DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy
DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy
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DOI：
10.1200/jco.2006.05.8768
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发表时间：
2006-09-10
影响因子：
45.3
通讯作者：
Sanchez-Cespedes, Montserrat
中科院分区：
文献类型：
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作者：
Quintela-Fandino, Miguel;Hitt, Ricardo;Sanchez-Cespedes, Montserrat
目的顺铂通过DNA交联杀死肿瘤细胞。 DNA 修复基因功能的改变可能会影响 DNA 修复能力并影响癌症患者对顺铂的反应。我们研究了DNA修复基因的单核苷酸多态性（SNP）是否可以预测头颈鳞状细胞癌（SCCHN）患者对顺铂的反应或预后。方法采用聚合酶链反应-限制性片段长度多态性（RFLP）方法来确定SNP的频率：XPD-Asp312Asn， 103 名 IV 期 SCCHN 患者外周淋巴细胞 DNA 中的 XPD-Lys751Gln、ERCC1-C8092A 和 XRCC1-Arg399Gln。 结果 不同基因型的频率分别为纯合共同等位基因、杂合和纯合多态性变异：53%、 ERCC1 为 40%，7%； XPD-312 为 50%、42% 和 8%； XPD751 为 35%、57% 和 8%； XRCC1 为 35%、51% 和 13%。与至少具有一种多态性变异的患者相比，在所有测试的 SNP 上仅具有共同等位基因的患者的中位总生存期为 5.1 个月（范围为 4.3 至 6.0 个月）（P
PurposeCisplatin kills tumor cells through DNA cross linking. Alterations in the function of DNA repair genes may affect DNA repair proficiency and influence cancer patients' response to cisplatin. We studied whether single nucleotide polymorphisms (SNPs) of DNA repair genes predict the response to cisplatin or prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN).MethodsA polymerase chain reaction-restriction fragment length polymorphism (RFLP) approach was used to determine the frequency of the SNPs: XPD-Asp312Asn, XPD-Lys751Gln, ERCC1-C8092A, and XRCC1-Arg399Gln in DNA from peripheral lymphocytes of 103 stage IV SCCHN patients.ResultsThe frequencies of the distinct genotypes were, respectively, for the homozygous common allele, heterozygous and homozygous polymorphic variant: 53%, 40%, and 7% for ERCC1; 50%, 42%, and 8% for XPD-312; 35%, 57%, and 8% for XPD751; and 35%, 51%, and 13% for XRCC1. Patients with only common alleles at all the SNPs tested had a median overall survival of 5.1 months (range, 4.3 to 6.0 months) as compared with not reached for patients with at least one polymorphic variant (P