title: The VEGFR2, COX-2 and MMP-2 polymorphisms are associated with clinical outcome of patients with inoperable non-small cell lung cancer.
abstract: 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.
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krześniak
authors.affiliation: II Clinic of Radiotherapy and Chemotherapy, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.|Department of Clinical Oncology, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Drosik
authors.affiliation: II Clinic of Radiotherapy and Chemotherapy, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Giglok
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gdowicz-Kłosok
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Kosarewicz
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Rusin
authors.affiliation: Department of Analytics and Clinical Biochemistry, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Masłyk
authors.affiliation: III Clinic of Radiotherapy and Chemotherapy, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Gawkowska-Suwińska
authors.affiliation: II Clinic of Radiotherapy and Chemotherapy, M. Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Suwiński
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: COX-2; MMP; VEGFR2; lung cancer; polymorphism; radiotherapy; survival