Combined Genetic Biomarkers and Betel Quid Chewing for Identifying High Risk Group for Oral Cancer Occurrence

Abstract We integrated genetic risk scores (GRS) and environmental factors for identifying high risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case - control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between genetic risk score and Betel quid (BQ) chewing. We employed receiver operating characteristic (ROC) curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1 and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores=4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ and cigarette: adjusted OR: 4.42 (95% CI: 1.34-14.55). The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR=70.77; 95% CI 8.70-575.73). The synergy index was 16.58(95% CI 2.27-70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence.

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