Low Dose Exposure to Carcinogens and Metabolic Gene Polymorphisms

  • Emanuela Taioli
  • Seymour Garte
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 472)


Metabolic gene polymorphisms encode for enzymes which are involved in both metabolism and conjugation of environmental as well endogenous compounds. Some of the products of the metabolic process are carcinogens. Two main categories of metabolic genes are known: Phase I genes, which include CYP1A1, CYP2E1, CYP2D6, and Phase II genes, such as GSTM1, GSTT1, NAT2. Polymorphisms have been described in these genes, with different frequencies according to ethnicity and geographic area.1 Several case-control studies have been conducted to study the association between metabolic gene polymorphisms and cancer of various sites, with special focus on lung and bladder cancer. It has been suggested that these genes play a role in cancer risk only when they interact with environmental exposure, since the substrates of their gene products are xenobiotic chemicals or their metabolites.2 This form of gene-environment interaction (GEI) has been described as “Type 2” GEI by Khoury3 and Ottman.4 According to this model, the presence or absence of the genetic risk factor is irrelevant for disease causation, if there is no exposure to an environmental agent. When the dose of environmental exposure (such as smoking) is analyzed with respect to metabolic susceptibility gene polymorphisms, two patterns are seen. In one case, a low exposure-gene (LEG) effect is observed, in which a decreasing degree of interaction occurs as a function of increasing exposure dose. A high exposure-gene (HEG) effect is observed when there is an increased degree of interaction as a function of exposure dose.2


Genetic Risk Factor Lung Cancer Risk Sister Chromatid Exchange GSTM1 Null Genotype GSTM1 Genotype 
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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Emanuela Taioli
    • 1
  • Seymour Garte
    • 2
  1. 1.Policlinico IRCCS, University of MilanMilanItaly
  2. 2.EOHSI, UMDNJ-Robert Wood Johnson Medical SchoolPiscatawayUSA

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