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

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

doi:10.1097/coc.0b013e3181b9cedc

Cited by 51 publications

(42 citation statements)

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“…Previous studies have demonstrated the correlation between gene polymorphisms involved in DNA repair and chemotherapy response (33,34). By means of testing peripheral blood, our team has already done some work in assessing the role of DNA repair gene polymorphisms including XPA and XPD in the response of platinum-based regimen in advanced NSCLC patients (12,20,21,35).…”

Section: Discussionmentioning

confidence: 99%

“…The genotyping procedure involved polymerase chain reaction (PCR) and the three-dimensional (3-D) polyacrylamide gel-based DNA microarray method (23). Probes and primers were designed by Primer Premier 5.0 software as previously described (20,21). One of each pair primers was modified with acrylamide phosphoramidite (Acrydite TM ; Matrix Technologies, Hudson, USA) at 5′-terminal.…”

Section: Dna Collection and Genotypingmentioning

confidence: 99%

“…The XPD lysine 751 glutamine polymorphism was reportedly associated with survival in NSCLC patients treated with platinum combined chemotherapy; however, studies thus far have yielded inconclusive evidence of an adverse effect of variant XPD751 genotype on survival (16)(17)(18)(19). We have previously reported that XPA A23G polymorphism was identified to significantly increase the response to platinum-based chemotherapy, while no significant association was found between XPD polymorphism and treatment response (20,21).…”

Section: Introductionmentioning

confidence: 98%

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Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Cheng

Qin

Sun

et al. 2013

Technol Cancer Res Treat

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Platinum-based chemotherapy is a primary treatment for patients with advanced non-small cell lung cancer (NSCLC). Considering individual differences, an effective and convenient method is urgently needed to identify the sensitivity of individual patient to platinum based regimen. Genetic variants in DNA repair genes are presumed to represent important determinants of drug efficacy. Our previous studies have demonstrated the involvement of xeroderma pigmentosum group A (XPA) codon23 and xeroderma pigmentosum group D (XPD) codon751 single-nucleotide polymorphisms (SNPs) in clinical response to platinum based chemotherapy in advanced NSCLC patients. Thus, a follow-up study was carried out to investigate the relevance of these genotypes and survival of the cohort (n 5 115). The threedimensional (3-D), polyacrylamide gel-based DNA microarray method was used to assess the genotypes of XPA and XPD in peripheral lymphocytes. Log-rank test revealed that the variant genotypes of XPA23 (A/G1G/G) were associated with significantly longer progression-free survival (PFS) (6.0 m vs. 10.6 m, log-rank P 5 0.001) and overall survival (OS) (11.2 m vs. 20.8 m, log-rank P 5 0.001). In Cox proportional hazards model, the hazard ratio (HR) for death in patients with G allele was 0.65 (P 5 0.049). While no significant differences were observed in PFS or OS according to XPD Lys751Gln genotypes (log-rank P  0.05).In combination with our previous short-term clinical results, this study further confirmed that by detecting the SNPs in blood cells, XPA A23G polymorphic variants might be a promising biomarker in predicting a favor prognosis of NSCLC patients and be helpful towards designing individualized treatments.

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Section: Discussionmentioning

confidence: 99%

Section: Dna Collection and Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Cheng

Qin

Sun

et al. 2013

Technol Cancer Res Treat

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“…Previous studies had reported that patients carrying the ERCC1 CC genotype or C allele at C118T had a higher response rate to platinum-based chemotherapy Kalikaki et al, 2009;Li et al, 2010). Isla et al (2004) and Ryu et al (2004) both found that advanced NSCLC patients with the ERCC1 118 CC genotype had better survival, but no relationships were found between the response and 118 CC genotype after platinum-based treatment.…”

