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 Citations (Scopus)

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

Fingerprint

Transforming Growth Factor beta1
Tissue Plasminogen Activator
Peptidyl-Dipeptidase A
Non-Small Cell Lung Carcinoma
Thorax
Radiation
Radiotherapy
Pericardium
Alleles
Esophagus
Lung
Esophagitis
Radiation Tolerance
Enzyme-Linked Immunosorbent Assay
DNA
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer. / Yuan, Shuanghu; Ellingrod, Vicki L.; Schipper, Matthew; Stringer, Kathleen A.; Cai, Xuwei; Hayman, James A.; Yu, Jinming; Lawrence, Theodore S.; Kong, Feng Ming.

In: Journal of Thoracic Oncology, Vol. 8, No. 2, 02.2013, p. 208-213.

Research output: Contribution to journalArticle

Yuan, S, Ellingrod, VL, Schipper, M, Stringer, KA, Cai, X, Hayman, JA, Yu, J, Lawrence, TS & Kong, FM 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, vol. 8, no. 2, pp. 208-213. https://doi.org/10.1097/JTO.0b013e318274592e
Yuan, Shuanghu ; Ellingrod, Vicki L. ; Schipper, Matthew ; Stringer, Kathleen A. ; Cai, Xuwei ; Hayman, James A. ; Yu, Jinming ; Lawrence, Theodore S. ; Kong, Feng Ming. / Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer. In: Journal of Thoracic Oncology. 2013 ; Vol. 8, No. 2. pp. 208-213.
@article{2550de5d2a6f4db3b27f10a2299e8c2d,
title = "Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer",
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.",
keywords = "Non-small-cell lung cancer, Radiotherapy, Single nucleotide polymorphism, Toxicity",
author = "Shuanghu Yuan and Ellingrod, {Vicki L.} and Matthew Schipper and Stringer, {Kathleen A.} and Xuwei Cai and Hayman, {James A.} and Jinming Yu and Lawrence, {Theodore S.} and Kong, {Feng Ming}",
year = "2013",
month = "2",
doi = "10.1097/JTO.0b013e318274592e",
language = "English (US)",
volume = "8",
pages = "208--213",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "2",

}

TY - JOUR

T1 - Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer

AU - Yuan, Shuanghu

AU - Ellingrod, Vicki L.

AU - Schipper, Matthew

AU - Stringer, Kathleen A.

AU - Cai, Xuwei

AU - Hayman, James A.

AU - Yu, Jinming

AU - Lawrence, Theodore S.

AU - Kong, Feng Ming

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

KW - Non-small-cell lung cancer

KW - Radiotherapy

KW - Single nucleotide polymorphism

KW - Toxicity

UR - http://www.scopus.com/inward/record.url?scp=84873850738&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873850738&partnerID=8YFLogxK

U2 - 10.1097/JTO.0b013e318274592e

DO - 10.1097/JTO.0b013e318274592e

M3 - Article

C2 - 23334061

AN - SCOPUS:84873850738

VL - 8

SP - 208

EP - 213

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 2

ER -