Thursday, May 3, 2012

How might genetic variants of a single gene affect addiction to cigarettes and response to anti-cancer therapy?

Nicotine - one of the many substrates of CYP2A6
The human CYP2A6 enzyme is involved in the metabolism of many different compounds - including  those found in our diet and therapeutic drugs. We have recently written an updated Very Important Pharmacogene (VIP) Summary that is published in Pharmacogenetics and Genomics.

CYP2A6 has a major role in the metabolism of nicotine, and variants of the CYP2A6 gene have been associated with extent of nicotine metabolism and cigarette smoking behaviors. Individuals who have the CYP2A6*2, *4, *9 and *12 alleles, show reduced metabolism of nicotine (they are "slow metabolizers" of nicotine) and smoke fewer cigarettes per day, take smaller puffs, and find it easier to quit smoking than individuals who have normal metabolism of nicotine (see the CYP2A6 VIP summary for references and more details).

CYP2A6 also has a role in the conversion of the prodrug tegafur into 5-fluorouracil (5 FU), a compound that is broken down to metabolites that have anti-cancer properties (see the Pharmacokinetic and Pharmacodynamic pathways). Several CYP2A6 variants (such as *4, *7, *9 alleles) that have been shown to result in reduced metabolism of tegafur, have separately been associated with lower anti-cancer therapy response rates and increased risk of disease progression (see the CYP2A6 VIP summary for references and more details).

Find out more...
View our new CYP2A6 VIP Summary www.pharmgkb/vip/PA121 with links to variants, haplotypes, drugs and publications.

Read our new CYP2A6 VIP Summary publication.
PharmGKB summary: very important pharmacogene information for cytochrome P-450, family 2, subfamily A, polypeptide 6. McDonagh EM and Wassenaar C (co-first authors), David SP, Tyndale RF, Altman RB, Whirl-Carrillo M, Klein TE. Pharmacogenet Genomics. 2012 Apr 26 (Epub ahead of print).