drug – gene interactions and colonic cancer protection

The excitement of the Dietary fibre story often came from the suggestion by Burkitt and Trowell that colonic cancer and dietary fibre intake were related. I have always been sceptical of this claim and would prefer to take aspirin as the evidence seemed to be stronger for this strategy.
Now this is challenged by J T Crosset al 2008 A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia The Pharmacogenomics Journal vol 8, 237–247;
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.
This review examines current evidence of gene–drug interactions between NSAID use and polymorphisms in COX1, COX2, ODC, UGT1A6 and CYP2C9 on risk of colorectal neoplasia.
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.

Martin Eastwood
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