A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen.
A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen.
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DOI：
10.1038/tpj.2012.31
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Toffoli G
中科院分区：
文献类型：
--
作者：
Cecchin E;D'Andrea M;Lonardi S;Zanusso C;Pella N;Errante D;De Mattia E;Polesel J;Innocenti F;Toffoli G
结直肠癌（CRC）中药物基因组标记物的发现可能具有特异性。FOLFOX4被用于CRC的辅助和转移情况。本前瞻性研究旨在验证在辅助环境下转移性肿瘤毒性的药物基因组学标记（即GSTP1-rs947894和-rs1138272； GSTM1-null基因型；AGXT-rs4426527， -rs34116584和del-74 bp），并发现其他标记。接受FOLFOX4辅助治疗的CRC患者（n = 144）对29个基因的57个多态性进行了基因分型。≥2级神经毒性与ABCC1 （rs2074087：比值比= 0.43(0.22-0.86)）和ABCC2 (rs3740066: 2.99（1.16-7.70）的单核苷酸多态性相关（校正后q值<0.1）；rs1885301: 3.06 (1.35 - -6.92);rs4148396: 4.69 (1.60 - -13.74);rs717620: 14.39(1.63 - -127.02))。hMSH6-rs3136228与3-4级中性粒细胞减少症相关（3.23(1.38 ~ 7.57)，q值= 0.0937）。XRCC3-rs1799794与3-4级非血液学毒性相关（8.90(2.48-31.97)，q值= 0.0150）。先前在转移性结直肠癌中发现的标志物没有得到验证。我们在运输和DNA修复基因中发现了新的毒性标记。如果在其他研究中得到证实，它们可以帮助识别有毒性风险的患者。
The discovery of pharmacogenomic markers in colorectal cancer (CRC) could be setting-specific. FOLFOX4 is employed in the adjuvant and metastatic setting in CRC. This prospective study is aimed to validate in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting (that is, GSTP1-rs947894, and -rs1138272; GSTM1-null genotype; AGXT-rs4426527, -rs34116584 and del-74 bp), and to discover additional markers. CRC patients (n = 144) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes. Grade ≥2 neurotoxicity was associated false discovery rate-adjusted q-value <0.1) with single-nucleotide polymorphisms in ABCC1 (rs2074087: odds ratio = 0.43(0.22–0.86)), and ABCC2 (rs3740066: 2.99(1.16–7.70); rs1885301: 3.06(1.35–6.92); rs4148396: 4.69(1.60–13.74); rs717620: 14.39(1.63–127.02)). hMSH6-rs3136228 was associated with grade 3–4 neutropenia (3.23(1.38–7.57), q-value = 0.0937). XRCC3-rs1799794 was associated with grade 3–4 non-hematological toxicity (8.90(2.48–31.97), q-value = 0.0150). The markers previously identified in metastatic CRC were not validated. We have identified new markers of toxicity in genes of transport and DNA repair. If validated in other studies, they could help to identify patients at risk of toxicity.
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影响因子：
37.3
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
通讯作者：
Fiehn O
影响因子：
5
作者：
Adelsberger, H;Quasthoff, S;Lersch, C
通讯作者：
Lersch, C
影响因子：
5.7
作者：
Chen, Yen-Chung;Tzeng, Cheng-Hwai;Wang, Wei-Shu
通讯作者：
Wang, Wei-Shu
影响因子：
11.5
作者：
Gamelin, Laurence;Capitain, Olivier;Gamelin, Erick
通讯作者：
Gamelin, Erick
影响因子：
11.5
作者：
Martin, Lainie P.;Hamilton, Thomas C.;Schilder, Russell J.
通讯作者：
Schilder, Russell J.