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Association of single nucleotide polymorphisms with radiation-induced esophagitis

Objective To evaluate the relationship between single nucleotide polymorphism(SNP) of candidate genes and radiation-induced esophagitis (RIE) in patients with lung cancer. Methods Between Jan. 2004 and Aug. 2006,170 patients with pathologically diagnosed lung cancer were enrolled in this study. The total target dose was 45-70 Gy( median 60 Gy). One hundred and thirty-two patients were treated with three-dimensional conformal radiotherapy(3DCRT) and 38 with two-dimensional radiotherapy(2DRT).Forty-one patients received radiotherapy alone, 78 received sequential chemoradiotherapy and 51 received concurrent chemoradiotherapy. Thirty-seven SNPs in 20 DNA repair genes were analyzed by using PCR-based restrieted fragment length polymorphism(RFLP). These genes were apoptosis and inflammatory cytoking genes including ATM, ERCC1, XRCC3, XRCC1, XPD, XPC, XPG, NBS1, STK15, ZNF350, ADPRT,TP53, FAS, FASL, CYP2D6 * 4, CASPASE8, COX2,TGF-β, CD14 and ACE. The endpoint was grade ≥2 R I E. Results Forty of the 170 patients developed grade ≥2 R I E, including 36 in grade 2 and 4 in grade 3. Univariate analysis revealed that radiation technique and concurrent chemoradiotherapy were statistically significant relatives to the incidence of R I E (P = 0. 032,0.049) , and both of them had the trend associating with the esophagitis( P = 0.072,0. 094 ). An increased incidence of esophagitis was observed associating with the TGF-β1-509T and XPD 751 Lys/Lys genotypes ( χ2 = 5.65, P = 0.017 ;χ2 = 3.84, P = 0. 048 )in multivariate analysis. Conclusions Genetic polymorphisms in TGF-β1 gene and XPD gene have a significant association with radiation-induced esophagitis. 
 
Key words: 
Lung neoplasms/radiotherapy; Radiation-induced esophagitis;  Single nucleotide polymorphisms