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Genetic variation at the human MGMT locus and its biological consequences

Lookup NU author(s): Dr Mauro Santibanez Koref


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O6-alkylguanine-DNA alkyltransferase (MGMT) repairs DNA adducts that result from alkylation at the O6 position of guanine. These lesions are mutagenic and toxic and can be produced by a variety of agents ranging from carcinogens present in cigarette smoke to drugs used in cancer chemotherapy. There is a considerable amount of interindividual variation of MGMT activity and recent work has uncovered a series of polymorphisms that affect protein activity or are associated with differences in expression levels. On the other hand, current evidence for an association with cancer risk is tenuous: while some studies find such associations, others fail to support them. However, all published studies are based on small sample numbers. Not yet addressed are issues such as the relationship between sequence variation and the extent of the side effects of chemotherapy involving O6-alkylating agents. This review summarises the current state of knowledge in these areas. ©2006 Bentham Science Publishers Ltd.

Publication metadata

Author(s): Margison GP, Povey AC, Santibanez-Koref M

Publication type: Article

Publication status: Published

Journal: Current Pharmacogenomics

Year: 2006

Volume: 4

Issue: 2

Pages: 133-144

ISSN (print): 1570-1603

ISSN (electronic):

Publisher: Bentham Science Publishers


DOI: 10.2174/157016006776286873


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