Clinical use of pharmacogenomic tests in 2009.

Pharmacogenomics is a new field where testing an individual can define either a risk status for an adverse event, or the rate of metabolism of a drug. This is achieved by the categorisation of the enzyme activity or documenting genetic polymorphisms of a metabolising enzyme. The best example of risk status assessment is the recent finding that HLA-B typing a person can predict whether they are at risk of a severe skin reaction from the drug abacavir. Those patients showing HLA-B*5701, who are being considered for abacavir therapy, can be prevented from developing potentially toxic epidermal necrosis (TEN) or Stevens-Johnson Syndrome by avoiding abacavir. The evidence for HLA-B typing for allopurinol and carbamazepine has also been described. Most other pharmacogenomic tests are of drug metabolising enzymes, which can either be assessed using "probe" drugs and measuring a ratio of parent drug to metabolite, or, by genetic testing for polymorphisms of the genes. In practice, testing is usually done by molecular testing, but this typically does not detect all polymorphisms. This article briefly reviews the evidence for the utilisation of pharmacogenomics for antidepressant drugs, tamoxifen, codeine, warfarin, azathioprine, clopidogrel, omeprazole, tacrolimus and irinotecan. There are few pharmacogenomics tests being carried out in practice, as there has not been a wide appreciation of their use, and only limited evidence exists for many individual drugs. It is expected that utilisation will increase as more evidence becomes available and there is a wider understanding of the existing evidence by the medical profession.

Thiopurine methyltransferase and thiopurine metabolite testing in patients with inflammatory bowel disease who are taking thiopurine drugs.

Thiopurine methyltransferase genotyping and thiopurine metabolite testing has been established as an adjunct to monitoring patients taking thiopurine drugs. This special report describes the clinical implications for this type of testing for patients with inflammatory bowel disease who are taking thiopurine drugs. A total of 10% of patients were found to be intermediate metabolizers and the mean dosage (in mg/kg equivalent) was lower in intermediate metabolizers than extensive metabolizers. The metabolite levels did not correlate with scores measuring clinical severity but levels of 6-methylmercaptopurine were related to the dosage of the drugs. Despite considerable study of thiopurine methyltransferase testing in the literature, it is still not widely used in many geographical areas. This study adds to the evidence about using such testing as well as expanding the role of simultaneously measuring thiopurine metabolites. Further work is planned to evaluate the uptake when such testing becomes available locally as a clinical service.

Analysis of familial male breast cancer for germline mutations in CHEK2.

We have previously shown that the1100delC variant of the cell-cycle-checkpoint kinase gene CHEK2, which is carried by approximately 1% of the population confers a two-fold increase in female breast cancer and a 10-fold increase in male breast cancer. To extend our knowledge on the role of CHEK2 in susceptibility to male breast cancer we have screened a series of 26 breast cancer cases with male representation for germline sequence variation in the CHEK2 gene. One individual was found to harbour the 1100delC variant. No other mutations were identified. Variants other than 1100delC are rare in male breast cancer.