Association between DNA Repair Gene Pathway Polymorphisms and Risk of Radiation Pneumonitis: A Systematic Review and Meta-Analysis

Abstract

<h3>Purpose/Objective(s)</h3> Radiation pneumonitis is a dose-limiting toxicity of radiotherapy. Genetic variation in this pathway affects post-radiotherapy DNA repair and subsequently the level of toxicity. Previous studies published within this area in lung cancer treatment have been inconsistent. Our meta-analysis therefore aimed at examining the effect of SNPs on radiation pneumonitis of lung cancer patients receiving radiotherapy. <h3>Materials/Methods</h3> We performed a systematic review of relevant studies published on or before 12 October 2021 on PubMed, Scopus, Embase, and Web of Science databases. Studies with genotyping data of lung cancer patients receiving radiotherapy were included. Conference abstracts, reviews, non-English articles, studies in which radiotherapy was used as a neoadjuvant therapy were excluded. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS) by two independent reviewers. We calculated the pooled odds ratios and the 95% confidence intervals to evaluate the association between each DNA repair gene pathway polymorphism and all-grade radiation pneumonitis. The allelic, dominant, recessive, homozygous and heterozygous genotype models were used to assess the association. <h3>Results</h3> 706 studies were initially obtained after database searching and de-duplication. 15 studies (2964 patients) were included in the systematic review. The median follow-up time ranged from 3 months to 39.5 months. Under the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing radiation pneumonitis compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04, I-square = 0%, total number of patients: 341). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing radiation pneumonitis compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001, I-square = 0%, total number of patients: 432). Other SNPs were found to have no significant associations with all-grade radiation pneumonitis. <h3>Conclusion</h3> This systematic review and meta-analysis showed that two SNPs in the DNA repair gene pathway are significantly associated with the risks of developing radiation pneumonitis in lung cancer patients. Further cohort studies assessing a combination of DNA repair gene polymorphisms with a greater sample size are needed.