Abstract
The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates that functional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side effects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Relevant articles were retrieved from PubMed, ISI Web of Science and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses were performed using the Stata software. A total of twenty articles were included in the present analysis. In the overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type of cancer, region and time of appearance of side effects subsequently. No significant association between ATM Asp1853Asn 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 patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. The TP53 Arg72Pro C 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 environmental exposures are warranted.
Highlights
Radiotherapy is the medical use of ionizing radiation, generally as part of cancer treatment to control or kill malignant cells
For TP53 Arg72Pro, variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patients in the stratified analysis by region (OR=0.71, 95%confidence intervals (CIs): 0.54-0.93, p=0.012)
Inclusion and exclusion criteria The following inclusion criteria were analyzed in selecting studies for the current meta-analysis: (i) evaluate the association between ataxia telangiectasia mutated (ATM) Asp1853Asn or TP53 Arg72Pro polymorphisms and radiotherapy adverse effects; (ii) use case-control design, consider patients developed with severe radiotherapy toxicities as cases and minimal radiotherapy toxicities as controls; (iii) include full-text manuscrips only; (iv) describe useful allele and genotype frequencies for estimating an odds ratios and 95% confidence intervals (95%CIs)
Summary
Radiotherapy is the medical use of ionizing radiation, generally as part of cancer treatment to control or kill malignant cells. A number of epidemiological studies have been performed to investigate the associations between SNPs and risk of radiotherapy adverse effects such as subcutaneous fibrosis, telangiectasia and radiation-induced pneumonitis. We performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. No significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. No significant association between ATM Asp1853Asn 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 patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. Further studies that take into consideration treatment-related factors and patient lifestyle including environmental exposures are warranted
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