Cytochrome P450 1A1 genetic polymorphisms as cancer biomarkers.

ABSTRACT

Phase I metabolic enzyme CYP1A1 plays an important role in xenobiotics metabolism and has been extensively studied as a cancer risk biomarker. CYP1A1 is polymorphic and its four variants, e.g., CYP1A1* 2 A, CYP1A1* 2C, CYP1A1* 3 and CYP1A1* 4 with trivial names m1, m2, m3, and m4 respectively, are most commonly studied for cancer link. Gene‑ gene interaction studies combining polymorphisms of this enzyme with those of phase II detoxifying enzymes, especially glutathione S‑ transferases (GSTs) revealed greater risk for cancer susceptibility. Variants of CYP1A1 have also been found to be associated with chemotherapeutic adverse‑ effects. Results of these studies, however, remained largely contradictory mainly because of lack of statistical power due to involvement of small sample size. Strongly powered experimental designs involving gene‑ gene, gene‑ environment interactions are required in order to validate CYP1A1 as reliable cancer‑ biomarker.