Martinez-Balibrea Eva, Abad Albert, Aranda Enrique, Sastre Javier, Manzano Jose Luis, Díaz-Rubio Eduardo, Gómez-España Auxiliadora, Aparicio Jorge, García Teresa, Maestu Inmaculada, Martínez-Cardús Anna, Ginés Alba, Guino Elisabet
Medical Oncology Service, Hospital Universitari Germans Trias i Pujol-Institut Català d'Oncologia, Badalona, Barcelona, Spain.
Eur J Cancer. 2008 Jun;44(9):1229-37. doi: 10.1016/j.ejca.2008.03.025. Epub 2008 Apr 28.
We studied the role of TS (5'VNTR, 5'SNP and 3'UTR), XRCC1-399, XPD-751, ERCC1-118 and XRCC3-241 genetic polymorphisms in tailoring fluroropyrimidine/oxaliplatin treatment. For this purpose, 110 XELOX (capecitabine/oxaliplatin)- or FUOX (fluorouracil/oxaliplatin)-treated metastatic colorectal cancer patients were selected prospectively for genotyping. In the FUOX group, TS-3'UTR +6bp/+6bp (hazards ratio, HR=2.62, p=0.007) and ERCC1-118C/T or C/C (HR=1.96, p=0.050) genotypes correlated with a shorter progression-free survival (PFS). When analysed jointly, the higher the number of favourable genotypes (FG) the longer the PFS (6.8m, 9.6m and 25.8m for 0, 1 or 2 FG; p=0.005). Disease-control rate was 100% in patients with 2 FG (87% and 38.5% for 1 or 0 FG; p=0.001). In the multivariate analysis, ERCC1-118 (HR=2.12, p=0.0037) and TS-3'UTR (HR=2.68, p=0.006) were strong independent prognostic factors. According to this, patients harbouring TS-3'UTR +6bp/+6bp and ERCC1-118C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment.
我们研究了胸苷酸合成酶（TS，包括5'可变数目串联重复序列、5'单核苷酸多态性和3'非翻译区）、X线修复交叉互补蛋白1（XRCC1）-399、XPD-751、切除修复交叉互补蛋白1（ERCC1）-118和XRCC3-241基因多态性在氟尿嘧啶/奥沙利铂治疗方案调整中的作用。为此，前瞻性地选取了110例接受XELOX（卡培他滨/奥沙利铂）或FUOX（氟尿嘧啶/奥沙利铂）治疗的转移性结直肠癌患者进行基因分型。在FUOX组中，TS-3'非翻译区+6bp/+6bp（风险比，HR = 2.62，p = 0.007）以及ERCC1-118C/T或C/C（HR = 1.96，p = 0.050）基因型与无进展生存期（PFS）较短相关。联合分析时，有利基因型（FG）数量越多，PFS越长（0、1或2个FG时分别为6.8个月、9.6个月和25.8个月；p = 0.005）。2个FG患者的疾病控制率为100%（1个或0个FG时分别为87%和38.5%；p = 0.001）。多因素分析中，ERCC1-118（HR = 2.12，p = 0.0037）和TS-3'非翻译区（HR = 2.68，p = 0.006）是强有力的独立预后因素。据此，在基于奥沙利铂的一线治疗中，携带TS-3'非翻译区+6bp/+6bp以及ERCC1-118C/T或C/C基因型的患者可能更适合接受卡培他滨而非5-氟尿嘧啶治疗。
