Polymorphisms and environmental factors associated with orofacial clefts as potential markers for oral cancer risk.

Abstract

The etiological intersection between orofacial clefts and oral cancer may involve environmental factors modulating gene expression in shared biological pathways. This study aimed to investigate the association between orofacial clefts and oral potentially malignant disorders or oral squamous cell carcinoma, focusing on genetic variants and environmental risk factors. A case-control design was employed, comprising 48 histologically confirmed cases of oral potentially malignant disorders or oral squamous cell carcinoma and 96 age- and sex-matched controls. Information on family history of orofacial cleft, and biological and environmental risk factors, was collected through interviews. Genomic DNA was extracted from saliva samples and genotyped for rs1533767 (WNT11), rs9879992 (GSK3B), and rs3923087 and rs11867417 (AXIN2). Unadjusted and adjusted odds ratios (OR) for the associations between family history of orofacial cleft and oral potentially malignant disorders/oral cancer, and between environmental risk factors and oral potentially malignant disorders/oral cancer were calculated using STATA software. Genotype and allele frequency comparisons between groups were conducted using PLINK Software. Statistical significance was defined as p<0.05 and 95% confidence interval (95%CI). No statistically significant association was found between family history and orofacial clefts (p = 0.52). However, place of residence (adjusted OR:5.46, p < 0.001, 95%CI: 3.76-63.543), and three genetic variants-rs1533767 (OR: 1.94, p = 0.042, 95%CI: 1.018-3.694), rs3923087 (OR: 0.58, p = 0.038, 95%CI: 0.344-0.974), rs11867417 (OR: 0.51, p = 0.010, 95%CI: 0.304-0.857)-were associated with oral potentially malignant disorders and oral squamous cell carcinoma. These findings suggest that specific environmental risk factors and genetic variants may be associated with increased susceptibility to oral potentially malignant disorders and oral cancer.