The association of plasma TGFβ1 during radiotherapy and genotypes of TGFβ1 pathway in patients with non-small cell lung cancer.

Abstract

e21115 Background: Radiation induced thoracic toxicities (RITT) in lung, esophagus and pericardium are dose-limited toxicities in patients with non-small cell lung cancer (NSCLC). Plasma transforming growth factor-beta1 (TGFβ1) and its change during radiotherapy was reported as a biomarker and single nucleotide polymorphisms (SNP) in TGFβ1 pathway was associated with RITT in our previous studies. In order to explore the mechanism of RITT, we tested whether plasma TGFβ1 was associated with genotypes of TGFβ1, tissue plasminogen activator (tPA) and angiotensin converting enzyme (ACE). Methods: Patients with stage I-III NSCLC enrolled in prospective clinical trials were eligible. All patients received radiotherapy with or without concurrent chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4–5 weeks (40–50 Gy) during RT. Plasma TGF-β1 was measured using an enzyme-linked immunosorbent assay. The DNA samples extracted from blood before treatment were analyzed for the following genetic variations: TGFβ1 509C/T, TPA -7351 C/T, and ACE I/D. Results: 76 NSCLC patients received definitive radiotherapy (median dose 66 Gy) were enrolled. For the entire group of patients, the mean pre-RT TGFß1 level was 10.7±2.3 ng/ml, and the mean during-RT TGFß1 level was 6.0±0.7 ng/ml. No significant TGFß1 level differences were found at pre-RT and during-RT in patients with different genotypes of TGFß1 and tPA. Only ACE DD group had marginally higher pre-RT TGFß1 level than II and ID group (DD 23.6ng/ml vs. II 9.0ng/ml vs. ID 7.5ng/ml, p = 0.05), but no difference at during-RT(p=0.346) or during-RT/pre-RT ratio(p = 0.433). However, patients with TGFß1 509CC had higher elevation of plasma TGF ß1 level at fourth week during-RT than T allele carriers (TGFß1 level ratio of during-RT/pre-RT were CC 1.4±0.2 vs. T allele carriers 0.7±0.1, p=0.047). Conclusions: This exploratory study demonstrated that patients with TGFß1 509CC had higher elevation of plasma TGF ß1 level at fourth week during-RT than T allele carriers. This can help explain the correlation of TGF ß1 level elevation and higher risk of radiation induced lung toxicity in patients with NSCLC.