A functional variant at 19q13.3, rs967591G>A, is associated with shorter survival of early-stage lung cancer

Hyo Sung Jeon, Guang Jin, Hyo Gyoung Kang, Yi Young Choi, Won Kee Lee, Jin Eun Choi, Eun Young Bae, Seung Soo Yoo, Shin Yup Lee, Eung Bae Lee, Young Tae Kim, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Sanghoon Jheon, In San Kim, Jae Yong Park

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12 Citations (Scopus)

Abstract

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 (rs105165CT, rs967591GA, and rs735482AC) 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 rs967591GA was associated with the level of CD3EAP mRNAexpression in lung tissues (P=0.01). The rs967591GA 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 rs967591GA affects CD3EAP expression and thus influences survival in early-stage NSCLC. The analysis of the rs967591GA polymorphism can help identify patients at high risk of a poor disease outcome.

Original languageEnglish
Pages (from-to)4185-4195
Number of pages11
JournalClinical Cancer Research
Volume19
Issue number15
DOIs
Publication statusPublished - 2013 Aug 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Jeon, H. S., Jin, G., Kang, H. G., Choi, Y. Y., Lee, W. K., Choi, J. E., Bae, E. Y., Yoo, S. S., Lee, S. Y., Lee, E. B., Kim, Y. T., Lee, J., Cha, S. I., Kim, C. H., Jheon, S., Kim, I. S., & Park, J. Y. (2013). A functional variant at 19q13.3, rs967591G>A, is associated with shorter survival of early-stage lung cancer. Clinical Cancer Research, 19(15), 4185-4195. https://doi.org/10.1158/1078-0432.CCR-12-2792