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A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia
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A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia
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Journal Article
A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia
2008
Overview
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents for colorectal neoplasia. Polymorphisms in NSAID targets or metabolizing enzymes may affect NSAID efficacy or toxicity. We conducted a literature review to summarize current evidence of gene–drug interactions between NSAID use and polymorphisms in
COX1
,
COX2
,
ODC
,
UGT1A6
and
CYP2C9
on risk of colorectal neoplasia by searching OVID and PubMed. Of 134 relevant search results, thirteen investigated an interaction. One study reported a significant interaction between NSAID use and the
COX1
Pro17Leu polymorphism (
P
=0.03) whereby the risk reduction associated with NSAID use among homozygous wild-type genotypes was not observed among NSAID users with variant alleles. Recent pharmacodynamic data support the potential for gene–drug interactions for
COX1
Pro17Leu. Statistically significant interactions have also been reported for
ODC
(315G>A),
UGT1A6
(Thr181Ala+Arg184Ser or Arg184Ser alone), and
CYP2C9
(
*
2/
*
3). No statistically significant interactions have been reported for polymorphisms in
COX2
; however, an interaction with
COX2
−765G>C approached significance (
P
=0.07) in one study. Among seven remaining studies, reported interactions were not statistically significant for
COX1
,
COX2
and
ODC
gene polymorphisms. Most studies were of limited sample size. Definitions of NSAID use differed substantially between studies. The literature on NSAID–gene interactions to date is limited. Reliable detection of gene–NSAID interactions will require greater sample sizes, consistent definitions of NSAID use and evaluation of clinical trial subjects of chemoprevention studies.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
/ Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
/ Biomedical and Life Sciences
/ Colorectal Neoplasms - enzymology
/ Colorectal Neoplasms - prevention & control
/ Drug Interactions - genetics
/ Humans
/ Nonsteroidal anti-inflammatory drugs
/ Oncology
/ Polymorphism, Genetic - drug effects
/ Polymorphism, Genetic - genetics
/ Prostaglandin-Endoperoxide Synthases - genetics
/ review
/ Toxicity
