Hypopharyngeal cancer risk in Japanese: Genetic polymorphisms related to the metabolism of alcohol- and tobacco-associated carcinogens

J Cancer Res Ther. 2019 Jul-Sep;15(3):556-563. doi: 10.4103/jcrt.JCRT_980_17.

Abstract

Background: Several studies have investigated hypopharyngeal cancer (HC) risk in combination with xenobiotic metabolism-related genetic polymorphisms and the burden of alcohol consumption and smoking in European countries but not in East Asian countries.

Patients and methods: This hospital-based case-control study involved 61 male patients with HC and 71 male cancer-free controls. Information on age, body mass index, and alcohol and cigarette consumption was obtained from medical records, a self-completion questionnaire, and a thorough interview by an otolaryngologist. Alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), cytochrome P450 A1 (CYP1A1) MspI, CYP1A1 Ile462Val, glutathione S-transferase (GST) M1, GSTT1, and GSTP1 gene polymorphisms were determined by polymerase chain reaction-based methods. Univariate and multivariate analyses were performed by adjustment for age by the Mantel-Haenszel method.

Results: The burden of alcohol and cigarette consumption significantly increased the risk of HC and showed a synergistic effect. ADH1B*1/*1 (odds ratio [OR] 7.34) and ALDH2 *1/*2 (OR 13.22) were significant risk factors for HC. Individuals with ADH1B*1/*1 or ALDH2 *1/*2 who consumed alcohol were more susceptible to HC. However, polymorphisms of CYP1A1 gene and GSTs were not significant cancer risk factors in patients with HC.

Conclusions: ADH1B*1/*1 and ALDH2 *1/*2 were significant risk factors for HC, while polymorphism of CYP1A1 gene and GSTs was not a significant risk factor for HC. These polymorphisms determined the effects of alcohol and cigarette smoke in addition to burden of alcohol and cigarettes intake on the risk of HC.

Keywords: Alcohol; cancer risk; hypopharyngeal cancer; polymorphism; tobacco smoke.

MeSH terms

  • Adult
  • Aged
  • Alcohol Dehydrogenase / genetics
  • Alcohol Dehydrogenase / metabolism
  • Alcohol Drinking / adverse effects
  • Aldehyde Dehydrogenase, Mitochondrial / genetics
  • Aldehyde Dehydrogenase, Mitochondrial / metabolism
  • Carcinogens
  • Case-Control Studies
  • Ethanol / metabolism
  • Female
  • Genotype
  • Humans
  • Hypopharyngeal Neoplasms / epidemiology*
  • Hypopharyngeal Neoplasms / etiology*
  • Hypopharyngeal Neoplasms / metabolism
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects

Substances

  • Carcinogens
  • Ethanol
  • ADH1B protein, human
  • Alcohol Dehydrogenase
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial