title: Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development.
abstract: A number of genetic variants have been associated with cancer occurrence, however it may be the acquired somatic mutations (SMs) that drive cancer development. This study investigates the potential SMs and related genetic variants associated with the occurrence and development of head and neck squamous cell carcinoma (HNSCC). We identified several SMs in NOTCH1 from whole-exome sequencing and validated them in a 13-year cohort of 128 HNSCC patients using a high-resolution melting analysis and resequencing. Patients who have NOTCH1 SMs show higher 5-year relapse-free recurrence (P = 0.0013) and lower survival proportion (P = 0.0447) when the risk-associated SMs were analysed by Cox proportional hazard models. Interestingly, the NOTCH1 gene rs139994842 that shares linkage with SMs is associated with HNSCC risk (OR = 3.46), increasing when SMs in NOTCH1 are involved (OR = 7.74), and furthermore when there are SMs in conjunction to betel quid chewing (OR = 32.11), which is a related independent environmental risk factor after adjusting for substances use (alcohol, betel quid, cigarettes) and age. The findings indicate that betel quid chewing is highly associated with NOTCH1 SMs (especially with changes in EGF-like domains), and that rs139994842 may potentially serve as an early predictive and prognostic biomarker for the occurrence and development of HNSCC.
authors.affiliation: Department of Biomedical Sciences, College of Medicine Sciences and Technology, Chung Shan Medical University, Taichung, Taiwan.|Division of Allergy, Department of Pediatrics, Chung-Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan.|Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Shang-Lun
authors.initials: SL
authors.lastname: Chiang
authors.affiliation: Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.affiliation: Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chung
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig D-04103, Germany.
authors.forename: Albert Min-Shan
authors.initials: AM
authors.lastname: Ko
authors.affiliation: Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan.
authors.forename: You-Zhe
authors.initials: YZ
authors.lastname: Lin
authors.affiliation: Department of Public Health, College of Health Science, Kaohsiung Medical University, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ka-Wo
authors.initials: KW
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 Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Hua
authors.affiliation: Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Department of Dentistry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yuan-Chien
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Environment-Omics-Diseases Research Centre, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D018572:Disease-Free Survival; D004777:Environment; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008040:Genetic Linkage; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D000072417:Protein Domains; D051881:Receptor, Notch1 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1