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A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia.

Cross, James T. and Poole, Elizabeth M. and Ulrich, Cornelia M. (2008) A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia. The Pharmacogenomics Journal, 8 (4). pp. 237-247. ISSN 1473-1150

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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.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URL above.
DOI: 10.1038/sj.tpj.6500487
PubMed ID: 18195728
PMCID: PMC2603576
Grant Numbers: R01 CA114467-03, R03 CA123577-02, R25 CA094880-07, R25 CA092408-06
Keywords or MeSH Headings: Anti-Inflammatory Agents, Non-Steroidal/pharmacology/*therapeutic use; Colorectal Neoplasms/enzymology/*prevention & control; Drug Interactions/*genetics; Humans; Polymorphism, Genetic/drug effects/*genetics; Prostaglandin-Endoperoxide Synthases/genetics
Subjects: Diseases > Solid tumors > Digestive system cancer
Cellular and Organismal Processes > Genetic processes > Mutation
Therapeutics > Drug Therapy
Depositing User: Library Staff
Date Deposited: 30 Sep 2008 18:55
Last Modified: 14 Feb 2012 14:42

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