Combinations of cytochrome P450 gene polymorphisms enhancing the risk for sporadic colorectal cancer related to red meat consumption. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Epidemiology, Biomarkers and Prevention Année : 2007

Combinations of cytochrome P450 gene polymorphisms enhancing the risk for sporadic colorectal cancer related to red meat consumption.

Sébastien Küry
  • Fonction : Auteur
Bruno Buecher
  • Fonction : Auteur
Sébastien Robiou-Du-Pont
  • Fonction : Auteur
Catherine Scoul
  • Fonction : Auteur
Hélène Colman
  • Fonction : Auteur
Claire Le Houérou
  • Fonction : Auteur
Roger Faroux
  • Fonction : Auteur
Jean Ollivry
  • Fonction : Auteur
Bernard Lafraise
  • Fonction : Auteur
Stéphane Bézieau

Résumé

Susceptibility to sporadic colorectal cancers (CRC) is generally thought to be the sum of complex interactions between environmental and genetic factors, all of which contribute independently, producing only a modest effect on the whole phenomenon. However, to date, most research has concealed the notion of interaction and merely focused on dissociate analyses of risk factors to highlight associations with CRC. By contrast, we have chosen a combinative approach here to explore the joint effects of several factors at a time. Through an association study based on 1,023 cases and 1,121 controls, we examined the influence on CRC risk of environmental factors coanalyzed with combinations of six single nucleotide polymorphisms located in cytochrome P450 genes (c.-163A>C and c.1548T>C in CYP1A2, g.-1293G>C and g.-1053C>T in CYP2E1, c.1294C>G in CYP1B1, and c.430C>T in CYP2C9). Whereas separate analyses of the SNPs showed no effect on CRC risk, three allelic variant combinations were found to be associated with a significant increase in CRC risk in interaction with an excessive red meat consumption, thereby exacerbating the intrinsic procarcinogenic effect of this dietary factor. One of these three predisposing combinations was also shown to interact positively with obesity. Provided that they are validated, our results suggest the need to develop robust combinative methods to improve genetic investigations into the susceptibility to CRC.
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Dates et versions

hal-00415938 , version 1 (11-09-2009)

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Sébastien Küry, Bruno Buecher, Sébastien Robiou-Du-Pont, Catherine Scoul, Véronique Sébille, et al.. Combinations of cytochrome P450 gene polymorphisms enhancing the risk for sporadic colorectal cancer related to red meat consumption.. Cancer Epidemiology, Biomarkers and Prevention, 2007, 16 (7), pp.1460-7. ⟨10.1158/1055-9965.EPI-07-0236⟩. ⟨hal-00415938⟩
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