title: 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 GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found inNOTCH1, BRCA1, COL9A1, andHSPA13genes 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.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chung
authors.affiliation: Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Oral Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ka-Wo
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Cheng-Che E
authors.initials: CE
authors.lastname: Lan
authors.affiliation: Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.affiliation: Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. ycko@mail.cmu.edu.tw.|Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D016022:Case-Control Studies; D024081:Collagen Type IX / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008409:Mastication; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D031721:Piper betle / Q000009:adverse effects*; D010936:Plant Extracts / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D051881:Receptor, Notch1 / Q000235:genetics; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; C439970:COL9A1 protein, human; D024081:Collagen Type IX; D018840:HSP70 Heat-Shock Proteins; C086345:HSPA13 protein, human; C497761:NOTCH1 protein, human; D010936:Plant Extracts; D051881:Receptor, Notch1