RGD Reference Report - The VEGFR2, COX-2 and MMP-2 polymorphisms are associated with clinical outcome of patients with inoperable non-small cell lung cancer. - Rat Genome Database

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The VEGFR2, COX-2 and MMP-2 polymorphisms are associated with clinical outcome of patients with inoperable non-small cell lung cancer.

Authors: Butkiewicz, Dorota  Krześniak, Małgorzata  Drosik, Anna  Giglok, Monika  Gdowicz-Kłosok, Agnieszka  Kosarewicz, Agata  Rusin, Marek  Masłyk, Barbara  Gawkowska-Suwińska, Marzena  Suwiński, Rafał 
Citation: Butkiewicz D, etal., Int J Cancer. 2015 Nov 15;137(10):2332-42. doi: 10.1002/ijc.29605. Epub 2015 Jun 3.
RGD ID: 126925198
Pubmed: PMID:25975224   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.29605   (Journal Full-text)

Certain common inherited variations in genes involved in tumor angiogenesis, progression and metastasis may contribute to cancer therapy outcome and prognosis by altering the gene expression and protein activity. In this report, we examined the effect of functional polymorphisms in MMP-1, MMP-2, MMP-3, VEGF, VEGFR2, FGFR4 and COX-2 genes on overall (OS) and progression-free survival (PFS) of 350 Caucasian patients with inoperable non-small cell lung cancer (NSCLC). The results of multivariate analysis indicated that VEGFR2 -906C and COX-2 -1195G alleles were strongly associated with poor OS and PFS (p = 0.002 and 0.015, respectively, for OS; p = 0.009 and 0.015, respectively, for PFS), while MMP-2 -1306 T allele carriers had significantly reduced PFS (p = 0.010). Moreover, an increased risk of death and progression was significantly associated with the number of adverse alleles for VEGFR2/COX-2 (p = 0.0005 for OS and 0.0006 for PFS in >1 adverse allele carriers) and VEGFR2/COX-2/MMP-2 combinations (p = 0.0003 for OS and 0.0001 for PFS in patients with >2 adverse alleles). Finally, VEGFR2 TC/CC, COX-2 AG/GG and MMP-2 CT/TT genotypes as well as "at risk" allele combinations were identified as independent predictors of unfavorable OS and PFS in the group. In conclusion, the data suggest that selected VEGFR2, COX-2 and MMP-2 polymorphisms may be potential prognostic markers in unresectable NSCLC treated with radiotherapy with or without chemotherapy, although further validation studies are warranted to confirm our observations.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung non-small cell carcinoma disease_progressionIAGP 126925198DNA:SNP:promoter:���906T>C (rs2071559) (human)RGD 
lung non-small cell carcinoma disease_progressionISOKDR (Homo sapiens)126925198; 126925198DNA:SNP:promoter:���906T>C (rs2071559) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdr  (kinase insert domain receptor)

Genes (Mus musculus)
Kdr  (kinase insert domain protein receptor)

Genes (Homo sapiens)
KDR  (kinase insert domain receptor)


Additional Information