4.2 Article

Association Between Polymorphisms of ERCC1 and XPD and Clinical Response to Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/COC.0b013e3181b9cedc

关键词

single nucleotide polymorphism; gene-chip; ERCC1; XPD; nucleotide excision repair; NSCLC; chemotherapy

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资金

  1. Prophase Force-Study program of JiangSu Province Nature Fund [BK2005203]
  2. Medicine Science Technology Research Eleventh Five-Year Program of PLA [06MA111]
  3. Focal Project of Nanjing Medicine Technology Development [ZKX05030]

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Background and Objective: DNA repair capacity is correlated with sensitivity of cancer cells toward platinum-based chemotherapy. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in polymorphisms of DNA repair gene ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) were associated with the tumor response in advanced non-small- cell lung cancer (NSCLC) patients received platinum-based chemotherapy in Chinese population. Methods: Totally 115 patients with advanced NSCLC were routinely treated with cisplatin-or carboplatin-based chemotherapy, and clinical response was evaluated after 2 cycles. Three dimensions (3-D) polyacrylamide gel-based DNA microarray method was used to evaluate the genotypes of ERCC1 Asn118Asn (354 CT), Gln504Lys (8092 CA) and XPD Lys751Gln (35931 AC). Results: The C -> T change of ERCC1 Asn118Asn polymorphism and the C -> A change of ERCC1 Gln504Lys polymorphism have statistically significant association with elevated or descendent platinum-based chemotherapy response respectively. Conclusion: The polymorphic status of ERCC1 might be the promising ancillary marker for predicting treatment response of advanced stage NSCLC patients. The DNA microarray-based method is accurate, high-throughput and inexpensive, suitable for SNP genotyping in a large number of individuals.

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