Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer

Shuanghu Yuan, Vicki L. Ellingrod, Matthew Schipper, Kathleen A. Stringer, Xuwei Cai, James A. Hayman, Jinming Yu, Theodore S. Lawrence, Feng Ming Kong

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

INTRODUCTION: We hypothesized that radiation-induced thoracic toxicity (RITT) of the lung, esophagus and pericardium share a similar mechanism, and aimed to examine whether genetic variation of transforming growth factor-beta1 (TGFβ1), tissue plasminogen activator (tPA) and angiotensin converting enzyme (ACE), are associated with RITT in patients with non-small-cell lung cancer (NSCLC). METHODS: Patients with stage I-III NSCLC were enrolled and received radiotherapy (RT). Blood samples were obtained pre-RT and at 4 to 5 weeks during RT, and plasma TGF-β1 was measured using an enzyme-linked immunosorbent assay. The DNA samples extracted from blood pre-RT were analyzed for the following frequent genetic variations: TGFβ1 509C/T, tPA -7351 C/T, and ACE I/D. RITT score was defined as the sum of radiation-induced toxicity grades in esophagus, lung, and pericardium. RESULTS: Seventy-six NSCLC patients receiving definitive RT were enrolled. Patients with TGFβ1 509CC had higher mean grade of esophagitis (1.4 ± 0.2 versus 0.8 ± 0.2, p = 0.019) and RITT score (2.6 ± 0.3 versus 1.6 ± 0.3, p = 0.009) than T allele carriers. Although no significant relationship was observed between RITT and the tPA or ACE variants individually, patients with any high-risk alleles (tPA CC or ACE D or TGFβ1 509CC) had significantly higher grade of developing combined RITT (p < 0.001). Patients with TGFβ1 509CC had greater increase of plasma TGF β1 levels at 4 to 5 weeks during RT than T allele carriers did (CC 1.2 ± 0.2 versus T 0.7 ± 0.1, p = 0.047). CONCLUSION: This exploratory study demonstrated that sensitivity of radiation toxicity may be determined by genomic factors associated with TGFβ1 and genes involved in TGFβ1 pathway.

Original languageEnglish (US)
Pages (from-to)208-213
Number of pages6
JournalJournal of Thoracic Oncology
Volume8
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Non-small-cell lung cancer
  • Radiotherapy
  • Single nucleotide polymorphism
  • Toxicity

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Yuan, S., Ellingrod, V. L., Schipper, M., Stringer, K. A., Cai, X., Hayman, J. A., Yu, J., Lawrence, T. S., & Kong, F. M. (2013). Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer. Journal of Thoracic Oncology, 8(2), 208-213. https://doi.org/10.1097/JTO.0b013e318274592e