DNA Damage and Repair and Cancer Risk: A Systematic Review and Meta-Analysis of 55 Case- Control Studies

Abstract

DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair capacity compared with those with the highest capacity. We included 55 case-control studies that evaluated 12 different cancers using 10 different DNA repair assays. The pooled OR of cancer risk (all cancer types combined) was 2.92 (95% Confidence Interval (CI)= 2.49, 3.43) for the lowest DNA repair. Lower DNA repair was associated with all studied cancer types, and pooled ORs (95% CI) ranged from 2.02 (1.43, 2.85) for skin cancer to 7.60 (3.26, 17.72) for hepatocellular carcinoma. All assays, except the homologous recombination repair, showed statistically significant associations with cancers. The effect size ranged from 1.90 (1.00, 3.60) for ETOP-induced double strand break assay to 5.06 (3.67, 6.99) for γ-H2AX. The consistency and strength of the associations supports the use of these phenotypic biomarkers; however large-scale prospective studies will be important for understanding the use of this biomarker related to age and screening initiation.