Genomic profiling as predictor of toxicity in patients with advanced colorectal cancer treated with platinum-based chemotherapy

Park, D. J.; Yun, Jie; Yang, Dongyun; Iqbal, Syma; Press, O.; Groshen, Susan; Gordon, Michael A.; Zhang, W.; Lenz, H.

doi:10.1200/jco.2004.22.14_suppl.3627

Cited by 20 publications

(31 citation statements)

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“…ERCC1 8092C/A has been found to have positive associations in breast cancer risk [38,39], glioma risk [40], and a gene-smoking interaction in lung cancer risk [41]. The ERCC1 118C/ T was mostly found to be associated with predicting outcome in treated patients with various types of cancer, including colon cancer [42,43]. Other studies in lung cancer found ERCC1 118C/T to be nonsignificant in predicting outcome in treated lung cancer patients [44,45].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Tse

Zhai

Zhou

et al. 2008

Cancer Causes Control

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Purpose-Functional variation in DNA repair capacity through single nucleotide polymorphisms (SNPs) of key repair genes is associated with a higher risk of developing various types of cancer. Studies have focused on the nucleotide excision repair (NER) and base excision repair (BER) pathways. We investigated whether variant alleles in seven SNPs within these pathways increased the risk of esophageal adenocarcinoma. NIH Public Access Author ManuscriptCancer Causes Control. Author manuscript; available in PMC 2011 June 1. Results-Variant alleles in NER SNPs XPD Lys751Gln (AOR = 1.50, 95% CI 1.1-2.0), ERCC1 8092 C/A (AOR = 1.44, 95% CI 1.1-1.9), and ERCC1 118C/T (AOR = 1.42, 95% CI 1.0-1.9) were individually associated with esophageal adenocarcinoma risk. An increasing number of variant alleles in NER SNPs showed a significant trend with esophageal adenocarcinoma risk (p = 0.007).Conclusions-The presence of variant alleles in NER genes increases risk of esophageal adenocarcinoma. There is evidence of an additive role for SNPs along a common DNA repair pathway. Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Tse

Zhai

Zhou

et al. 2008

Cancer Causes Control

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“…Recently, it was noted that the codon 118 C/T polymorphism (rs11615) is associated with differential mRNA levels (Yu et al, 2000;Park et al, 2003) and has been found to be associated with shorter overall survival for advanced colorectal cancer patients treated with platinum-based chemotherapy (Park et al, 2003). So, we hypothesized that this polymorphism in ERCC1 might affect the platinum-resistance of EOC patients.…”

Section: Introductionmentioning

confidence: 95%

Association between excision repair cross-complementation group 1 polymorphism and clinical outcome of platinum-based chemotherapy in patients with epithelial ovarian cancer

Kang

Ju²,

Kim³

et al. 2006

Exp Mol Med

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ERCC1 is a DNA repair gene and has been associated with resistance to DNA damaging agents. In this study we hypothesized that a polymorphism of ERCC1 Asn118Asn (C→T) might affect the platinum-resistance of epithelial ovarian cancer patients to platinum-taxane chemotherapy administered postoperatively. Using the SNapShot assay, we assessed this polymorphism in ERCC1 in 60 ovarian cancer patients. Platinum-resistance was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. Although not significant, platinum-resistance was less frequently observed in patients with the C/T + T/T genotype (P = 0.064). Multivariate analysis showed that the C/T + T/T genotypes constituted an independent predictive factor of reduced risk of platinum-resistance in ovarian cancer (odds ratio 0.17, 95% confidence interval 0.04-0.74, P = 0.018, Fisher's exact test). No significant correlation was observed between overall survival and the ERCC1 polymorphism. Our results suggest that genotyping of the ERCC1 polymorphism Asn118Asn may be useful for predicting the platinum-resistance of epithelial ovarian cancer patients. However, these findings require prospective confirmation.

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“…Besides the latter, none of these SNPs showed a (borderline) significant association with PFS or OS in the current univariate analysis. Various studies in colorectal cancer (Park et al, 2003;Stoehlmacher et al, 2004;Viguier et al, 2005;Ruzzo et al, 2007) and lung cancer patients (Su et al, 2007) suggest that the ERCC1 118CC genotype is associated with longer OS and a better response towards platinum agents. Another study reports no association of this SNP with OS , but a significantly worse OS was found for patients carrying X1 mutant allele of the other ERCC1 SNP, C8092A.…”

Section: Discussionmentioning

confidence: 99%

Explorative study to identify novel candidate genes related to oxaliplatin efficacy and toxicity using a DNA repair array

et al. 2009

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PURPOSE: To identify new polymorphisms (single nucleotide polymorphisms, SNPs) in DNA repair pathways that are associated with efficacy and toxicity in patients receiving oxaliplatin and capecitabine for advanced colorectal cancer (ACC). METHODS: We studied progression-free survival (PFS) in 91 ACC patients, of whom germ-line DNA was isolated and genotyped using an Asper Biotech array. Overall survival (OS) and toxicity were studied as secondary end points. A step-wise selection of SNPs was performed, involving univariate and multivariate log-rank tests and Cox regression analysis, with age and performance status as covariates. RESULTS: A total of 81 SNPs in 46 genes on the array were selected for further analysis, based on genotyping success rates and minor allele frequencies. After step-wise selection, we found that homozygosity for the ataxia telangiectasia mutated gene (ATM) rs1801516 or excision repair cross-complementing gene (ERCC5) rs1047768 SNPs was associated with shorter PFS; however there were no significant associations (P40.01) with OS or toxicity. DISCUSSION: This is the first study describing the pathway gene approach for the selection of new candidate genes involved in oxaliplatin efficacy and toxicity. The results suggest that the ATM and ERCC5 genes may be associated with oxaliplatin efficacy in ACC.

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Genomic profiling as predictor of toxicity in patients with advanced colorectal cancer treated with platinum-based chemotherapy

Cited by 20 publications

References 0 publications

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Association between excision repair cross-complementation group 1 polymorphism and clinical outcome of platinum-based chemotherapy in patients with epithelial ovarian cancer

Explorative study to identify novel candidate genes related to oxaliplatin efficacy and toxicity using a DNA repair array

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