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 GRS and betel quid (BQ) chewing. We employed 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% confidence interval (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. Cancer Prev Res; 10(6); 355-62. ©2017 AACR.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the world
Subjects A total of 447 patients diagnosed with OSCC were recruited from the Department of Dentistry and the Department of Otorhinolaryngology, Kaohsiung Medical University Hospital (KMUH; Kaohsiung, Taiwan) in the southern Taiwan (n 1⁄4 285) and Changhua Christian Hospital (CCH; Changhua, Taiwan) in mid-Taiwan (n 1⁄4 162)
Selection of tag SNPs of susceptibility candidate genes We evaluated and chose susceptibility genes, which have been reported in association between betel quid (BQ) use and development of OSCC
Summary
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the world. The most common type of oral cancer is OSCC, which accounts for approximately 90% of all malignant oral neoplasms [1]. The previous studies conducted a survey (from 1975 to 1996) of 378 cancer patients in Taiwan, indicating that the 5-year survival rate for stage III oral cancer was 49%, declining to 30% for stage IV [2]. The survival rate for the earliest stage is >75%, which suggests the importance of the early detection for OSCC in reducing morbidity and mortality [3]. Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).
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