Associations between oxaliplatin-induced peripheral neuropathy and polymorphisms of the ERCC1 and GSTP1 genes

Inada, Megumi; Sato, Mika; Morita, Sachi; Kitagawa, Kakuya; Kawada, Kei; Mitsuma, Ayako; Sawaki, Masataka; Fujita, Ken‐ichi; Ando, Yuichi

doi:10.5414/cpp48729

Cited by 59 publications

(27 citation statements)

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“…After reviewing the full text, 3 literatures were excluded, of which the data of two studies were inestimable and the authors were unreachable (Braun et al, 2008;Lamas et al, 2011), and patients in another additional study were treated with radiotherapy (Fakih et al, 2008). As a result, a total of 2846 CRC patients were enrolled in the 22 studies (Stoehlmacher et al, 2004;Viguier et al, 2005;Ruzzo et al, 2007;Liang et al, 2008;Martinez-Balibrea et al, 2008;Pare et al, 2008;Chang et al, 2009;Chua et al, 2009;Boige et al, 2010;Chen et al, 2010;Inada et al, 2010;Liang et al, 2010;Spindler et al, 2010;Farina Sarasqueta et al, 2011;Huang et al, 2011;Chai et al, 2012;Li et al, 2012;Cortejoso et al, 2013;Kumamoto et al, 2013;Lee et al, 2013;Nishina et al, 2013;Oguri et al, 2013) included in the pool-analysis. The selection procedure is shown in Figure 1 and the key patient characteristics are listed by study in Table1.…”

Section: Search Results and Study Selectionmentioning

confidence: 99%

The ERCC1 C118T Polymorphism Predicts Clinical Outcomes of Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Meta-analysis Based on 22 Studies

Qian¹,

Liu²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

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Section: Search Results and Study Selectionmentioning

confidence: 99%

The ERCC1 C118T Polymorphism Predicts Clinical Outcomes of Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Meta-analysis Based on 22 Studies

Qian¹,

Liu²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…These include genetic risk factors that alter sensitivity to cytotoxic effects, cellular repair mechanisms, and excitability of sensory neurons. For example, polymorphisms that alter the expression of the DNA excision repair protein ERCC-1 (excision repair cross-complementing group 1) have been suggested to be involved in cisplatin- and oxaliplatin-induced cytotoxicity, though no clinical study to date has shown an association with CIPN (Inada et al, 2010). Genetic variants of alanine glyoxylate aminotransferase (AGXT), an enzyme involved in oxalate metabolism, have been correlated with the severity of oxaliplatin-induced CIPN (Gamelin et al, 2007).…”

Section: The Genetics Of Chemotherapy-induced Peripheral Neuropathymentioning

confidence: 99%

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

Starobova

Vetter

2017

Front. Mol. Neurosci.

429

400

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Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

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“…Lee et al 20 found CRC patients with the T/T genotype to have a higher risk of neutropenia, and the C/T or T/T genotypes have been associated with oxaliplatin-induced neurotoxicity. 21 Detoxification of platinum-DNA adducts such as oxaliplatin is catalysed by glutathione-S-transferases. Once inside the cell, conjugation to glutathione inactivates the platinum compounds followed by cellular excretion of the conjugate, thereby protecting DNA from damage.…”

Section: Introductionmentioning

confidence: 99%

AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin

et al. 2015

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The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.

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Associations between oxaliplatin-induced peripheral neuropathy and polymorphisms of the ERCC1 and GSTP1 genes

Cited by 59 publications

References 0 publications

The ERCC1 C118T Polymorphism Predicts Clinical Outcomes of Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Meta-analysis Based on 22 Studies

The ERCC1 C118T Polymorphism Predicts Clinical Outcomes of Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Meta-analysis Based on 22 Studies

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin

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