Single Nucleotide Polymorphisms as Markers of Genetic Susceptibility for Oral Submucous Fibrosis Risk: A Systematic Review and Meta-Analysis.

Background: Varied susceptibility to Oral submucous fibrosis (OSF) among individuals exposed to the same environmental variables indicates that genetic variation may contribute as a risk factor in its development. The objective was to comprehensively analyze the association between single gene polymorphisms (SNPs) and the risk of OSF.

Methods: This comprehensive systematic review encompassed all relevant published studies up until June 2024 that examined the influence of gene polymorphisms on the likelihood of OSF. The search was conducted across multiple databases, including Medline, Scopus, and EBSCOhost. Data were pooled in a random-effect meta-analysis where at least two studies on the same SNP tested the same genotyping model. The assessment of heterogeneity was conducted using the I² statistic. The Q-Genie tool was used to evaluate the quality of the included studies.

Results: Out of the 4573 papers initially searched, only 37 articles met the criteria to be included in this review. A total of 63 SNPs from 27 genes were tested, and 38 SNPs had significant associations. The meta-analysis revealed that five SNPs, including GSTM1 null (OR = 1.90; 1.41-2.56), GSTT1 null (OR = 2.41; 1.64-3.53), MMP3 (-1171; promoter region) (OR = 3.33; 1.45-7.61), XXCR3 (T vs. C) (OR = 1.70 (1.23-2.36)) and CYP1A1 m2 at Ncol site (-) (OR = 4.32; 1.22-15.29), are associated with an increased risk of OSF.

Conclusion: The limited SNPs identified in this review could be used as markers to identify patients at a higher risk of OSF. Further studies are warranted to validate the SNPs, which demonstrate contradictory results among the currently available studies.