Nitrosamines, alcohol, and gastrointestinal tract cancer: recent epidemiology and experimentation

In Vivo. 1996 May-Jun;10(3):265-84.

Abstract

Recent epidemiological and experimental data continues to implicate nitrosamines in causation of gastrointestinal cancers. The evidence is strong for pharynx, esophagus, and stomach, and more problematic for liver, pancreas, and colorectum. Substantial levels of the promutagenic DNA adduct, Ob-methylguanine, in DNA from these organs in patas monkeys after a low dose of N-nitrosodimethylamine confirms the capacity for activation of environmental nitrosamines in these primate tissues. Alcohol is both an independent and a tobacco-interactive risk factor, influencing cancer incidence for oropharynx and esophagus strongly, and for stomach, colorectum, and liver more moderately. In a tabulation of experimental effects of ethanol potentially related to cancer-enhancing effects, toxicokinetic inhibition of hepatic first-pass clearance of nitrosamines is quantitatively greatest, and may be a major part of the mechanism of alcohol's effect on cancer risk for oropharnx, esophagus, and colon. Other operative mechanisms supported by experimental data are induction of activating enzymes, inhibition of DNA repair, and tumor promotion.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Animals
  • Carcinogens / adverse effects*
  • Drug Interactions
  • Gastrointestinal Neoplasms / chemically induced*
  • Gastrointestinal Neoplasms / epidemiology
  • Humans
  • Mouth Neoplasms / chemically induced
  • Nasopharyngeal Neoplasms / chemically induced
  • Nitrosamines / adverse effects*
  • Risk Factors

Substances

  • Carcinogens
  • Nitrosamines