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TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy.

Publication ,  Journal Article
Yuan, X; Wei, Q; Komaki, R; Liu, Z; Yang, J; Tucker, SL; Xu, T; Heymach, JV; Lu, C; Cox, JD; Liao, Z
Published in: PLoS One
2013

PURPOSE: Transforming growth factor (TGF) -β1 signaling is involved in cancer-cell metastasis. We investigated whether single nucleotide polymorphisms (SNPs) at TGFβ1 were associated with overall survival (OS) and distant metastasis-free survival (DMFS) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy, with or without chemotherapy. METHODS: We genotyped TGFβ1 SNPs at rs1800469 (C-509T), rs1800471 (G915C), and rs1982073 (T+29C) by polymerase chain reaction-restriction fragment length polymorphism in blood samples from 205 NSCLC patients who had had definitive radiotherapy at one institution in November 1998-January 2005. We also tested whether the TGF-β1 rs1982073 (T+29C) SNP affected the migration and invasion of A549 and PC9 lung cancer cells. RESULTS: Median follow-up time for all patients was 17 months (range, 1-97 months; 39 months for patients alive at the time of analysis). Multivariate analysis showed that the TGFβ1 rs1800469 CT/CC genotype was associated with poor OS (hazard ratio [HR] = 1.463 [95% confidence interval {CI} = 1.012-2.114], P = 0.043) and shorter DMFS (HR = 1.601 [95% CI = 1.042-2.459], P = 0.032) and that the TGFβ1 rs1982073 CT/CC genotype predicted poor DMFS (HR = 1.589 [95% CI = 1.009-2.502], P = 0.046) and poor brain MFS (HR = 2.567 [95% CI = 1.155-5.702], P = 0.021) after adjustment for age, sex, race, performance status, smoking status, tumor histology and volume, stage, receipt of concurrent radiochemotherapy, number of chemotherapy cycles, and radiation dose. Transfection with TGFβ1+29C (vs. +29T) stimulated the migration and invasion of A549 and PC9 cells, suggesting that TGFβ1+29C may be linked with increased metastatic potential. CONCLUSIONS: TGFβ1 genotypes at rs1800469 and rs1982073 could be useful for predicting DMFS among patients with NSCLC treated with definitive radiation therapy. These findings require validation in larger prospective trials and thorough mechanistic studies.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

6

Start / End Page

e65659

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Survival Analysis
  • Prospective Studies
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Neoplasm Metastasis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Yuan, X., Wei, Q., Komaki, R., Liu, Z., Yang, J., Tucker, S. L., … Liao, Z. (2013). TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy. PLoS One, 8(6), e65659. https://doi.org/10.1371/journal.pone.0065659
Yuan, Xianglin, Qingyi Wei, Ritsuko Komaki, Zhensheng Liu, Ju Yang, Susan L. Tucker, Ting Xu, et al. “TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy.PLoS One 8, no. 6 (2013): e65659. https://doi.org/10.1371/journal.pone.0065659.
Yuan, Xianglin, et al. “TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy.PLoS One, vol. 8, no. 6, 2013, p. e65659. Pubmed, doi:10.1371/journal.pone.0065659.
Yuan X, Wei Q, Komaki R, Liu Z, Yang J, Tucker SL, Xu T, Heymach JV, Lu C, Cox JD, Liao Z. TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy. PLoS One. 2013;8(6):e65659.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

6

Start / End Page

e65659

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Survival Analysis
  • Prospective Studies
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Neoplasm Metastasis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Humans