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Keywords:

  • NQO1;
  • NFE2L2;
  • polymorphisms;
  • lifestyle factors;
  • colorectal adenomas

Abstract

Both environment and genetics contribute to the pathogenesis and prevention of colorectal neoplasia. NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that is polymorphic and inducible. We investigated interactions between lifestyle factors and polymorphisms in NQO1 and its key regulatory transcription factor NFE2L2 in colorectal adenoma risk. The NQO1 c.609C>T and g.-718A>G and NFE2L2 g.-650C>A, g.-684G>A and g.-686A>G polymorphisms were determined among 740 Dutch adenoma cases and 698 endoscopy-based controls. Dietary intake was assessed by food frequency questionnaire, other lifestyle information by questionnaire. The NQO1 609CT genotype was associated with a higher adenoma risk (OR 1.27, 95% CI 1.00–1.62) compared with the 609CC genotype, whereas the 609TT genotype was not (OR 1.03, 95% CI 0.56–1.88). The higher risk with the NQO1 609CT-genotype was seen among smokers (OR 1.96, 95% CI 1.40–2.76), but not among nonsmokers (OR 0.91, 95% CI 0.62–1.35; interaction p = 0.030). Fruit and vegetable consumption did not protect smokers from adenomas and did not interact with the NQO1 609C>T polymorphism or the NFE2L2 polymorphisms. A higher adenoma risk seen with high fruit and vegetable consumption among NQO1 -718GG genotypes was absent among -718GA genotypes (interaction p = 0.071). Gene–gene interactions were observed between the NQO1 609C>T and NFE2L2 -686A>G polymorphisms (interaction p = 0.056) and between the NQO1 -718 G>A and NFE2L2 -650C>A polymorphisms (interaction p = 0.013). In conclusion: the NQO1 609CT genotype is associated with increased adenoma risk among smokers, which is not diminished by high fruit and vegetable consumption. The observed gene–gene interactions may point to a role for NFE2L2 polymorphisms in NQO1-related adenoma formation. © 2007 Wiley-Liss, Inc.