Impact of alcohol dehydrogenase-aldehyde dehydrogenase polymorphism on clinical outcome in patients with hypopharyngeal cancer

Head Neck. 2018 Apr;40(4):770-777. doi: 10.1002/hed.25050. Epub 2017 Dec 29.

Abstract

Background: The purpose of this research was to investigate the association between alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms and hypopharyngeal squamous cell carcinoma (SCC) survival.

Methods: We genotyped ADH1B (rs1229984) and ALDH2 (rs671) single nucleotide polymorphisms (SNPs) in 85 Japanese male patients with hypopharyngeal SCC. The independent prognostic values of ADH1B-ALDH2 genotypes were analyzed by univariate and multivariate proportional hazard Cox regression, taking well-known clinical risk factors into account.

Results: Heavy drinkers with ALDH2*2 allele resulted in significantly worse overall survival (OS; P = .028) and disease-free survival (DFS; P = .029) compared with other patients. Heavy drinkers with ALDH2*2 allele remained statistically significant in multivariate analysis for OS and DFS, indicating independent poor prognostic factor (hazard ratio [HR] 2.251; 95% confidence interval [CI] 1.018-4.975 and HR 2.261; 95% CI 1.021-5.006, respectively).

Conclusion: We conclude that heavy drinkers with the ALDH2*2 allele are associated with poor outcome in hypopharyngeal SCC.

Keywords: alcohol dehydrogenase-aldehyde dehydrogenase (ADH-ALDH) polymorphism; head and neck cancers; hypopharyngeal cancers; prognosis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Alcohol Dehydrogenase / genetics*
  • Alcohol Drinking / adverse effects*
  • Aldehyde Dehydrogenase / genetics*
  • Alleles
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cohort Studies
  • Disease-Free Survival
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypopharyngeal Neoplasms / genetics*
  • Hypopharyngeal Neoplasms / mortality
  • Hypopharyngeal Neoplasms / pathology
  • Hypopharyngeal Neoplasms / surgery
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis

Substances

  • Alcohol Dehydrogenase
  • Aldehyde Dehydrogenase