Single-Nucleotide Polymorphisms in the Vascular Endothelial Growth Factor Pathway and Outcomes of Patients Treated with First-Line Cytotoxic Chemotherapy Combined with Bevacizumab for Advanced Colorectal Cancer
| Autor: | Cheolwon Suh, Young Suk Park, Byeong Seok Sohn, Joong Bae Ahn, Sun-Young Kim, Seock-Ah Im, Jeong Eun Kim, Jee Hyun Kim, Kyu Pyo Kim, Yong Sang Hong, Seon-Young Kim, Tae Won Kim, Yong Sung Kim, Seong Joon Park |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Oncology Cancer Research medicine.medical_specialty Genotype Bevacizumab Colorectal cancer Single-nucleotide polymorphism Antibodies Monoclonal Humanized Polymorphism Single Nucleotide chemistry.chemical_compound Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Vascular Endothelial Growth Factor Receptor-1 business.industry Haplotype Kinase insert domain receptor General Medicine medicine.disease Vascular endothelial growth factor Vascular endothelial growth factor A Haplotypes chemistry Female Colorectal Neoplasms business medicine.drug |
| Zdroj: | Oncology. 87:280-292 |
| ISSN: | 1423-0232 0030-2414 |
| Popis: | Objective: The aim of this study was to evaluate the association between the efficacy of first-line cytotoxic chemotherapy plus bevacizumab and single-nucleotide polymorphisms (SNPs) of angiogenic genes in patients with advanced colorectal cancer (CRC). Methods: DNA was extracted from blood samples of 125 patients, and 12 SNPs were evaluated for association with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: The vascular endothelial growth factor A (VEGFA) rs833061 T/T was associated with superior ORR compared to its alternative genotypes (75.9 vs. 50.8%; p = 0.008), and the interleukin 8 rs4073 A/A genotype tended to be associated with poor ORR (45.0 vs. 66.0%; p = 0.067). The median PFS and OS were superior in patients with the fms-related tyrosine kinase 1 (FLT1) rs9513070 A/A genotype (8.7 vs. 6.6 months; p = 0.001 and 26.4 vs. 16.1 months; p = 0.038, respectively). The kinase insert domain receptor rs1531289 G/G genotype tended to be associated with improved PFS (8.0 vs. 7.1 months; p = 0.069). In haplotype analysis, the FLT1 rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and OS (p = 0.004 and p = 0.041, respectively). Conclusion: The VEGFA rs833061 SNP is associated with the ORR, and the FLT1 rs9513070 SNP and FLT1 GCA haplotypes are associated with PFS and OS in advanced CRC patients treated with cytotoxic chemotherapy plus bevacizumab. |
| Databáze: | OpenAIRE |
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