Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date

BACKGROUND: Oral cancers are preceded by oral potentially malignant disorders (OPMD). Understanding genetic susceptibility for OPMD risk could provide an opportunity for risk assessment of oral cancer through early disease course. We conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk. METHODS: We identified all relevant studies examining associations of SNPs with OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted world-wide between January, 2000 and February, 2016 using a combined keyword search on PubMed. Of these, 47 studies that presented results as odds ratios and 95% CI were considered for full review. RESULTS: The majority of eligible studies that explored candidate gene associations for OPMD were small (N < 200 cases), limiting their scope to provide strong inference for any SNP identified to date in any population. Commonly studied SNPs were genes of carcinogen metabolism (n = 18 studies), DNA repair (n = 11 studies), cell cycle control (n = 8 studies), extra-cellular matrix alteration (n = 8 studies) and immune-inflammatory (n = 6 studies) pathways. Based on significant associations as reported by two or more studies, suggestive markers included SNPs in GSTM1 (null), CCND1 (G870A), MMP3 (-1171; promotor region), TNFα (-308; rs800629), XPD (codon 751) and Gemin3 (rs197412) as well as in p53 (codon 72) in Indian populations. However, an equal or greater number of studies reported null or mixed associations for SNPs in GSTM1 (null), p53 (codon 72), XPD (codon 751), XRCC (rs25487 C/T), GSTT1 (null) and CYP1A1m1 (MspI site). CONCLUSION: Candidate gene association studies have not yielded consistent data on risk loci for OPMD. High-throughput genotyping approaches for OPMD, with concurrent efforts for oral cancer, could prove useful in identifying robust risk-loci to help understand early disease course susceptibility for oral cancer.