School of Medicine, National Yang-Ming University School of Medicine, No. 155 Sec. 2 Linong Street, Taipei, Taiwan.
Cancer Sci. 2009 Feb;100(2):278-83. doi: 10.1111/j.1349-7006.2008.01031.x.
We analyzed the influence of codon 118 C→T polymorphism of ERCC1 on its protein expression levels, clinicopathological features, and outcome of 168 Chinese patients with metastatic colorectal carcinoma that had been treated with first-line FOLFOX-4 chemotherapy. A high prevalence of C/C genotype was noted (47.6%, n = 80; 168 patients in total). A marked increase of ERCC1 protein expression levels was also noted in patients with C/T or T/T genotypes (70%vs 20%; P < 0.01), which was associated with significantly lower response to FOLFOX-4 (36.4%vs 57.5%; p = 0.01), and shorter progression-free (7 months vs 13 months; P < 0.01) and overall (16 months vs 25 months; P < 0.01) survival times. By multivariate analysis, this polymorphism was also identified as an independent prognostic factor (P = 0.02). These data suggest that Asian populations have a significantly higher prevalence of the C/C genotype in ERCC1 codon 118, which could be a key determinant for good responses to oxaliplatin-based treatment and favorable outcomes.
我们分析了 ERCC1 密码子 118 C→T 多态性对其蛋白表达水平、临床病理特征和 168 例接受一线 FOLFOX-4 化疗的转移性结直肠癌患者预后的影响。我们注意到 C/C 基因型的高发生率(47.6%,n=80;总计 168 例患者)。还注意到 C/T 或 T/T 基因型患者 ERCC1 蛋白表达水平明显增加(70%比 20%;P<0.01),这与对 FOLFOX-4 的反应明显降低(36.4%比 57.5%;p=0.01)和无进展(7 个月比 13 个月;P<0.01)和总生存期(16 个月比 25 个月;P<0.01)较短有关。通过多变量分析,该多态性也被确定为独立的预后因素(P=0.02)。这些数据表明,亚洲人群 ERCC1 密码子 118 的 C/C 基因型发生率明显较高,这可能是对奥沙利铂为基础的治疗反应良好和结局有利的关键决定因素。