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

The Pharmacogenomics Journal volume 8, pages 237–247 (2008)Cite this article

Abstract

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.

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Abbreviations

CI:

confidence interval

COX:

cyclooxygenase

NSAIDs:

nonsteroidal anti-inflammatory drugs

ODC:

ornithine decarboxylase

OR:

odds ratio

PTGS1:

prostaglandin H synthase1

PTGS2:

prostaglandin H synthase 2

hzv:

homozygous variant

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Acknowledgements

Work was supported by grants from the National Institutes of Health R01 CA114467; R03 CA123577; R25 CA094880 and R25 CA092408-06. We thank Rachel Galbraith for her technical assistance with the article.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    J T Cross, E M Poole & C M Ulrich

  2. Department of Pharmacy, University of Washington, Seattle, WA, USA

    J T Cross

  3. Department of Epidemiology, University of Washington, Seattle, WA, USA

    E M Poole & C M Ulrich

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Correspondence to C M Ulrich.

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Cross, J., Poole, E. & Ulrich, C. A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia. Pharmacogenomics J 8, 237–247 (2008). https://doi.org/10.1038/sj.tpj.6500487

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