Single Nucleotide Polymorphism at rs1982073:T869C of the TGFβ1 Gene Is Associated With the Risk of Radiation Pneumonitis in Patients With Non–Small-Cell Lung Cancer Treated With Definitive Radiotherapy

Abstract

Our results showed that CT/CC genotypes of TGFbeta1 rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC treated with definitive radio(chemo)therapy and thus may serve as a reliable predictor of RP.

Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-β1-mediated tissue fibrosis

“…This idea is further supported by studies demonstrating that genetic polymorphisms play a role in an individual's tissue response to radiation (6,31). Interestingly, polymorphisms in the gene coding for TGF-␤1 have been directly implicated as modulators of tissue response to radiation (72). The use of genetically inbred animals for the study of lymphatic function obviates these differences and may simplify analysis.…”

Effects of lysophosphatidic acid and its receptors LPA__AMB__frac13; on radiation pneumonitis

“…The molecular mechanisms of RP remain unclear, but it is generally believed that the process is regulated by the release and activation of various proinflammatory and profibrotic cytokines by damaged and activated cells, including transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-· (TNF-·), and interleukin-1ß (IL-1ß). In this complex process, TGF-ß1 is one of the most extensively studied cytokines and plays a particularly important role in the development of RP (4). In the clinic, an elevated plasma TGF-ß1 level during RT is a predictive factor for RP (5).…”

“…It is well known that the effects of LPA are mediated by the binding to and activation of specific G protein-coupled receptors. There are 5 high-affinity cognate receptors that have been identified as receptors for LPA, termed LPA 1 , LPA 2 , LPA 3 , LPA 4 , and LPA 5 . These receptors have distinct tissue distributions and effector signal pathways (8).…”

Advances in targeting the transforming growth factor β1 signaling pathway in lung cancer radiotherapy (Review)

“…TGFB1 is considered a critical cytokine in the development of late normal tissue injury following lung cancer radiotherapy (37)(38)(39). Monitoring TGFB1 in the plasma and screening for TGFB1 polymorphisms may assist in identifying normal tissue injury risk in patients with lung cancer (38,52,55). Although the molecular mechanisms underlying the TGFB1 signaling pathway and the SMAD effector complex have been previously established (24,25), upstream regulators of the TGFB1 signaling pathway and the mechanisms by which they regulate the components of the pathway as the tumor develops require further study.…”