The X-ray repair cross-completing gene 1 (XRCC1) polymorphisms and lung cancer incidence – a confirmatory umbrella review of observational evidence

Abstract

Introduction and aim. Lung cancer (LC) is a leading cause of cancer-related deaths worldwide, with X-ray repair cross-comple menting gene 1 (XRCC1) playing a crucial role in DNA repair and influencing LC risk through genetic mutations. Despite nu merous meta-analyses, results have been inconsistent. This study systematically evaluated existing meta-analyses to clarify the association between XRCC1 gene variations and LC. Material and methods. A comprehensive literature search was conducted using Scopus, Web of Science, Embase, and Co chrane databases. The present Umbrella review followed PRISMA and MOOSE guidelines. The AMSTAR tool assessed the meth odological quality of the included studies. Analysis of the literature. A total of 28 data sets were analyzed: 9 for the rs25487 (codon 399), 11 for the rs1799782 (codon 194), and 8 for the rs25489 (codon 280) polymorphisms. Significant associations were found with odds ratios ranging from 0.93 to 1.92 (p<0.05) in 16 data sets. XRCC1 rs25487/codon 399 and rs1799782/codon 194 were strongly linked to LC risk, while rs25489 (codon 280) was not. Twelve datasets showed significant heterogeneity, and publication bias was not detected in 24 datasets. Most meta-analyses demonstrated high methodological quality. Conclusion. These findings suggest that XRCC1 (rs25487/codon 399 and rs1799782/codon 194) gene polymorphisms have the potential to serve as biomarkers for the early identification and management of LC risk.