Docetaxel-induced neuropathy:A pharmacogenetic case-control study of 150 women with early-stage breast cancer

<div><p></p><p><b>Background.</b> Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in <i>GSTP1</i> and <i>ABCB1</i> on DIPN.</p><p><b>Material and methods.</b> DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two polymorphisms in <i>GSTP1</i> and three in <i>ABCB1</i> were selected for the primary analysis, and a host of other candidate genes was explored and compared between 75 patients with clinician-reported DIPN grade ≥ 2 and 75 patients without DIPN.</p><p><b>Results.</b> Patients with the genetic variants <i>GSTP1</i> rs1138272 C/T or T/T (114Ala/114Val or 114Val/114Val) genotype had an adjusted odds ratio of 3.82; 95% confidence interval 1.34–11.09 of developing DIPN. This result was confirmed in both analysis of cumulated docetaxel dose and haplotype analysis. None of the explorative genes investigated were significantly correlated with DIPN. Patients with a BMI ≥ 30 were five-fold more likely to have DIPN than patients with BMI < 25.</p><p><b>Conclusion.</b> We found that <i>GSTP1</i> Ala114Val polymorphism is associated with occurrence of DIPN. This supports the theory that oxidative stress is involved in DIPN pathophysiology. If confirmed, this may be helpful in the risk assessment of DIPN and perhaps help to achieve better management of neurotoxicity.</p></div

No detectable differential microRNA expression between non-atherosclerotic arteries of type 2 diabetic patients (treated or untreated with metformin) and non-diabetic patients

Abstract Background Type 2 diabetes mellitus (T2DM) is an independent risk factor of cardiovascular disease (CVD), however, the underlying mechanisms are largely unknown. Using non-atherosclerotic internal thoracic arteries (ITAs) obtained from coronary artery bypass grafting, we previously identified a distinct elevation in the level of proteins comprising the arterial basement membrane in T2DM patients not treated with metformin. Altered transcription of genes encoding these proteins has not been observed, indicating alternative mechanisms of dysregulation. Methods In this study we screened for differential expression of arterial microRNAs (miRNAs) in T2DM patients to test the hypothesis that the arterial protein signature of diabetic patients is associated with dysregulation at the miRNA level, and further to lay the foundation for novel hypotheses addressing the increased CVD risk of T2DM patients. MiRNA isolated from fresh frozen ITAs [from 18 T2DM- (10 of which were subject to metformin treatment) and 30 non-diabetes mellitus (non-DM) patients] were analyzed by microarray, and miRNAs isolated from formalin-fixated paraffin-embedded (FFPE) ITAs were analyzed by quantitative PCR (qPCR) in an independent study group [26 T2DM- (15 of which were subject to metformin treatment) and 26 non-DM patients] to determine expression levels of miRNAs in a pre-defined panel of 12 miRNAs. Results Unexpectedly, no miRNAs were found to be affected by T2DM status in either of the two study groups. Conclusions Our data suggest that alternatives to microRNA dysregulation underlie T2DM-associated protein changes in non-atherosclerotic arteries

MOESM1 of No detectable differential microRNA expression between non-atherosclerotic arteries of type 2 diabetic patients (treated or untreated with metformin) and non-diabetic patients

Additional file 1. MicroRNA microarray results. MicroRNA microarray data analysis for 677 probes comparing (1) T2DM vs. non-DM patients, (2) T2DM (− Met) vs. non-DM patients, and (3) T2DM (+ Met) vs. T2DM (− Met)