Genomic Profiling Associated with Recurrence in Patients with Rectal Cancer Treated with Chemoradiation

Gordon, Michael A.; Gil, Ji; Lü, Bo; Zhang, Wu; Yang, Dongyun; Yun, Jim; Schneider, Sylke; Groshen, Susan; Iqbal, Syma; Press, O.; Rhodes, Katrin E.; Lenz, Heinz‐Josef

doi:10.2217/14622416.7.1.67

Cited by 51 publications

(39 citation statements)

References 40 publications

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“…Li et al (2006) analyzed pancreatic cancer treated with radiotherapy and did not find any association between this polymorphism and survival. Likewise, Gordon et al (2006) studied rectal cancer and did not report an association of this polymorphism with disease relapse, lymph node status or chemotherapy response, which concurs with our results. We found that the C allele is associated with worse prognosis, but this is not related to radiotherapy.…”

Section: Discussionsupporting

confidence: 90%

Prognostic significance of head and neck squamous cell carcinoma repair gene polymorphism

et al. 2015

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ABSTRACT. The aims of this study were to analyze the polymorphisms XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPC Lys939Gln, ERCC1 Asn118Asn, and RAD51 -98G>C and to verify their influence on radiotherapy response and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). Peripheral blood DNA was extracted from 311 patients and analyzed by PCR-RFLP. Our results showed that in irradiated oral and oropharyngeal patients, the 939Gln allele increased 6-fold local disease relapse risk (OR = 6.04; CI = 1.47-24.88) and over 2-fold the earliness of relapse (HR = 2.63; CI = 1.04-6.70). As for the XRCC3 polymorphism, multivariate analysis showed that the 241Met allele increases over 33-fold local relapse risk (OR = 33.64; CI = 3.23-350.85), over 12-fold earliness of relapse (HR = 12.55; CI = 2.47-63.73) and over 3-fold earliness of death (HR = 3.04; CI = 1.08-8.61). For polymorphism RAD51 -98, multivariate analysis showed that allele C increases over 3-fold the risk of relapse (OR = 3.13; CI = 1.12-8.78) and over 2-fold the earliness of relapse (HR = 2.84; CI = 1.25-6.47). For polymorphism XRCC1 Arg399Gln, multivariate analysis showed that the 399Gln allele increased the risk of local disease relapse for irradiated oral and oropharyngeal patients (OR = 3.35; CI = 1.10-10.13) by over 3-fold. Based on these results, we suggest that these polymorphisms may be useful markers of prognosis in HNSCC.

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Section: Discussionsupporting

confidence: 90%

Prognostic significance of head and neck squamous cell carcinoma repair gene polymorphism

et al. 2015

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“…Our previous data and others have shown that the IL-8/CXCR2 pathway plays a key role in mediating colorectal cancer development (11,14,15,32). In follow-up to our previously published data in colorectal cancer, this study focused on the impact of inhibition of CXCR2 on the proliferation, survival, invasion, and migration in colorectal cancer in vitro and in vivo models.…”

Section: Discussionmentioning

confidence: 90%

The CXCR2 Antagonist, SCH-527123, Shows Antitumor Activity and Sensitizes Cells to Oxaliplatin in Preclinical Colon Cancer Models

Ning

LaBonte

Zhang

et al. 2012

Molecular Cancer Therapeutics

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Colorectal cancer is the second most common cause of cancer-related death in the United States. Recent studies showed that interleukin-8 (IL-8) and its receptors (CXCR1 and CXCR2) are significantly upregulated in both the tumor and its microenvironment, and act as key regulators of proliferation, angiogenesis, and metastasis. Our previous study showed that IL-8 overexpression in colorectal cancer cells triggers the upregulation of the CXCR2-mediated proliferative pathway. The aim of this study was to investigate whether the CXCR2 antagonist, SCH-527123, inhibits colorectal cancer proliferation and if it can sensitize colorectal cancer cells to oxaliplatin both in vitro and in vivo. SCH-527123 showed concentration-dependent antiproliferative effects in HCT116, Caco2, and their respective IL-8-overexpressing variants colorectal cancer cell lines. Moreover, SCH-527123 was able to suppress CXCR2-mediated signal transduction as shown through decreased phosphorylation of the NF-kB/mitogen-activated protein kinase (MAPK)/AKT pathway. These findings corresponded with decreased cell migration and invasion, while increased apoptosis in colorectal cancer cell lines. In vivo results verified that SCH-527123 treatment decreased tumor growth and microvessel density when compared with vehicle-treated tumors. Importantly, these preclinical studies showed that the combination of SCH-527123 and oxaliplatin resulted in a greater decrease in cell proliferation, tumor growth, apoptosis, and angiogenesis that was superior to single-agent treatment. Taken together, these findings suggest that targeting CXCR2 may block tumor proliferation, migration, invasion, and angiogenesis. In addition, CXCR2 blockade may further sensitize colorectal cancer to oxaliplatin treatment.

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“…Although the detail mechanisms for individual difference in radiotherapy remained unknown, genetic polymorphisms were demonstrated to be one of the major factors influencing the radiotherapy, especially the genetic polymorphisms of DNA repair genes (Gordon et al, 2006;Terrazzino et al, 2006). DNA damage response plays a significant role in the biological effects of radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

Guo

Yang²,

Pei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: : A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

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Genomic Profiling Associated with Recurrence in Patients with Rectal Cancer Treated with Chemoradiation

Cited by 51 publications

References 40 publications

Prognostic significance of head and neck squamous cell carcinoma repair gene polymorphism

Prognostic significance of head and neck squamous cell carcinoma repair gene polymorphism

The CXCR2 Antagonist, SCH-527123, Shows Antitumor Activity and Sensitizes Cells to Oxaliplatin in Preclinical Colon Cancer Models

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

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