Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab

Koutras, A.; Ag, Antonacopoulou; Eleftheraki, Anastasia G; Dimitrakopoulos, Foteinos-Ioannis; Koumarianou, Anna; Varthalitis, Ioannis; Fostira, Florentia; Sgouros, Joseph; Briasoulis, Evangelos; Bournakis, Evangelos; Bafaloukos, Dimitrios; Bompolaki, Iliada; Galani, Eleni; Kalogeras, K. T.; Pectasides, Dimitrios; Fountzilas, George; Kalofonos, Haralabos P.

doi:10.1038/tpj.2011.37

Cited by 60 publications

(39 citation statements)

References 30 publications

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“…A number of authors reported that VEGF −1154 G>A allele frequencies analyzed in blood samples were G/G in about 45%–50% of cases, G/A in 35%–40% and A/A in 10%–15% [17,18,19,20], in agreement with our results. Conversely, in FFPE tumor tissue, we observed higher frequencies of patients homozygous for the A-allele.…”

Section: Resultssupporting

confidence: 93%

Discrepancies between VEGF −1154 G>A Polymorphism Analysis Performed in Peripheral Blood Samples and FFPE Tissue

Marisi

Passardi

Calistri

et al. 2014

IJMS

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Single nucleotide polymorphisms (SNPs) may be associated with the response or toxicity to different types of treatment. Although SNP analysis is usually performed on DNA from peripheral blood, formalin fixed paraffin-embedded (FFPE) tissue is often used for retrospective studies. We analyzed VEGF (−2578C>A, −1498C>T, −1154G>A, −634C>G, +936C>T) and eNOS (+894G>T, −786T>C, VNTR (variable number of tandem repeats) 27bp intron 4) polymorphisms by direct sequencing or Real Time PCR in 237 patients with advanced colorectal cancer. Peripheral blood was used for 153 patients, whereas only FFPE tumor tissue was available for 84 patients. All SNP frequencies were in Hardy-Weinberg Equilibrium (HWE), with the exception of VEGF −1154, which was only in HWE in peripheral blood specimens. We therefore analyzed this SNP in DNA extracted from FFPE tumor tissue compared to FFPE healthy tissue and peripheral blood from 20 patients. Numerous heterozygous patients in peripheral blood DNA were homozygous for the A-allele in both tumor and healthy FFPE tissues. Our findings indicate that, although FFPE tissue might be a suitable specimen for genotyping, VEGF −1154 does not give reliable results on this type of material. As other SNPs may also have this limitation, genotype concordance should first be confirmed by comparing results obtained from FFPE and fresh sample analyses.

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Section: Resultssupporting

confidence: 93%

Discrepancies between VEGF −1154 G>A Polymorphism Analysis Performed in Peripheral Blood Samples and FFPE Tissue

Marisi

Passardi

Calistri

et al. 2014

IJMS

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“…The results of this study differ from those of previous studies, which demonstrated the association between VEGFA polymorphisms and the patients' outcomes [14,29,30]. Several studies showed that the elevated baseline VEGF concentration correlated with poor outcomes [15,31,32].…”

Section: Discussioncontrasting

confidence: 99%

“…Schultheis et al [14] reported that patients with the VEGFA rs3025039 C/T genotype had a longer median PFS compared to those with the C/C and T/T genotypes in recurrent ovarian cancer. Furthermore, Koutras et al [30] showed that the VEGFA rs1570360 G/G genotype remained an adverse factor for OS but not for PFS in metastatic CRC patients treated with irinotecan-based chemotherapy. However, the association of VEGFA polymorphisms with patients' outcomes was not consistent in several tumor types, and the confidence of its association for patients' prognosis has been less than clear until recently.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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.

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“…Recently, we showed that the VEGF-1154 GG genotype was associated with significantly shorter OS in patients with colorectal cancer receiving irinotecan-containing chemotherapy plus bevacizumab [61]. Moreover, the VEGF-1154 GG genotype was more frequent in patients not responding to treatment compared with responders.…”

Section: Predictive Factorsmentioning

confidence: 96%

Angiogenesis as a therapeutic target in breast cancer

Koutras¹,

Starakis²,

Lymperatou³

et al. 2012

MRMC

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Current evidence indicates that angiogenesis plays an important role in the pathogenesis of several malignancies, including breast cancer. Bevacizumab is a monoclonal antibody that targets the vascular endothelial growth factor (VEGF). Recent clinical data have demonstrated that the addition of bevacizumab to first-line chemotherapy improves the progression-free survival of patients with advanced breast cancer. This review presents an update on the role of bevacizumab, as well as other anti-angiogenic agents in the management of patients with breast carcinoma.

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Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab

Cited by 60 publications

References 30 publications

Discrepancies between VEGF −1154 G>A Polymorphism Analysis Performed in Peripheral Blood Samples and FFPE Tissue

Discrepancies between VEGF −1154 G>A Polymorphism Analysis Performed in Peripheral Blood Samples and FFPE Tissue

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

Angiogenesis as a therapeutic target in breast cancer

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