Single-nucleotide polymorphism at alcohol dehydrogenase 1B: A susceptible gene marker in oro-/hypopharyngeal cancers from genome-wide association study

Hui-Tzu Chien; Chia-Lung Tsai; Chi-Kuan Young; Yun-Shien Lee; Chun-Ta Liao; Chih-Ching Yeh; Angel Chao; Kai-Lun Cho; Ching-Han Chen; Shiang-Fu Huang

doi:10.1002/cam4.6506

Single-nucleotide polymorphism at alcohol dehydrogenase 1B: A susceptible gene marker in oro-/hypopharyngeal cancers from genome-wide association study

Cancer Med. 2023 Sep;12(18):19174-19187. doi: 10.1002/cam4.6506. Epub 2023 Sep 14.

Authors

Hui-Tzu Chien^{1

2}, Chia-Lung Tsai³, Chi-Kuan Young^{4

5}, Yun-Shien Lee^{1

6}, Chun-Ta Liao⁷, Chih-Ching Yeh^{8

9

10}, Angel Chao¹¹, Kai-Lun Cho⁷, Ching-Han Chen¹², Shiang-Fu Huang^{7

13}

Affiliations

¹ Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
² Geriatric and Long-Term Care Research Center, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
³ Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
⁴ Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan.
⁵ Medical College, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁶ Department of Biotechnology, Ming Chuan University, Taoyuan, Taiwan.
⁷ Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁸ Master Program in Applied Molecular Epidemiology, College of Public Health, Taipei Medical University, Taipei, Taiwan.
⁹ School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
¹⁰ Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
¹¹ Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
¹² School of Medicine, Chang Gung Medical College, Chang Gung University, Taoyuan, Taiwan.
¹³ Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.

Abstract

Introduction: In the era of precision preventive medicine, susceptible genetic markers for oro-/hypopharyngeal squamous cell carcinoma (OPSCC) have been investigated for genome-wide associations.

Materials and methods: A case-control study including 659 male head and neck squamous cell carcinoma (HNSCC) patients, including 331 oropharyngeal cancer, treated between March 1996 and December 2016 and 2400 normal controls was performed. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OPSCC.

Results: We analyzed the allele frequencies of 664,994 autosomal SNPs in 659 HNSCC cases; 7 SNPs scattered in loci of chromosomes 5, 7, 9, 11, and 19 were significant in genome-wide association analysis (Pc < 1.0669 × 10^-7 ). In OPSCCs (n = 331), two clustered regions in chromosomes 4 and 6 were significantly different from the controls. We successfully identified a missense alteration of the SNP region in alcohol dehydrogenase 1B (ADH1B) (https://genome.ucsc.edu; hg38); the top correlated locus was rs1229984 (p = 1 × 10^-11 ). Adjusted for environmental exposure, including smoking, alcohol, and areca quid, a region in chromosome 12, related to alcohol metabolism, was found to independently increase the susceptibility to OPSCC. The ADH1B rs1229984 AA genotype had better overall survival compared to the AG and GG genotypes (p = 0.042) in OPSCC. The GG genotype in rs1229984 was significantly associated with a younger age of onset than other genotypes (p = 0.001 and <0.001, respectively) in OPSCC patients who consumed alcohol.

Conclusion: ADH1B was an important genetic locus that significantly correlated with the development of OPSCCs and patient survival.

Keywords: alcohol dehydrogenase 1B; aldehyde dehydrogenase 2; genome-wide association study; head and neck cancer; oropharyngeal cancer.

Abstract

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