Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal cancer risk

Am J Clin Nutr. 2010 Mar;91(3):704-11. doi: 10.3945/ajcn.2009.28683. Epub 2009 Dec 30.

Abstract

Background: Isothiocyanates, compounds found primarily in cruciferous vegetables, have been shown in laboratory studies to possess anticarcinogenic activity. Glutathione S-transferases (GSTs) are involved in the metabolism and elimination of isothiocyanates; thus, genetic variations in these enzymes may affect in vivo bioavailability and the activity of isothiocyanates.

Objective: The objective was to prospectively evaluate the association between urinary isothiocyanate concentrations and colorectal cancer risk as well as the potential modifying effect of GST genotypes on the association.

Design: A nested case-control study of 322 cases and 1251 controls identified from the Shanghai Women's Health Study was conducted.

Results: Urinary isothiocyanate concentrations were inversely associated with colorectal cancer risk; the inverse association was statistically significant or nearly significant in the GSTM1-null (P for trend = 0.04) and the GSTT1-null (P for trend = 0.07) genotype groups. The strongest inverse association was found among individuals with both the GSTM1-null and the GSTT1-null genotypes, with an adjusted odds ratio of 0.51 (95% CI: 0.27, 0.95), in a comparison of the highest with the lowest tertile of urinary isothiocyanates. No apparent associations between isothiocyanate concentration and colorectal cancer risk were found among individuals who carried either the GSTM1 or GSTT1 gene (P for interaction < 0.05).

Conclusion: This study suggests that isothiocyanate exposure may reduce the risk of colorectal cancer, and this protective effect may be modified by the GSTM1 and GSTT1 genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Biological Availability
  • Brassicaceae / chemistry*
  • Case-Control Studies
  • China
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / urine
  • Diet*
  • Female
  • Glutathione Transferase / genetics*
  • Humans
  • Isothiocyanates / urine*
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Risk Factors
  • Vegetables / chemistry

Substances

  • Isothiocyanates
  • isothiocyanic acid
  • Glutathione Transferase