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

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)19174-19187
頁數14
期刊Cancer Medicine
12
發行號18
DOIs
出版狀態已發佈 - 9月 2023

ASJC Scopus subject areas

  • 腫瘤科
  • 放射學、核子醫學和影像學
  • 癌症研究

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