| Objective:This study was to investigate the association between the single nucleotide polymorphisms(SNPs)with the susceptibility of radiation pneumonitis( RP) among lung cancer patients after radiotherapy in Southwest China, evaluating risk and predicting of RP before lung cancer patients treat with radiation therapy。Method:Lung cancer patients undergoing chest radiotherapy were recruited at the Department of Oncology at Daping Hospital in Chongqing and at the Cancer Center of Chengdu Military General Hospital in Chengdu. Each patient follow-up at least 3 months. RP events were graded with the Common Terminology Criteria for Adverse Events 3.0(CTCAE 3.0). Genome DNA of each patient extracted from peripheral anticoagulant blood. Total 40 SNPs were selected and genotyped with the improved multiple ligase detection reaction(i MLDR) by experts who were blinded to the patients’ informations. Cox proportional hazard models were performed to identify SNPs associated with risk of RP. The cumulative RP hazard by genotypes were evaluated using the Kaplan-Meier analysis. A P≤0.05 was considered statistically significant.Result: We finally recruited 305 qualified lung cancer patients,18.7%(57) experienced grade ≥ 2 RP,and 7.9%(24) experienced grade ≥ 3 RP. The 301 patients’ genome DNA samples were successful Genotyped. Among the clinical factors,we found age ≥ 65, PS ≥ 3, smoke,V8 > 45%, V10 > 30%,V15 > 25%, V20>18% and V30>10% were associated with the risk of grade ≥ 2 RP. As fto genetic factors, IL1 B rs1143623 G, TNFRSF1 B rs1061622 G, MIF rs755622 C mutated alleles and IL6 rs2069840 heterozygote CG carriers were associated with significantly increased risk of grade ≥2 RP. SNP interactions analysis found these genotypes such as rs1143623GC*rs1061622GT, rs1061622GT*rs755622GC, rs1143623GC* rs755622 GC, rs1143623GC*rs755622CC and rs1143623GG*rs2069840CC have interactions during the process of grade ≥2 RP. In addition, mutated allele TNFRSF1 B rs1061622 G, MIF rs755622 C, EGFR rs2075112 G, EGFR rs11977660 C and IL13 rs20541 mutated TT carrier were associated with significantly increased risk of grade ≥3 RP,while the EGFR rs11977660 T allele and the TNF rs1799724 CT genotype were associated with lower RP risk compared with other genotypes. Interactions analysis found genotypes such as rs1061622TT*rs2075112AG, rs1061622TT*rs755622 GC, rs11977660CT*rs755622CC, rs20541TT*rs 2075112 AG, rs20541CT* rs755622 CC, rs2075112AG*rs755622GC, rs2075112AG*rs755622CC and rs2075112 GG *rs755622CC have interactions during the process of grade ≥3 RP.Conclusion:1.The clinical factors such as age, PS, smoke, V8, V10, V15, V20 and V30 were significantly associated with the susceptibility to grade ≥3 RP among the lung cancer patients with radiotherapy.2.Univariate analysis found IL1 B rs1143623 G/C, TNFRSF1 B rs1061622 G/T, MIF rs755622 G/C and IL6 rs2069840C/G variations were associated with grade ≥2 RP risk among lung cancer patients after radiotherapy in Southwest China. After adjusted by the age, PS, somke and V20, the IL1 B rs1143623 G/C and MIF rs755622 G/C were still associated with grade ≥2 RP RP risk. Both the existence of these genotypes rs1143623GC*rs1061622GT, rs1061622 GT*rs 755622 GC, rs1143623 GC*rs755622 GC, rs1143623 GC*rs755622 CC and rs1143623 GG*rs2069840 CC have an interaction functions in the development of grade ≥2 RP.3.Univariate analysis found IL13 rs20541 C/T, TNFRSF1 B rs1061622 G/T, MIF 755622 G/C and TNF rs1799724 C/T variations were associated with grade ≥3 RP risk among lung cancer patients after radiotherapy in Southwest China. Multivariate analysis found MIF rs755622 G/C, EGFR rs2075112 A/G and EGFR rs11977660 C/T variations were associated with grade ≥3 RP RP risk. Both the existence of these genotypes rs1061622 TT*rs2075112 AG, rs1061622 TT*rs755622 GC, rs11977660 CT*rs755622 CC, rs20541 TT*rs 2075112 AG, rs20541 CT*rs755622 CC, rs2075112 AG*rs755622 GC 、 rs2075112 AG*rs755622 CC and rs2075112 GG *rs755622 CC have an interaction in the development of grade ≥3 RP risk. |
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