Genetic polymorphisms and treatment response in advanced non-small cell lung cancer
Genetic polymorphisms and treatment response in advanced non-small cell lung cancer
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DOI：
10.1016/j.lungcan.2006.12.002
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发表时间：
2007-05-01
期刊：
影响因子：
5.3
通讯作者：
Yu, Herbert
中科院分区：
文献类型：
--
作者：
Su, Dan;Ma, Shenglin;Yu, Herbert
背景：DNA修复和细胞凋亡的基因多态性被怀疑影响患者对癌症治疗的反应。为了评估遗传变异对化疗和/或放疗的影响，我们对ATM（A60 G）、ERCC 1和ERCC 2基因的4个单核苷酸多态性（SNP）进行了基因分型。（Asn118Asn），APE 1（Asn 148 Glu）和iASPP（A67 T），并检查它们与晚期非小细胞肺癌（NSCLC）患者的治疗反应的相关性。研究纳入了230例诊断为不可手术的晚期NSCLC患者。在这些患者中，76例接受了铂类化疗，125例接受了化疗加放疗，29例仅接受放疗。结果：在单纯化疗患者中，ERCC 1（Asn 118 Asn）基因型与化疗疗效显著相关。在Asn 118 Asn位点上携带1个或2个T等位基因（T/T+C/T）的患者对铂类药物化疗无效的可能性高于不携带T等位基因的患者（OR=4.10，95%CI：1.31-12.85）。对于同时接受化疗和放疗的患者，不同iASPP基因型（A67 T）患者的治疗反应似乎存在显著差异。携带A等位基因（A/T + A/A）的患者与不携带A等位基因的患者相比，更容易对联合化疗和放疗产生反应（OR = 0.25，95%CI：0.08-0.74）。APE 1基因多态性与治疗反应相关，而ATM基因多态性与治疗反应无关。结论：ERCC 1和iASPP基因多态性与NSCLC患者化疗或放化疗联合治疗反应相关。这些发现支持了与DNA修复或凋亡相关的遗传变异可能影响化疗或放疗对NSCLC的影响的观点。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Background: Genetic polymorphisms involved in DNA repair and apoptosis are suspected to influence patient response to cancer treatment. To evaluate the effect of genetic variations on chemotherapy and/or radiotherapy, we genotyped four single nucleotide polymorphisms (SNPs) in ATM (A60G), ERCC1 (Asn118Asn), APE1 (Asn148Glu), and iASPP (A67T), and examined their associations with treatment response among patients with advanced non-small cell lung cancer (NSCLC).Methods: Included in the study were 230 patients diagnosed with inoperable advanced NSCLC. Of these patients, 76 received platinum-based chemotherapy, 125 received chemotherapy plus radiation, and 29 received radiotherapy only. The SNPs were genotyped using the TaqMan methods.Results: Among the patients who received chemotherapy only, ERCC1 (Asn118Asn) genotype was significantly associated with treatment response. Patients with either one or two T alleles (T/T+C/T) at Asn118Asn were more likely not to respond to platinum-based chemotherapy compared to those without the T allele (OR=4.10, 95% Cl: 1.31-12.85). For patients who were treated with both chemotherapy and radiotherapy, treatment response seemed to differ substantially between patients with different genotypes of iASPP (A67T). Patients carrying an A allele (A/T + A/A) at A67T were more likely to respond to combined chemotherapy and radiotherapy compared to those not carrying the A allele (OR = 0.25, 95% CI: 0.08-0.74). An association with treatment response was also suggested for the selected polymorphism in APE1, but no association was found for the ATM polymorphism.Conclusion: We found that SNPs in ERCC1 and iASPP were associated with response to chemotherapy or combined chemotherapy and radiotherapy in NSCLC patients. These findings support the notion that genetic variations related to DNA repair or apoptosis may affect the effect of chemotherapy or radiation on NSCLC. (c) 2006 Elsevier Ireland Ltd. All rights reserved.