|Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer.|
|PMID: 23334061 Owner: NLM Status: MEDLINE|
|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.
|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|
|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't|
|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|
|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|
|Languages: eng Pagination: 208-13 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
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
Lung Neoplasms / complications, genetics*, therapy
Peptidyl-Dipeptidase A / blood, genetics*
Radiation Injuries / blood, etiology*
Thoracic Diseases / blood, etiology
Tissue Plasminogen Activator / blood, genetics*
Transforming Growth Factor beta1 / blood, genetics*
|R01 CA 142840-03/CA/NCI NIH HHS; R01 CA142840/CA/NCI NIH HHS; R21CA127057/CA/NCI NIH HHS; UL1RR024986/RR/NCRR NIH HHS|
|0/Transforming Growth Factor beta1; EC 184.108.40.206/Peptidyl-Dipeptidase A; EC 220.127.116.11/Tissue Plasminogen Activator|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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