In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 19, No. 15 ( 2013-08-01), p. 4185-4195
Kurzfassung:
Purpose: This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) in 19q13.3 and survival of patients with early-stage non–small cell lung cancer (NSCLC), and to define the causative functional SNP of the association. Experimental Design: A two-stage study design was used to evaluate five SNPs in relation to survival outcomes in 328 patients and then to validate the results in an independent patient population (n = 483). Luciferase assay and real-time PCR were conducted to examine functional relevance of a potentially functional SNP. Results: Of the five SNPs, three SNPs (rs105165C & gt;T, rs967591G & gt;A, and rs735482A & gt;C) were significantly associated with survival outcomes in a stage I study. The rs967591A allele had significantly higher activity of the CD3EAP promoter compared with the rs967591G allele (P = 0.002), but the SNP did not have an effect on the activity of PPP1R13L promoter. The rs967591G & gt;A was associated with the level of CD3EAP mRNA expression in lung tissues (P = 0.01). The rs967591G & gt;A exhibited consistent associations in a stage II study. In combined analysis, the rs967591 AA genotype exhibited a worse overall survival (adjusted HR = 1.69; 95% confidence interval = 1.29–2.20; P = 0.0001). Conclusion: The rs967591G & gt;A affects CD3EAP expression and thus influences survival in early-stage NSCLC. The analysis of the rs967591G & gt;A polymorphism can help identify patients at high risk of a poor disease outcome. Clin Cancer Res; 19(15); 4185–95. ©2013 AACR.
Materialart:
Online-Ressource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-12-2792
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2013
ZDB Id:
1225457-5
ZDB Id:
2036787-9
