No association between<i>XRCC1</i>polymorphisms and survival in non-small-cell lung cancer patients treated with platinum-based chemotherapy

Yuan, Peng; Liu, Li; Wu, Chen; Zhong, Rong; Yu, Dianke; Wu, Jing; Xu, Yi-Hua; Nie, Shaoping; Miao, Xiaoping; Sun, Yan; Xu, Binghe; Lin, Dongxin

doi:10.4161/cbt.10.9.13238

Cited by 13 publications

(17 citation statements)

References 33 publications

(53 reference statements)

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“…11 Two Asian studies did not identify any association between XRCC1 polymorphisms and clinical outcome in patients with advanced NSCLC who received platinum-based chemotherapy. 13,14 Overall, the data are consistent on the association of the XRCC1 G allele with a worse clinical outcome in patients with advanced NSCLC who receive platinumbased chemotherapy. Therefore, patients carrying the XRCC1 mutant G allele may be good candidates for receiving nonplatinum-containing chemotherapy.…”

Section: Discussionsupporting

confidence: 69%

“…11 There are conflicting data on the effect of the G allele in codon 399 of x-ray crosscomplementing group 1 (XRCC1) on clinical outcome in patients with advanced NSCLC. [11][12][13][14] The thymine (T) allele in codon 241 of XRCC3 was identified as a favorable marker of survival in 1 clinical study. 7 For gemcitabine, different drug pathway-associated gene polymorphisms have been described, 15,16 but their clinical relevance remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

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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“…Three of these studies were conducted on Caucasian patients, and 10 were conducted on Chinese patients. Six were published in English-language journals (23,(26)(27)(28)(29)35). Seven were published in Chinese-language journals (9, 10, 34, 36-39).…”

Section: Resultsmentioning

confidence: 99%

“…Gao ( an article (23,(28)(29)(30). Survival probabilities were transcribed using Grafula 3, version 2.10.…”

Section: Discussionmentioning

confidence: 99%

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Predictive Value of XRCC1 Gene Polymorphisms on Platinum-Based Chemotherapy in Advanced Non–Small Cell Lung Cancer Patients: A Systematic Review and Meta-analysis

Liu

Zhou

et al. 2012

Clinical Cancer Research

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Purpose: Published data have shown conflicting results about the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms (Arg399Gln and Arg194Trp) and clinical outcome of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis is needed to provide a systematic review of the published findings.Experimental Design: We conducted a systematic review and meta-analysis to evaluate the predictive value of XRCC1 gene polymorphisms on clinical outcome up to October 1, 2010. The quality of each study was scored on the basis of predefined criteria.Results: A total of 13 eligible follow-up studies met all the inclusion criteria. The XRCC1194Trp allele was found to be significantly associated with a favorable response rate relative to 194Arg [Trp vs. Arg: OR, 1.88; 95% confidence interval (CI), 1.48-2.38]. XRCC1399Gln was less favorably associated with both response rate (Gln vs. Arg: OR, 0.67; 95% CI, 0.52-0.87) and overall survival (Gln vs. Arg: HR, 1.30; 95% CI, 1.04-1.63) than 399Arg in analyses using all available studies; but these associations became insignificant when only high-quality studies were used.Conclusion: These findings suggest a predictive role for XRCC1 gene polymorphisms in clinical outcome. However, the role of 399Gln could be considered controversial because its impact on clinical outcome was insignificant in high-quality studies. These findings show the importance of establishing suitable criteria, including genetic epidemiologic, phenotypic, and clinical criteria, to improve quality control of study design and methods in pharmacogenomic studies related to XRCC1 gene polymorphism.

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Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum‐based chemotherapy in advanced nonsmall‐cell lung cancer patients

Peng

Zhang

et al. 2014

Intl Journal of Cancer

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Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum-based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p 5 0.005], while XRCC1 399 GA, or GA1AA, was associated with poor OS in short-term period (HR 1.718, p 5 0.003; HR 1.691, p 5 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short-term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA1AA) had higher risk of hematologic toxicity (p 5 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p 5 0.015 and p 5 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1-141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum-based chemotherapy.Lung cancer is the leading cause of cancer-related death in the world and in China. 1 Eighty percent of lung cancer patients are diagnosed with nonsmall-cell lung cancer (NSCLC), of which nearly two thirds are diagnosed at the advanced stages (such as stage IIIB or IV), 2 making curative surgery impossible. Currently, platinum-based therapy is the major remedial option for these advanced inoperable NSCLC patients. To determine the optimal regimen for platinumbased therapy, a randomized phase III clinical trial investigated the effects of four different combinations of cisplatin or carboplatin plus paclitaxel, docetaxel or gemcitabine on 1,207 advanced NSCLC patients, and the data showed that the efficacy of each combination was similar with response rates of 30-40%. 3 The therapeutic efficacy of platinum agents is limited by drug resistance and these advanced NSCLC patients have a 5-year survival rate of only 15%. 4,5 Thus, novel approaches are urgently needed for early detection, better chemotherapeutic agents, selection of more responsive patients for the particular chemotherapy and biomarkers to predict drug sensitivity and outcome.To this end, rapid advances in genomic study have provided novel technologies and therapeutic strategies to establish individualized chemotherapy regimens, which could maximize the benefits of chemotherapy and minimize the likelihood of drug toxicity by allowing the selection of each patient for optimal drug and dosages based on the molecular profiles of their tumors. One such study has focused on DNA repair genes and their polymorphisms in patients treated with platinum-based chemotherapies. This is because DNA repair capacity in tumor cells could lead to resistance of ...

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No association betweenXRCC1polymorphisms and survival in non-small-cell lung cancer patients treated with platinum-based chemotherapy

Cited by 13 publications

References 33 publications

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

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

Predictive Value of XRCC1 Gene Polymorphisms on Platinum-Based Chemotherapy in Advanced Non–Small Cell Lung Cancer Patients: A Systematic Review and Meta-analysis

Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum‐based chemotherapy in advanced nonsmall‐cell lung cancer patients

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