Role of polymorphisms of biotransformation enzymes in colorectal cancer

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Klin Onkol 2005; 18(5): 188-193.

Abstract:

Background: Considering the proven significance of interplay between environmental and genetic factors in cancer, we aimed at determining whether any association exists between genetic polymorphisms in biotransformation enzymes and colorectal cancer (CRC).


Design and Subjects: Case-control study comprised of 314 CRC patients and 591 controls of Czech origin.


Methods and Results: Frequencies and distribution of polymorphisms in cytochrome P450 1B1, epoxide hydrolase, NAD(P)H: quinone oxidoreductase and glutathione S-transferase were followed by restriction analysis of PCR fragments. Statistical analysis showed:

  1. The lack of association of particular polymorphisms with CRC risk in unselected population.
  2. Female carriers of variant genotype in quinone oxidoreductase were at more than three-fold risk of CRC in comparison with those carrying normal genotype (P = 0.034). There was no association of this polymorphism with CRC risk in males, but its role in breast cancer was published in Czech and Austrian populations.
  3. The most interesting gene combinations seemed to be those comprising of glutathione S-transferases as associations of borderline significance were found (P < 0.1).
  4. Age played no role as confounding factor.


Conclusions: First study of this kind in Czech population showed that polymorphisms in biotransformation enzymes may affect onset of CRC. Further studies should be focused at searching for differences in exposure between genders, assessment of importance of larger selection of low penetrance genes and polymorphism combinations.

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