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Association Of Single Nucleotide Polymorphisms With Radiation Induced Lung Injury And Survival In Radiotherapy Among Lung Cancer Patients

Posted on:2017-12-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q WangFull Text:PDF
GTID:1364330512454427Subject:Clinical medicine
Abstract/Summary:
Part I:Association of single nucleotide polymorphisms with radiation pneumonitis among lung cancer patients receiving radiotherapyAim:To investigate the relation between single nucleotide polymorphisms of DNA repair and inflammation factors and radiation pneumonitis among lung cancer patients.Materials and methods:From 2012 to 2015, we included 141 lung cancer patients who received thoracic radiotherapy and detected genetic polymorphisms of DNA repair genes and inflammation factors by PCR-LDR method. The primary endpoint was ≥3 radiation pneumonitis evaluated by NCI CTCAE 4.0 criteria.Results:A total of 141 patients of lung cancer were enrolled from 2012 to 2015. Among the enrolled patients, most were males (63.1%).11 patients were diagnosed as small cell lung cancer, the others were adenocarcinoma (37.6%) and squamous cell cancer (50.4%). With the median follow-up time of 19.66 months,71.6% lung cancer patients experienced disease progression or death,17.7% patients experienced ≥3 radiation pneumonitis. After adjusting for ECOG performance status, gender, age, clinical stage, histological type, smoking status, treatment and dosimetric factors, the Cox regression analyses revealed ATM rs664677, AIM2 rs2298803, rs855871, TGFβ1 rs1800469, rs1982073 were related to radiation pneumonitis susceptibility among lung cancer patients. ATM rs664677 T allele, AIM2 rs2298803 C allele, rs855871 G allele, TGFβ1 rs1800469 C allele, rs1982073 T allele were the risk alleles in prediction of radiation pneumonitis. Further analyses revealed TGFβ1 rs 1800469 C+rs1982073 T and AIM2 rs2298803 C+rs855871 G were the risk haplotypes of radiation pneumonitis.Conclusions:Genetic polymorphisms of TGFβ1 and AIM2 might be the predictive factors of radiation pneumonitis among lung cancer patients who received radiotherapy.Part Ⅱ:Association of single nucleotide polymorphisms with survival benefit among lung cancer patients receiving radiotherapyAim:To investigate the relation between single nucleotide polymorphisms of DNA repair and inflammation factors and survival benefit among lung cancer patients.Materials and methods:From 2012 to 2015, we enrolled 141 inoperable lung cancer patients receiving radiotherapy. We detected genetic polymorphisms of DNA repair genes and inflammation factors by PCR-LDR method. The primary endpoint was survival benefit.Results:A total of 141 inoperable lung cancer patients were included from 2012 to 2015. With the median follow-up time of 19.66 months,71.6% lung cancer patients experienced disease progression or death. After adjusting for ECOG performance status, gender, age, clinical stage, histological type, smoking status, treatment and dosimetric factors, the Cox regression analyses revealed TP53 rs 1042522, AIM2 rs2298803, rs855871, IL-18 rs4937113 were related to survival among lung cancer patients. TP53 rs1042522 C allele, AIM2 rs2298803 C allele, rs855871 G allele, IL-18 rs4937113 A allele were the risk alleles in prediction of poor prognosis.Conclusions:Genetic polymorphisms of TP53, AIM2 and IL-18 might be the predictive factors of survival among lung cancer patients.
Keywords/Search Tags:lung cancer, radiation, radiation pneumonitis, genetic polymorphism, survival
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