Syme R.,University of Calgary |
Carleton B.,Child and Family Research Institute of British Columbia |
Leyens L.,Maastricht University |
Richer E.,CIHR Institute of Genetics
Public Health Genomics | Year: 2015
There is currently a rapid evolution of clinical practices based on the introduction of patient stratification and molecular diagnosis that is likely to improve health outcomes. Building on a strong research base, complemented by strong support from clinicians and health authorities, the oncology field is at the forefront of this evolution. Yet, clinical research is still facing many challenges that need to be addressed in order to conduct necessary studies and effectively translate medical breakthroughs based on personalized medicine into standards of care. Leveraging its universal health care system and on resources developed to support oncology clinical research, Canada is well positioned to join the international efforts deployed to address these challenges. Available resources include a broad range of structures and funding mechanisms, ranging from direct clinical trial support to post-marketing surveillance. Here, we propose a clinical model for the introduction of innovation for precision medicine in oncology that starts with patients' and clinicians' unmet needs to initiate a cycle of discovery, validation, translation and sustainability development. © 2015 S. Karger AG, Basel. All rights reserved.
Mahlman M.,University of Oulu |
Huusko J.M.,University of Oulu |
Karjalainen M.K.,University of Oulu |
Kaukola T.,University of Oulu |
And 7 more authors.
Neonatology | Year: 2015
Background: Bronchopulmonary dysplasia (BPD) is one of the main consequences of prematurity, with notably high heritability. Vascular endothelial growth factor A (VEGF-A) and its main receptor, vascular endothelial growth factor receptor 2 (VEGFR-2), have been implicated in the pathogenesis of BPD. Objective: To study whether common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are associated with BPD. Methods: In this association study, six tagging single nucleotide polymorphism (tSNPs) for VEGFA and 25 tSNPs for VEGFR2 were genotyped in a prospectively collected, genetically homogeneous discovery population of 160 infants (44 infants with grade 2-3 BPD) born before 30 completed gestational weeks. The replication population of 328 infants included 120 cases of BPD. Results:VEGFR2 SNP rs4576072 was associated with BPD grade 2-3 with a minor allele frequency in 23.9% of the cases compared to 9.1% in controls (p = 0.0005, odds ratio 3.15, 95% CI: 1.62-6.12) in the discovery population. This association was not observed in the more heterogeneous replication population. Conclusions: In line with the results of recent large-scale genetic studies, our findings indicate that common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are not consistently associated with BPD. This finding does not rule out the involvement of VEGFA and VEGFR2 in BPD pathogenesis since, in addition to common variations within the gene region, other mechanisms also play important roles in the regulation of gene function. © 2015 S. Karger AG, Basel.
Huusko J.M.,University of Oulu |
Huusko J.M.,University of Turku |
Karjalainen M.K.,University of Oulu |
Karjalainen M.K.,University of Turku |
And 19 more authors.
BMC Medical Genetics | Year: 2014
Background: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease associated with very preterm birth. The major risk factors include lung inflammation and lung immaturity. In addition, genetic factors play an important role in susceptibility to moderate-to-severe BPD. In this study, the aim was to investigate whether common polymorphisms of specific genes that are involved in inflammation or differentiation of the lung have influence on BPD susceptibility. Methods: Genes encoding interleukin-6 (IL6) and its receptors (IL6R and IL6ST), IL-10 (IL10), tumor necrosis factor (TNF), and glucocorticoid receptor (NR3C1) were assessed for associations with moderate-to-severe BPD susceptibility. Five IL6, nine IL6R, four IL6ST, one IL10, two TNF, and 23 NR3C1 single nucleotide polymorphisms (SNPs) were analyzed in very preterm infants born in northern Finland (56 cases and 197 controls) and Canada (58 cases and 68 controls). IL-6, TNF and gp130 contents in umbilical cord blood, collected from very preterm infants, were studied for associations with the polymorphisms. Epistasis (i.e., interactions between SNPs in BPD susceptibility) was also examined. SNPs showing suggestive associations were analyzed in additional replication populations from Finland (39 cases and 188 controls) and Hungary (29 cases and 40 controls). Results: None of the studied SNPs were associated with BPD nor were the IL6, TNF or IL6ST SNPs associated with cord blood IL-6, TNF and gp130, respectively. However, epistasis analysis suggested that SNPs in IL6ST and IL10 were associated interactively with risk of BPD in the northern Finnish population; however, this finding did not remain significant after correction for multiple testing and the finding was not replicated in the other populations. Conclusions: We conclude that the analyzed SNPs within IL6, IL6R, IL6ST, IL10, TNF, and NR3C1 were not associated with BPD. Furthermore, there was no evidence that the studied SNPs directly contribute to the cord blood protein contents. © Huusko et al.; licensee BioMed Central Ltd.
Etminan M.,University of British Columbia |
Etminan M.,Child and Family Research Institute of British Columbia |
Brophy J.M.,McGill University |
Samii A.,University of Washington
Neurology | Year: 2014
Objective: To quantify the risk of peripheral neuropathy (PN) with oral fluoroquinolone (FQ) use. Methods: We conducted a case-control study within a cohort of men aged 45 to 80 years in the United States followed from 2001 to 2011. Cases were defined as those with the first physician visit diagnosis of PN, polyneuropathy, or drug-induced polyneuropathy. Four controls were matched to each case by age, follow-up, and calendar time using density-based sampling. As a sensitivity analysis, we also quantified the risk of PN with finasteride use, a drug that is not expected to increase the risk of PN. Rate ratios (RRs) for current users of FQs were computed using conditional logistic regression, which was adjusted for chronic renal failure, chronic liver disease, hypothyroidism, postherpetic neuralgia, and the use of nitrofurantoin and metronidazole. Results: We identified 6,226 cases and 24,904 controls. Current users of FQs were at a higher risk of developing PN (RR = 1.83, 95% confidence interval [CI] 1.49-2.27). Current new users had the highest risk (RR = 2.07, 95% CI 1.56-2.74). No risk was observed for current users of finasteride (RR = 1.21, 95% CI 0.97-1.51). Conclusions: Current users, especially new users of FQs, are at a higher risk of developing PN. Despite the increase in the use of FQs, clinicians should weigh the benefits against the risk of adverse events when prescribing these drugs to their patients. © 2014 American Academy of Neurology.
Forooghian F.,University of British Columbia |
Maberley D.,University of British Columbia |
Albiani D.A.,University of British Columbia |
Kirker A.W.,University of British Columbia |
And 2 more authors.
Ocular Immunology and Inflammation | Year: 2013
Objective: To determine the risk of uveitis associated with the use of oral fluoroquinolones. Methods: Nested case-control study of all patients who visited an ophthalmologist in British Columbia, Canada, between 2000 and 2007, as captured in the British Columbia Health Linked Database. Results: A total 3383 incident cases of uveitis and 33,830 corresponding controls were identified. Among patients who had used oral fluoroquinolones within the past 30 days, the adjusted relative risk of uveitis was 3.53 (95% CI, 2.84-4.39). However, the relative risk of uveitis among patients taking oral macrolides and beta-lactams was also significantly elevated. Conclusions: Our data do not provide convincing evidence of an association between fluoroquinolones and uveitis, as this study found an association between several classes of antibiotics and uveitis. It is possible that the systemic processes for which these antibiotics are being prescribed are in fact the inciting factors for the uveitis. © 2013 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.