Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting

The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival

The PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the estrogen receptor-1 (ESR1), has been found associated with outcome in tamoxifen treated patients with early hormone-receptor positive breast cancer. However, it remains unclear whether this SNP is a predictive marker for tamoxifen efficacy or a prognostic marker for breast cancer outcome. The aim of this study was to examine the prognostic potential of this SNP in postmenopausal early breast cancer patients treated with adjuvant exemestane. Dutch postmenopausal patients randomised to 5 years of adjuvant exemestane of whom tissue was available (N=807) were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial database. The SNP rs2234693 in the ESR1 gene was genotyped on DNA from formalin-fixed paraffin embedded (FFPE) tumor tissue using Taqman assays and related to the primary endpoint disease-free survival (DFS) and secondary endpoint overall survival (OS). Survival analyses were performed using Cox regression analysis. In total 805 patients were included in the analyses (median follow up of 5.22 years) and genotypes were obtained in 97% of the samples. The variant T allele of PvuII in ESR1 (rs2234693) was associated with a better DFS (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.480-0.989, P=0.044) in univariate analysis only, and a better OS in both univariate (HR 0.616, 95%, CI 0.411-0.923, P=0.019) and multivariate analyses (HR 0.571, 95% CI 0.380-0.856, P=0.007), consistent with a prognostic rather than a predictive drug response effect. Variation of PvuII in the ESR1 gene is related to OS in postmenopausal, early HR+breast cancer patients treated with exemestane in the TEAM study. Variation in the ESR1 gene may therefore be a prognostic marker of early breast cancer survival, and warrants further research.Surgical oncolog

A novel specific pyrosequencing method for genotyping FCGR3A rs396991 without coamplification of homologous gene FCGR3B

Personalised Therapeutic

Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery

Recent studies suggest that high lipoprotein(a) [Lp(a)] plasma levels are associated with symptomatic ischemic cardiovascular disease. We examined whether Lp(a) plasma levels are associated with early atherosclerotic vessel wall changes in a group of asymptomatic subjects. In a group of 142 asymptomatic men, the intima-media thickness (IMT) in the common carotid artery, the carotid bifurcation and the common femoral artery was determined by B-mode ultrasonography. In addition to Lp(a) levels, established risk factors, such as blood pressure and cholesterol levels were determined. Lipoprotein(a) values ranged from 2 mg L(-1) to 900 mg L(-1) (median 145 mg L(-1)). Linear regression analysis showed a clear association of IMT with the established risk factors but not with Lp(a) [regression coefficient carotid artery -0.0003, 95% confidence interval (CI) -0.002-0.001; regression coefficient femoral artery -0.0003, 95% CI -0.004-0.003]. We found no increased intima-media thickness in the carotid or femoral artery at high levels of Lp(a). Lipoprotein(a) levels are not associated with early atherosclerotic vessel wall changes in the carotid or femoral arter

A pilot study of the implementation of pharmacogenomic pharmacist initiated pre-emptive testing in primary care

Despite the nationwide availability of pharmacogenomic (PGx) guidelines in electronic medication surveillance systems in The Netherlands, PGx guided prescribing is still uncommon in primary care. We set out to investigate the adoption of pharmacist initiated PGx testing in primary care. Community pharmacists were offered a free PGx test covering 40 variants in 8 genes to test patients receiving an incident prescription (IRx) of a selection of 10 drugs. Results of the PGx test along with predicted phenotypes and a therapeutic recommendation based on the Dutch Pharmacogenetics Working Group (DPWG) guidelines were transferred to the pharmacist and physician. Adoption was defined as the percentage of eligible patients that received genotyping. From November 2014-July 2016, 200 patients were included with an adoption of 18.0%. Of the included patients 57.5% received an IRx for atorvastatin, 14.5% started with simvastatin and 28.0% received an IRx for amitriptyline, (es)citalopram, nortriptyline, or venlafaxine. 90% of the patients carried at least one actionable PGx test result in the selected PGx-panel. In 31.0% of the incident prescriptions a combination between a drug with a known genedrug interaction and an actionable genotype was present and a therapeutic recommendation was provided. The provided recommendations were accepted by the clinicians in 88.7% of the patients Pharmacist initiated implementation of PGx in primary care is feasible, and the frequency of actionable gene-drug interactions for the selected drugs is high.Personalised Therapeutic

Pharmacogenetics in Transplant Patients: Mind the Mix

Personalised Therapeutic

Variation in the ESR-1 gene as a prognostic marker in early breast cancer survival

Experimentele farmacotherapi

FcGR genetic polymorphisms and the response to adalimumab in patients with rheumatoid arthritis

Pathophysiology and treatment of rheumatic disease

Association of polymorphisms in IL-12/IFN-gamma pathway genes with susceptibility to pulmonary tuberculosis in Indonesia.

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