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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Single Nucleotide Polymorphism
Lung Neoplasms
Survival
Non-Small Cell Lung Carcinoma
Alleles
Luciferases
Real-Time Polymerase Chain Reaction
Research Design
Genotype
Confidence Intervals
Lung
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jeon, H. S., Jin, G., Kang, H. G., Choi, Y. Y., Lee, W. K., Choi, J. E., ... 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

A functional variant at 19q13.3, rs967591G>A, is associated with shorter survival of early-stage lung cancer. / Jeon, Hyo Sung; Jin, Guang; Kang, Hyo Gyoung; Choi, Yi Young; Lee, Won Kee; Choi, Jin Eun; Bae, Eun Young; Yoo, Seung Soo; Lee, Shin Yup; Lee, Eung Bae; Kim, Young Tae; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Jheon, Sanghoon; Kim, In-San; Park, Jae Yong.

In: Clinical Cancer Research, Vol. 19, No. 15, 01.08.2013, p. 4185-4195.

Research output: Contribution to journalArticle

Jeon, HS, Jin, G, Kang, HG, Choi, YY, Lee, WK, Choi, JE, Bae, EY, Yoo, SS, Lee, SY, Lee, EB, Kim, YT, Lee, J, Cha, SI, Kim, CH, Jheon, S, Kim, I-S & Park, JY 2013, 'A functional variant at 19q13.3, rs967591G>A, is associated with shorter survival of early-stage lung cancer', Clinical Cancer Research, vol. 19, no. 15, pp. 4185-4195. https://doi.org/10.1158/1078-0432.CCR-12-2792
Jeon, Hyo Sung ; Jin, Guang ; Kang, Hyo Gyoung ; Choi, Yi Young ; Lee, Won Kee ; Choi, Jin Eun ; Bae, Eun Young ; Yoo, Seung Soo ; Lee, Shin Yup ; Lee, Eung Bae ; Kim, Young Tae ; Lee, Jaehee ; Cha, Seung Ick ; Kim, Chang Ho ; Jheon, Sanghoon ; Kim, In-San ; Park, Jae Yong. / A functional variant at 19q13.3, rs967591G>A, is associated with shorter survival of early-stage lung cancer. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 15. pp. 4185-4195.
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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.",
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T1 - A functional variant at 19q13.3, rs967591G>A, is associated with shorter survival of early-stage lung cancer

AU - Jeon, Hyo Sung

AU - Jin, Guang

AU - Kang, Hyo Gyoung

AU - Choi, Yi Young

AU - Lee, Won Kee

AU - Choi, Jin Eun

AU - Bae, Eun Young

AU - Yoo, Seung Soo

AU - Lee, Shin Yup

AU - Lee, Eung Bae

AU - Kim, Young Tae

AU - Lee, Jaehee

AU - Cha, Seung Ick

AU - Kim, Chang Ho

AU - Jheon, Sanghoon

AU - Kim, In-San

AU - Park, Jae Yong

PY - 2013/8/1

Y1 - 2013/8/1

N2 - 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.

AB - 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.

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