Citations 2
A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer
Stegeman, Shane, Amankwah, Ernest K. , Klein, Kerenaftali, Kim, Donghwa , Lin, Hui‐Yi , Permuth‐Wey, Jennifer, Sellers, Thomas A. , Srinivasan, Srilakshmi , Eeles, Rosalind A. , Easton, Doug , Olama, Ali Amin Al , Benlloch, Sara, Muir, Kenneth , Wiklund, Fredrik, Grönberg, Henrik , Haiman, Christopher A. , Schleutker, Johanna , Nordestgaard, Børge G. , Travis, Ruth C. , Neal, David E. , Stanford, Janet L. , Blot, William J. , Thibodeau, Stephen N. , Maier, Christiane, Kibel, Adam S. , Brenner, Hermann , Kaneva, Radka , Teixeira, Manuel R. , BioResource, Australian Prostate Cancer, Clements, Judith A. , Batra, Jyotsna , Wahlfors, Tiina , Leongamornlert, Daniel , Southey, Melissa C. , Schumacher, Fredrick R. , Henrique, Rui , Hamdy, Freddie C. , Donovan, Jenny , Pashayan, Nora , Weischer, Maren , Saunders, Edward J. , Mitev, Vanio , Maia, Sofia , Tilley, Wayne D. , Thibodeau, Stephen, O’Mara, Tracy A. , Kote‐Jarai, Zsofia , Giles, Graham G. , Pharoah, Paul D.P. , Khaw, Kay‐Tee , Cybulski, Cezary , Cannon‐Albright, Lisa , BioResource, Australian Prostate Cancer, Spurdle, Amanda B. , Park, Jong Y. , Paulo, Paula , Teixeira, Manuel R , Eeles, Rosalind A , Southey, Melissa C , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Lin, Hui-Yi , Brenner, Hermann , Pinto, Pedro , Batra, Jyotsna , Clements, Judith
Cancer Discovery | February 17, 2015 | Volume: 5 | Issue: 4 | Pages: 368-379
Abstract Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3′ untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P < 2.3 × 10−5) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. Cancer Discov; 5(4); 368–79. ©2015 AACR. See related commentary by Yousef, p. 351 This article is highlighted in the In This Issue feature, p. 333
External Validation of a Multiplex Urinary Protein Panel for the Detection of Bladder Cancer in a Multicenter Cohort
Chen, Li-Mei, Chang, Myron, Dai, Yunfeng , Chai, Karl X., Dyrskjøt, Lars , Sänchez‐Carbayo, Marta, Szarvas, Tibor , Zwarthoff, Ellen C. , Lokeshwar, Vinata B. , Jerónimo, Cármen , Parker, Alexander S. , Ross, Shanti, Borre, Michael , Ørntoft, Torben F., Jaeger, T., Beukers, Willemien, López, Luis E., Henrique, Rui , Urquidi, Virginia, Goodison, Steve , Rosser, Charles J. , Chen, Li‐Mei , Young, Paul R.
Cancer Epidemiology, Biomarkers & Prevention | June 12, 2014 | Volume: 23 | Issue: 9 | Pages: 1804-1812
Abstract Background: Because of the faltering sensitivity and/or specificity, urine-based assays currently have a limited role in the management of patients with bladder cancer. The aim of this study was to externally validate our previously reported protein biomarker panel from multiple sites in the United States and Europe. Methods: This multicenter external validation study included a total of 320 subjects (bladder cancer = 183). The 10 biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SDC1, and SERPINE1) were measured using commercial ELISA assays in an external laboratory. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values. Results: Utilizing the combination of all 10 biomarkers, the area under the ROC for the diagnostic panel was noted to be 0.847 (95% confidence interval, 0.796–0.899), outperforming any single biomarker. The multiplex assay at optimal cutoff value achieved an overall sensitivity of 0.79, specificity of 0.79, positive prediction value of 0.73, and negative prediction value of 0.84 for bladder cancer classification. Sensitivity values of the diagnostic panel for high-grade bladder cancer, low-grade bladder cancer, muscle invasive bladder cancer, and non-muscle invasive bladder cancer were 0.81, 0.90, 0.95, and 0.77, respectively. Conclusions: Urinary levels of the biomarker panel enabled discrimination of patients with bladder cancer and controls, and the levels of biomarker subsets were associated with advancing tumor grade and stage. Impact: If proven to be reliable, urinary diagnostic biomarker assays can detect bladder cancer in a timely manner such that the patient can expect improvements in overall survival and quality of life. Cancer Epidemiol Biomarkers Prev; 23(9); 1804–12. ©2014 AACR.