Document Detail


Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer.
MedLine Citation:
PMID:  23334061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shuanghu Tiger Yuan; Vicki L Ellingrod; Matthew Schipper; Kathleen A Stringer; Xuwei Cai; James A Hayman; Jinming Yu; Theodore S Lawrence; Feng-Ming Spring Kong
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  8     ISSN:  1556-1380     ISO Abbreviation:  J Thorac Oncol     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-07-18     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  208-13     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / complications,  genetics,  therapy
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carcinoma, Non-Small-Cell Lung / complications,  genetics,  therapy
Carcinoma, Squamous Cell / complications,  genetics,  therapy
Chemoradiotherapy / adverse effects*
Enzyme-Linked Immunosorbent Assay
Esophagitis / blood,  etiology
Female
Follow-Up Studies
Humans
Lung Neoplasms / complications,  genetics*,  therapy
Male
Middle Aged
Neoplasm Grading
Peptidyl-Dipeptidase A / blood,  genetics*
Prognosis
Radiation Injuries / blood,  etiology*
Survival Rate
Thoracic Diseases / blood,  etiology
Tissue Plasminogen Activator / blood,  genetics*
Transforming Growth Factor beta1 / blood,  genetics*
Grant Support
ID/Acronym/Agency:
R01 CA 142840-03/CA/NCI NIH HHS; R01 CA142840/CA/NCI NIH HHS; R21CA127057/CA/NCI NIH HHS; UL1RR024986/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Transforming Growth Factor beta1; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.21.68/Tissue Plasminogen Activator
Comments/Corrections

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