| MGMT -535G>T polymorphism is associated with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy. | |
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MedLine Citation:
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PMID: 20091185 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer. PATIENTS AND METHODS: A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR-RFLP assay. RESULTS: During the median follow-up duration of 15.9 (2.1-53.0) months, 67 (71.3%) progressions and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) -535G>T polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG + GT genotypes (HR = 3.137; 95% CI = 1.423-6.914; P = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101-6.392; P = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (HR = 0.229 and 0.205; P < 0.001 and 0.001, respectively). CONCLUSION: The MGMT -535G>T polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy. |
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Authors:
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Jee Hyun Park; Nung Soo Kim; Jae Yong Park; Yee Soo Chae; Jong Gwang Kim; Sang Kyun Sohn; Joon Ho Moon; Byung Woog Kang; Hun Mo Ryoo; Sung Hwa Bae; Gyu Seog Choi; Soo-Han Jun |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-21 |
Journal Detail:
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Title: Journal of cancer research and clinical oncology Volume: 136 ISSN: 1432-1335 ISO Abbreviation: J. Cancer Res. Clin. Oncol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-06-21 Completed Date: 2010-07-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902060 Medline TA: J Cancer Res Clin Oncol Country: Germany |
Other Details:
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Languages: eng Pagination: 1135-42 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution
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genetics Antineoplastic Agents / therapeutic use* Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Chromosome Mapping Colonic Neoplasms / genetics, pathology Colorectal Neoplasms / drug therapy*, pathology* DNA Modification Methylases / genetics* DNA Repair / genetics* DNA Repair Enzymes / genetics* Deoxycytidine / analogs & derivatives, therapeutic use Female Fluorouracil / analogs & derivatives, therapeutic use Genotype Humans Male Middle Aged Neoplasm Metastasis / genetics Organoplatinum Compounds / therapeutic use* Polymorphism, Genetic Polymorphism, Single Nucleotide* Prognosis Rectal Neoplasms / genetics, pathology Tumor Suppressor Proteins / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Organoplatinum Compounds; 0/Tumor Suppressor Proteins; 0/XELOX; 51-21-8/Fluorouracil; 63121-00-6/oxaliplatin; 951-77-9/Deoxycytidine; EC 2.1.1.-/DNA Modification Methylases; EC 2.1.1.63/MGMT protein, human; EC 6.5.1.-/DNA Repair Enzymes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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