Association between DNA-repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy
Association between DNA-repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy
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DOI：
10.2217/pgs.11.109
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发表时间：
2011-12-01
期刊：
影响因子：
2.1
通讯作者：
Cantore, Maurizio
中科院分区：
文献类型：
--
作者：
Giovannetti, Elisa;Pacetti, Paola;Cantore, Maurizio
目的：这项多中心研究评估了 8 个基因的 11 个候选多态性与接受等效联合化疗方案治疗的胰腺癌患者结局的关联：顺铂/表阿霉素/卡培他滨/吉西他滨、顺铂/多西他赛/卡培他滨/吉西他滨和吉西他滨/卡培他滨加表阿霉素/顺铂动脉内输注。患者和方法：为此，我们对 122 名 III/IV 期胰腺癌患者的 DNA 多态性进行了评估，并使用 Pearson-chi(2) 和时序检验评估了它们与毒性/反应以及无进展生存期 (PFS) 和总生存期的关联。结果：携带 XPD Gln751Gln、XPD Asp312Asn + Asn312Asn 或 XRCC1 Arg399Gln + Gln399Gln 基因型的患者预后较差。 XPD Gln751Gln（风险比：1.9；p = 0.003）以及两种以上风险基因型的组合（风险比：2.7；p < 0.001）在多变量分析中成为死亡风险的独立预测因子。没有观察到与毒性的相关性。相反，XPD Gln751Gln 与较短的 PFS 相关，而与吉西他滨单药治疗患者的总生存率/PFS 缺乏相关性，表明其仅在铂类治疗方案中发挥作用。结论：DNA 修复基因的多态性似乎是对基于吉西他滨/顺铂的联合化疗方案主要耐药的候选生物标志物。相对较小的样本量，加上本研究的回顾性和探索性设计，意味着这些结果应被视为假设生成器，并应在更大且设计充分的回顾性/前瞻性研究中进一步评估。
Aim: This multicenter study evaluated the association of 11 candidate polymorphisms in eight genes with outcome of pancreatic cancer patients treated with the equivalent polychemotherapeutic regimens: cisplatin/epirubicin/capecitabine/gemcitabine, cisplatin/docetaxel/capecitabine/gemcitabine and gemcitabine/capecitabine plus epirubicin/cisplatin intra-arterial infusion. Patients & methods: Towards this end, polymorphisms were assessed in DNA from 122 pancreatic cancer stage-III/IV patients, and their associations with toxicity/response and progression-free survival (PFS) and overall survival were evaluated using Pearson-chi(2) and log-rank test. Results: Patients harboring XPD Gln751Gln, XPD Asp312Asn + Asn312Asn or XRCC1 Arg399Gln + Gln399Gln genotypes had a worse prognosis. XPD Gln751Gln (hazard ratio: 1.9; p = 0.003), as well as a combination of over two risk genotypes (hazard ratio: 2.7; p < 0.001), emerged as independent predictors for death risk at multivariate ana-lysis. No correlations were observed with toxicity. Conversely, XPD Gln751Gln was associated with shorter PFS, while the lack of association with overall survival/PFS in gemcitabine monotherapy-treated patients suggested its role only for platinum-based regimens. Conclusion: Polymorphisms of DNA-repair genes appear to be candidate biomarkers of primary resistance to gemcitabine/cisplatin-based polychemotherapeutic regimens. The relatively small sample size, coupled with the retrospective and exploratory design of the present study, imply that these results should be considered as hypothesis generators, and should be further evaluated in larger and adequately designed retrospective/prospective studies.