2010American Journal of Clinical OncologyRequires access

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

Fan Li, Xinchen Sun, Ning Sun, Shukui Qin, Hongyan Cheng, Jifeng Feng, Baoan Chen, Lü Cheng, Zuhong Lu, Jiazhong Ji, Zhou Yingfeng

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Abstract

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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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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Available abstract

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.

Key concepts: ERCC1, Nucleotide excision repair, Medicine, Carboplatin, Single-nucleotide polymorphism, Oncology, Cisplatin, Lung cancer

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