title: TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy.
abstract: Transforming growth factor (TGF) -β1 signaling is involved in cancer-cell metastasis. We investigated whether single nucleotide polymorphisms (SNPs) at TGFβ1 were associated with overall survival (OS) and distant metastasis-free survival (DMFS) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy, with or without chemotherapy.
  
  
  
  We genotyped TGFβ1 SNPs at rs1800469 (C-509T), rs1800471 (G915C), and rs1982073 (T+29C) by polymerase chain reaction-restriction fragment length polymorphism in blood samples from 205 NSCLC patients who had had definitive radiotherapy at one institution in November 1998-January 2005. We also tested whether the TGF-β1 rs1982073 (T+29C) SNP affected the migration and invasion of A549 and PC9 lung cancer cells.
  
  
  
  Median follow-up time for all patients was 17 months (range, 1-97 months; 39 months for patients alive at the time of analysis). Multivariate analysis showed that the TGFβ1 rs1800469 CT/CC genotype was associated with poor OS (hazard ratio [HR] = 1.463 [95% confidence interval {CI} = 1.012-2.114], P = 0.043) and shorter DMFS (HR = 1.601 [95% CI = 1.042-2.459], P = 0.032) and that the TGFβ1 rs1982073 CT/CC genotype predicted poor DMFS (HR = 1.589 [95% CI = 1.009-2.502], P = 0.046) and poor brain MFS (HR = 2.567 [95% CI = 1.155-5.702], P = 0.021) after adjustment for age, sex, race, performance status, smoking status, tumor histology and volume, stage, receipt of concurrent radiochemotherapy, number of chemotherapy cycles, and radiation dose. Transfection with TGFβ1+29C (vs. +29T) stimulated the migration and invasion of A549 and PC9 cells, suggesting that TGFβ1+29C may be linked with increased metastatic potential.
  
  
  
  TGFβ1 genotypes at rs1800469 and rs1982073 could be useful for predicting DMFS among patients with NSCLC treated with definitive radiation therapy. These findings require validation in larger prospective trials and thorough mechanistic studies.
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
mesh_terms: D000072283:A549 Cells; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1