Single Nucleotide Polymorphisms Of The TGFβ1Gene And Its Correlation To Radiation Pneumonitis In Lung Cancer Patients Biological

Objective:The aim of this study was to correlate Single Nucleotide Polymorphisms(SNP) of the Transforming growth factor-β (TGF β1) Gene in lung cancer patients during radiation therapy (RT) with the occurrence of radiation pneumonitis(RP).Methods:Using136available genomic DNA samples from lung cancer patients who received three-dimensional conformal radiation therapy,we genotyped four SNPs of the TGF β1gene (rs1800468: A-800G, rs1800469:C-509T,rs1800470:T869C,rs1800471: G915C) by SNaPshot SNP method.37blood samples before, in the middle of, at the end of RT and2and4weeks after RT were analyzed for TGFβ1by performing enzyme-linked immunosorbent assay. The predictive values of dosimetric factors for RP were evaluated, too.Results:Univariate analysis found TC/CC genotypes of TGF β1rs1800470:T869C to be associated with a statistically significantly lower risk of RP (HR=0.389;95%CI,0.176-0.860; P=0.018), compared with the TT genotype.However, during the period of radiation treatment, the TGF-β1level of TC genotype is significantly lower than TT/CC genotype. The mean pretreatment TGF-β1level did not differ between RP and non-RP groups. However, during the period of radiation treatment, the TGF-β1level began to increase at the end of RT in the RP group and became significantly higher4weeks after RT (p=0.005). Using an ANOVA model for repeated-measures,we found significant associations between the changes of TGFβ1during the time course of the RT and the risk of developing RP (p<0.001). Most of the dosimetric factors showed a significant association with RP.Conclusions:Our results show that the TC/CC genotypes of TGF β1rs10800470:T869C could be correlated with RP and the incorporation of the biological parameters into the dosimetric data could be useful for predicting symptomatic RP.