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

Journal Article · Tue Nov 01 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

OSTI ID:21590433

Ming, Yin ^[1]; Zhongxing, Liao ^[2]; Zhensheng, Liu; Wang, Li-E ^[1]; Gomez, Daniel; Komaki, Ritsuko ^[2]; Qingyi, Wei ^[1]

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1. Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX (United States)
2. Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX (United States)

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.

• OSTI ID: 21590433
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 81; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BIOLOGICAL MARKERS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
DISEASES
DNA REPAIR
DOSES
EXCISION REPAIR
GENES
GENOTYPE
HAZARDS
LUNGS
MEDICINE
NEOPLASMS
NUCLEAR MEDICINE
ORGANS
PNEUMONITIS
RADIATION DOSES
RADIOLOGY
RADIOTHERAPY
REPAIR
RESPIRATORY SYSTEM
THERAPY