Abstract
A number of genetic variants were suggested to be associated with oral malignancy, few variants can be replicated. The aim of this study was to identify significant variants that enhanced personal risk prediction for oral malignancy. A total of 360 patients diagnosed with oral squamous cell carcinoma, 486 controls and 17 newly diagnosed patients with OPMD including leukoplakia or oral submucous fibrosis were recruited. Fifteen tagSNPs which were derived from somatic mutations were genotyped and examined in associations with the occurrence of oral malignancy. Environmental variables along with the SNPs data were used to developed risk predictive models for oral malignancy occurrence. The stepwise model analysis was conducted to fit the best model in an economically efficient way. Two tagSNPs, rs28647489 in FAT1 gene and rs550675 in COL9A1 gene, were significantly associated with the risk of oral malignancy. The sensitivity and specificity were 85.7% and 85.5%, respectively (area under the receiver operating characteristic curve (AUC) was 0.91) for predicting oral squamous cell carcinoma occurrence with the combined genetic variants, betel-quid, alcohol and age. The AUC for OPMD was only 0.69. The predictive probability of squamous cell carcinoma occurrence for genetic risk score without substance use increased from 10% up to 43%; with substance use increased from 73% up to 92%. Genetic variants with or without substance use may enhance risk prediction for oral malignancy occurrence in male population. The prediction model may be useful as a clinical index for oral malignancy occurrence and its risk assessments.
Highlights
Oral squamous cell carcinoma (OSCC) is a growing public health problem in the world[1]
A number of genetic variants were suggested to be associated with OSCC occurrence by association studies [23, 24] and genome-wide association studies [25], few variants are able to be consistent in association with OSCC among the different population
Attention has turned to the somatic mutations identified by next-generation sequencing approaches which are reported in the Cancer Genome Atlas that has shown promising genes associated with the initiation and progression of OSCC [25, 27,28,29]
Summary
Oral squamous cell carcinoma (OSCC) is a growing public health problem in the world[1]. Various anatomical sites of oral cavity showed different incidence rates of OSCC and their. The survival rate increased with early detection which suggests the importance of the early prevention for OSCC in reducing morbidity and mortality [4]. With increased understanding of genetics and environmental risk factors in oral tumorigenesis, novel approaches have developed for prevention, early detection, risk stratification and treatment of OSCC. Major risk factors associated with the occurrence of oral malignancy are genetic risk factors [5, 6] and environmental risk factors, including betel quid (BQ) chewing and cigarette and alcohol consumption [7, 8]. Genetic and environmental risk factors have interactive effects on the occurrence of oral malignancy [9]
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