title: Genetic variations in TGFβ1, tPA, and ACE and radiation-induced thoracic toxicities in patients with non-small-cell lung cancer.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, P.R. China.
authors: Shuanghu Tiger
authors: ST
authors: Yuan
authors: Vicki L
authors: VL
authors: Ellingrod
authors: Matthew
authors: M
authors: Schipper
authors: Kathleen A
authors: KA
authors: Stringer
authors: Xuwei
authors: X
authors: Cai
authors: James A
authors: JA
authors: Hayman
authors: Jinming
authors: J
authors: Yu
authors: Theodore S
authors: TS
authors: Lawrence
authors: Feng-Ming Spring
authors: FM
authors: Kong
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000235:genetics / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004941:Esophagitis / Q000097:blood / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011379:Prognosis; D011832:Radiation Injuries / Q000097:blood / Q000209:etiology*; D015996:Survival Rate; D013896:Thoracic Diseases / Q000097:blood / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1; D007703:Peptidyl-Dipeptidase A; D010959:Tissue Plasminogen Activator