NDLI: The single nucleotide polymorphism g.1548A >G (K469E) of the ICAM-1 gene is associated with worse prognosis in non-small cell lung cancer.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Thanopoulou, Eirini Kotzamanis, George Pateras, Ioannis S. Ziras, Nicholaos Papalambros, Alexandros Mariolis-Sapsakos, Theodoros Sigala, Fragiska Johnson, Elizabeth Kotsinas, Athanassios Scorilas, Andreas Gorgoulis, Vassilis G.
Description	Country affiliation: Greece Author Affiliation: Thanopoulou E ( Department of Histology and Embryology, School of Medicine, University of Athens, 75 Mikras Asias Str, Goudi, Athens, GR-11527, Greece.)
Abstract	Intercellular adhesion molecule-1 (ICAM-1), a cell adhesion molecule with a key role in inflammation and immunosurveillance, has been implicated in carcinogenesis by facilitating instability of the tumor environment. The K469E single nucleotide polymorphism (SNP) (G>A) affects the ICAM-1 mRNA splicing pattern; the alternatively spliced isoform (ICAM-1-S) lacks transmembrane and intracellular domain, which affects the structural and signal transduction properties. Moreover, the expression of ICAM-1 is transcriptionally regulated by p53, and this SNP has been shown to be related with apoptosis. PCR-RFLP analysis was used to assess the K469E SNP status comparatively in 203 non-small cell lung cancer patients and 175 healthy sex-matched controls. This SNP was examined in relation to tumor kinetic parameters (Ki-67 immunohistochemical evaluation and Tdt-mediated dUTP nick end labeling assay), p53 immunohistochemistry status, and clinicopathological data in patients with operable stages. Both the genotype and allele frequency did not differ significantly between patients and controls. However, patients with the AG/AA genotypes had worse survival (39 vs 45 months, p = 0.036) and tended to be present in advanced stages (p = 0.057). Moreover, the AG/AA genotypes exerted a synergistic effect with aberrant p53 on tumor progression, while the GG genotype retained a better apoptotic index. The AG/AA genotypes correlated with worse survival and advanced stages probably due to defective immunosurveillance and apoptosis. These genetic backgrounds may confer a selective advantage for dissemination of tumor cells with high metastatic potential compared to GG genotype.
File Format	HTM / HTML
ISSN	10104283
Issue Number	5
Volume Number	33
e-ISSN	14230380
Journal	Tumor Biology
Language	English
Publisher	Springer
Publisher Date	2012-10-01
Publisher Place	Netherlands
Access Restriction	Subscribed
Subject Keyword	Discipline Medicine__semicolon__oncology Carcinoma, Non-small-cell Lung Genetics Mortality Intercellular Adhesion Molecule-1 Lung Neoplasms Polymorphism, Single Nucleotide Adult Aged Aged, 80 And Over Alleles Pathology Case-control Studies Disease Progression Female Gene Frequency Genotype Humans Male Middle Aged Neoplasm Staging Prognosis Tumor Suppressor Protein P53 Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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