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Article: Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer
Title | Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer |
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Authors | |
Keywords | Non-small-cell lung cancer Radiotherapy Single nucleotide polymorphism Toxicity |
Issue Date | 2013 |
Citation | Journal of Thoracic Oncology, 2013, v. 8, n. 2, p. 208-213 How to Cite? |
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. Copyright © 2012. |
Persistent Identifier | http://hdl.handle.net/10722/266956 |
ISSN | 2023 Impact Factor: 21.0 2023 SCImago Journal Rankings: 7.879 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yuan, Shuanghu | - |
dc.contributor.author | Ellingrod, Vicki L. | - |
dc.contributor.author | Schipper, Matthew | - |
dc.contributor.author | Stringer, Kathleen A. | - |
dc.contributor.author | Cai, Xuwei | - |
dc.contributor.author | Hayman, James A. | - |
dc.contributor.author | Yu, Jinming | - |
dc.contributor.author | Lawrence, Theodore S. | - |
dc.contributor.author | Kong, Feng Ming | - |
dc.date.accessioned | 2019-01-31T07:20:05Z | - |
dc.date.available | 2019-01-31T07:20:05Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Journal of Thoracic Oncology, 2013, v. 8, n. 2, p. 208-213 | - |
dc.identifier.issn | 1556-0864 | - |
dc.identifier.uri | http://hdl.handle.net/10722/266956 | - |
dc.description.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. Copyright © 2012. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Thoracic Oncology | - |
dc.subject | Non-small-cell lung cancer | - |
dc.subject | Radiotherapy | - |
dc.subject | Single nucleotide polymorphism | - |
dc.subject | Toxicity | - |
dc.title | Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1097/JTO.0b013e318274592e | - |
dc.identifier.scopus | eid_2-s2.0-84873850738 | - |
dc.identifier.volume | 8 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 208 | - |
dc.identifier.epage | 213 | - |
dc.identifier.eissn | 1556-1380 | - |
dc.identifier.isi | WOS:000316204900016 | - |
dc.identifier.issnl | 1556-0864 | - |