Dataset Information
Functional polymorphisms of base excision repair genes XRCC1 and APEX1 predict risk of radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.
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ABSTRACT: Purpose
To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development.Methods and materials
We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non-small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes.Results
We found that SNPs of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade ≥2 RP (XRCC1: AA vs. GG, adjusted hazard ratio [HR] = 0.48, 95% confidence interval [CI], 0.24-0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64-7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001).Conclusions
SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings.
SUBMITTER: Yin M
PROVIDER: S-EPMC3136565 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Publications
Functional polymorphisms of base excision repair genes XRCC1 and APEX1 predict risk of radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.
International journal of radiation oncology, biology, physics 20110321 3
<h4>Purpose</h4>To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development.<h4>Methods and materials</h4>We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non-small cell lung cancer ( ...[more]