Meta-analysis of Associations between ATM Asp1853Asn and TP53 Arg72Pro Polymorphisms and Adverse Effects of Cancer Radiotherapy

Background: The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairingradiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates thatfunctional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced sideeffects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asnand TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Materials and
Methods: Relevant articles were retrieved from PubMed, ISI Web of Science and the China National KnowledgeInfrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusioncriteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association betweenATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses wereperformed using the Stata software.
Results: A total of twenty articles were included in the present analysis. Inthe overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphismsand the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type ofcancer, region and time of appearance of side effects subsequently. No significant association between ATMAsp1853Asn and risk of radiotherapy adverse effects was found in any subgroup analysis. For TP53 Arg72Pro,variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patientsin the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found inthe subgroup analysis of tumor type and time of appearance of side effects.
Conclusions: The TP53 Arg72ProC allele might be a protective factor of radiotherapy-induced adverse effects among cancer patients from Asia.Further studies that take into consideration treatment-related factors and patient lifestyle including environmentalexposures are warranted.