Abstract
Matrix metalloproteinase-1 (MMP-1) has been implicated in several inflammatory and fibrotic diseases. We hypothesized that genetic variations in the MMP1 promoter region are associated with risk of radiation-induced lung injury (RILI). A cohort of 251 lung cancer patients was genotyped for five single nucleotide polymorphisms in the MMP1 promoter region. We found that rs1144393 AG/GG was strongly correlated with an increased occurrence of grade ≥ 2 RILI (p = 0.002). Additionally, patients with the rs1144393 AG/GG genotypes exhibited higher MMP-1 expression than patients with the AA genotype in lung tissues (n = 28, p = 0.022) and plasma samples (n = 40, p = 0.018). Our results indicated that rs1144393 in the MMP1 promoter region can be a predictor of grade ≥ 2 RILI in lung cancer patients treated with thoracic radiation.
Highlights
Radiotherapy is an important therapeutic modality for lung cancer [1]; radiation-induced lung injury (RILI) diminishes the efficacy of radiotherapy [2]
Our results indicated that rs1144393 in the MMP1 promoter region can be a predictor of grade ≥ 2 RILI in lung cancer patients treated with thoracic radiation
Researches demonstrated that dosimetric parameters, including mean lung dose (MLD) and percent lung volume receiving more than a threshold radiation dose (VDose), might provide a guide to assess the risk of RILI in the treatment- planning process [8,9,10]
Summary
Radiotherapy is an important therapeutic modality for lung cancer [1]; radiation-induced lung injury (RILI) diminishes the efficacy of radiotherapy [2]. Previous studies investigated and identified multiple therapeutic and patient-related factors, such as Karnofsky performance status (KPS), chronic lung disease, smoking status, and chemotherapy, that may influence RILI risk [4,5,6,7]. Studies have suggested that increased levels of circulating MMP-1 may serve as a molecular biomarker for IPF [16] These facts suggested that MMP-1 may be involved in the RILI process. Other SNPs [−519 A > G (rs1144393), −422A > T (rs475007), −340 A > G (rs514921), and −320T > C (rs494379)] in the MMP1 promoter region exhibited haplotype effects on MMP1 activity [19]. We investigated the association of these five SNPs with the occurrence of RILI in lung cancer patients treated with radiotherapy
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