估XRCC1基因Arg399Gln和XPD基因Lys751Gln多态性,以确定更可能从5-氟尿嘧啶/奥沙利铂化疗中获益的结直肠癌患者。