Ben Boursi1,2,3, Harry J Han1, Kevin Haynes1, Ronac Mamtani1,2, Yu-Xiao Yang4. 1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 2. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. 3. Tel-Aviv University, Tel-Aviv, Israel. 4. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. yangy@mail.med.upenn.edu.
Abstract
PURPOSE: Mutations in ion channels are common among patients with glioblastoma multiforme (GBM) and promote cell migration and invasion. We sought to evaluate the association between the use of specific ion channel blockers such as digoxin, amiodarone, diltiazem and verapamil and GBM risk and survival. METHODS: We conducted a nested case-control study in a large primary care database from the UK. Cases were defined as all individuals with incident diagnosis of GBM during follow-up. For each case, up to four controls were selected using incidence density sampling. The primary exposure of interest was active treatment with each of the four ion channel blockers. We used conditional logistic regression to estimate odds ratios and 95% confidence interval (CI) for the association between ion channel blocker use and GBM risk. We then performed a Cox regression analysis among those diagnosed with GBM in order to evaluate the association between use of ion channel blockers and overall survival. Both analyses were adjusted to common confounders. RESULTS: The study included 1076 cases and 4253 matched controls. There was no statistically significant difference between cases and controls in cardiac and metabolic risk factors. There was no change in GBM risk in active users of ion channel blockers compared with non-users. Among patients with GBM, active users of amiodarone had worse survival compared with never users with an HR of 4.41 (95%CI 1.95-9.96). There was no statistically significant change in survival among diltiazem, verapamil or digoxin users. CONCLUSION: Treatment with specific ion channel blockers was not associated with the risk of GBM but was associated with worse survival in patients with GBM.
PURPOSE: Mutations in ion channels are common among patients with glioblastoma multiforme (GBM) and promote cell migration and invasion. We sought to evaluate the association between the use of specific ion channel blockers such as digoxin, amiodarone, diltiazem and verapamil and GBM risk and survival. METHODS: We conducted a nested case-control study in a large primary care database from the UK. Cases were defined as all individuals with incident diagnosis of GBM during follow-up. For each case, up to four controls were selected using incidence density sampling. The primary exposure of interest was active treatment with each of the four ion channel blockers. We used conditional logistic regression to estimate odds ratios and 95% confidence interval (CI) for the association between ion channel blocker use and GBM risk. We then performed a Cox regression analysis among those diagnosed with GBM in order to evaluate the association between use of ion channel blockers and overall survival. Both analyses were adjusted to common confounders. RESULTS: The study included 1076 cases and 4253 matched controls. There was no statistically significant difference between cases and controls in cardiac and metabolic risk factors. There was no change in GBM risk in active users of ion channel blockers compared with non-users. Among patients with GBM, active users of amiodarone had worse survival compared with never users with an HR of 4.41 (95%CI 1.95-9.96). There was no statistically significant change in survival among diltiazem, verapamil or digoxin users. CONCLUSION: Treatment with specific ion channel blockers was not associated with the risk of GBM but was associated with worse survival in patients with GBM.
Authors: James D Lewis; Rita Schinnar; Warren B Bilker; Xingmei Wang; Brian L Strom Journal: Pharmacoepidemiol Drug Saf Date: 2007-04 Impact factor: 2.890
Authors: Wanda H Vila-Carriles; Gergely Gy Kovacs; Biljana Jovov; Zhen-Hong Zhou; Amit K Pahwa; Garrett Colby; Ogenna Esimai; G Yancey Gillespie; Timothy B Mapstone; James M Markert; Catherine M Fuller; James K Bubien; Dale J Benos Journal: J Biol Chem Date: 2006-05-16 Impact factor: 5.157
Authors: Aiguo Li; Jennifer Walling; Yuri Kotliarov; Angela Center; Mary Ellen Steed; Susie J Ahn; Mark Rosenblum; Tom Mikkelsen; Jean Claude Zenklusen; Howard A Fine Journal: Mol Cancer Res Date: 2008-01-09 Impact factor: 5.852
Authors: Paola Ruggieri; Giorgio Mangino; Bernard Fioretti; Luigi Catacuzzeno; Rosa Puca; Donatella Ponti; Massimo Miscusi; Fabio Franciolini; Giuseppe Ragona; Antonella Calogero Journal: PLoS One Date: 2012-10-22 Impact factor: 3.240
Authors: G D'Alessandro; M Catalano; M Sciaccaluga; G Chece; R Cipriani; M Rosito; A Grimaldi; C Lauro; G Cantore; A Santoro; B Fioretti; F Franciolini; H Wulff; C Limatola Journal: Cell Death Dis Date: 2013-08-15 Impact factor: 8.469