Section: Discussionmentioning

confidence: 93%

“…Preclinical data suggests that the ERCC1 C8092A and C118T polymorphisms could affect the ERCC1 mRNA and protein levels, thus leading to different platinum sensitivity and increased DNA repair capacity (Chen et al, 2000;Yu et al, 2000;Park et al, 2002). ERCC1 polymorphisms have been reported to predict better response Kalikaki et al, 2009;Li et al, 2010) or survival in NSCLC patients treated with platinum-based chemotherapy Ryu et al, 2004;Zhou et al, 2004). However, published reports of the associations between ERCC1 SNPs and clinical efficacy from individual studies are controversial (de las Peñas et al, 2006;Tibaldi et al, 2008;Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Hong

Wang

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:Objective: The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T excision repair cross-complementation group 1 (ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods: A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 C118T were genotyped using the TaqMan methods. Results: The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype (TT or CT) (41.2% versus 19.1%, P=0.01). Median time to progression (TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype (7.6 months versus 5.0 months, P=0.003). No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions: Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

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Germline polymorphisms in patients with advanced nonsmall cell lung cancer receiving first‐line platinum‐gemcitabine chemotherapy

Joerger

Burgers

Baas

et al. 2011

Cancer

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BACKGROUND:The authors assessed the impact of germline polymorphisms on clinical outcome in patients with advanced nonsmall cell lung cancer (NSCLC) who received platinum-gemcitabine (PG) chemotherapy. METHODS: In total, 137 patients with stage IIIB/IV NSCLC were included who received first-line PG chemotherapy (74% of patients received cisplatin, and 26% received carboplatin). Twenty-three germline polymorphisms that were identified in peripheral blood samples were analyzed for progression-free survival (PFS), treatment response, overall survival (OS), and toxicity. RESULTS: The median PFS was 5.8 months, the median OS was 10.2 months, and 44 patients (32%) had a partial treatment response. Carriers of the excision repair cross-complementation group 1 (ERCC1) mutant thymine (T) allele had a lower treatment response rate (29% vs 52%; P ¼ .02), shorter PFS (adjusted hazard ratio [HR], 1.60; P ¼ .04), and shorter OS (adjusted HR, 1.54; P ¼ .05) compared with carriers of the wild-type cytosine/cytosine (CC) genotype. The xeroderma pigmentosum group A member 10 (XPD10) mutant adenine (A) allele (adjusted HR, 0.64; P ¼ .04) and the x-ray cross-complementing group 1 (XRCC1) mutant guanine (G) allele (adjusted HR, 0.51; P ¼ .02) also were independent predictors of OS. Carriers of the mutant adenosine triphosphate-dependent DNA helicase Q1 (RECQ1) C allele or the mutant cytidine deaminase (CDA) C allele were more likely to experience severe leukocytopenia (26% vs 10% [P ¼ .03] and 28% vs 11% [P ¼ .02], respectively) compared with wild-type genotype carriers. Patients who carried the homozygous mutant glutathione S-transferase p 1(GSTP1) GG genotype were at considerable risk for severe platinum-associated polyneuropathy (18% vs 3% in wild-type vs heterozygous mutant patients, respectively; P ¼ .01). CONCLUSIONS: To the authors' knowledge, this is the first prospective study to date in patients with advanced NSCLC describing predictive germline polymorphisms not only for the clinical activity of PG chemotherapy (ERCC1, XPD10) but also for its toxicity (GSTP1, RECQ1, CDA). Nonplatinum-containing chemotherapy in carriers of the ERCC1 T allele or the XPD10 G allele should be studied prospectively. Cancer 2012;118:2466-

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

Abstract: 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.

Cited by 51 publications

References 30 publications

Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Predictive Effect of XPA and XPD Polymorphisms on Survival of Advanced NSCLC Patients Treated with Platinum-Based Chemotherapy: A Three-Dimensional (3-D), Polyacrylamide Gel-Based DNA Microarray Method

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Germline polymorphisms in patients with advanced nonsmall cell lung cancer receiving first‐line platinum‐gemcitabine chemotherapy

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