Department of Medical Oncology, Meram Medical Faculty, Selcuk University, Meram, 42080 Konya, Turkey.
J Cancer Res Clin Oncol. 2010 Jun;136(6):803-9. doi: 10.1007/s00432-009-0720-3. Epub 2009 Nov 12.
Previous studies have suggested that DNA repair enzyme polymorphisms may bear prognostic value in metastatic colorectal carcinoma (MCRC).
We prospectively treated 43 MCRC patients with irinotecan-based regimens (XELIRI or IFL). Allelic variants of the XRCC1 gene at codon 399 and XPD gene at codon 751 were analyzed in lymphocyte DNA by PCR-RFLP. Clinical outcome variables: overall survival (OAS), progression-free survival (PFS) and the occurrence of grade 3 or 4 hematological and gastrointestinal (GIS) toxicities were evaluated.
In the univariate analysis for OAS (n = 43) only XPD and XRCC1 polymorphisms were significant (P = 0.05 and P = 0.04, respectively). After adjustment for performance status (ECOG = 0, 1 vs. 2) and disease extent (single vs. multiple metastatic site), XRCC1 genotype and performance status retained significance (HR = 2.85, P = 0.04, and HR = 3.19, P = 0.02, respectively). Gln/Gln genotype was associated with the greatest risk of death. Type of presentation (metastatic vs. local disease at first presentation) was the only significant predictor of PFS in the univariate analysis (n = 40, P = 0.003). After adjustment for performance status and disease extent, type of presentation retained its significance (HR = 4.35, P = 0.003). None of the toxicities was associated with these genotypes.
XRCC1 genotype independently predicted overall survival in metastatic colorectal carcinoma patients treated with irinotecan-based chemotherapy.
先前的研究表明，DNA 修复酶多态性可能与转移性结直肠癌（MCRC）的预后有关。
我们前瞻性地用伊立替康为基础的方案（XELIRI 或 IFL）治疗 43 例 MCRC 患者。采用 PCR-RFLP 法分析淋巴细胞 DNA 中 XRCC1 基因密码子 399 位和 XPD 基因密码子 751 位的等位基因变异。临床结局变量：总生存期（OAS）、无进展生存期（PFS）和 3 或 4 级血液学和胃肠道（GIS）毒性的发生。
在 OAS 的单因素分析（n=43）中，仅 XPD 和 XRCC1 多态性有显著意义（P=0.05 和 P=0.04）。在调整了体能状态（ECOG=0、1 与 2）和疾病范围（单发或多发转移部位）后，XRCC1 基因型和体能状态仍有意义（HR=2.85，P=0.04，HR=3.19，P=0.02）。Gln/Gln 基因型与死亡风险增加相关。在单因素分析中（n=40），首发时的表现类型（转移性与局部疾病）是 PFS 的唯一显著预测因素（P=0.003）。在调整了体能状态和疾病范围后，表现类型仍有意义（HR=4.35，P=0.003）。这些基因型与任何毒性无关。
在接受伊立替康为基础化疗的转移性结直肠癌患者中，XRCC1 基因型独立预测总生存期。
