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Combinations of Cytochrome P450 Gene Polymorphisms Enhancing the Risk for Sporadic Colorectal Cancer Related to Red Meat Consumption
Ist Teil von
Cancer epidemiology, biomarkers & prevention, 2007-07, Vol.16 (7), p.1460-1467
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2007
Quelle
Electronic Journals Library
Beschreibungen/Notizen
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. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1460–7)