|
|
|
DESCRIPTION
The P-450II family comprises at least 5 subfamilies, designated A through E by the system of
nomenclature recommended by an international committee. The P450IID subfamily comprises at least 2
genes in the rat, one of which is highly specific for debrisoquine 4-hydroxylase activity. The literature is
growing that confirms the association of this gene with lung cancer. Enhanced CYP2D6 activity has been
related to malignancies of the bladder, liver, pharynx, and stomach and, especially, to cigarette-smoking-
induced lung cancer. The data suggest that enhanced CYP2D6-mediated metabolism of one or more dietary
and other environmental agents, to form a reactive intermediate, plays a role in cancer initiation and/or
promotion in various tissues. Reduced CYP2D6 activity resulting in the 'poor metabolizer' phenotype has
been thought to be related to an increased risk of Parkinson disease.
CYP2D6 polymorphism, which is responsible for the variation in metabolism of debrisoquine
4-hydroxylase, is important in the metabolism of more than 30 drugs and environmental chemicals,
including as much as 20% of all commonly prescribed drugs. Although humans probably have
approximately 60 unique P450 genes, only approximately a half dozen appear to be responsible for
metabolism of the vast majority of prescribed and over-the-counter drugs: CYP1A2, CYP2C17,CYP2D6,
CYP2E1, CYP3A4, and CYP4A11.