Donovan, Jenny L
Mayo Clinic
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
Citations 12
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
Multiple Novel Prostate Cancer Predisposition Loci Confirmed by an International Study: The PRACTICAL Consortium
Easton, Douglas F. , Stanford, Janet L. , Ostrander, Elaine A. , Schleutker, Johanna , Schaid, Daniel J. , Thibodeau, Stephen N. , Dörk, Thilo , Neal, David E. , Cox, Angela , Maier, Christiane, Guy, Michelle, Lophatananon, Artitaya, Kedda, Mary-Anne, Spurdle, Amanda B. , Steginga, Suzanne K., John, Esther M. , Giles, Graham G. , Chappuis, Pierre O. , Hutter, Pierre, Foulkes, William D. , Hamel, Nancy , Salinas, Claudia A., Karyadi, Danielle M. , Johanneson, Bo, Wahlfors, Tiina , Tammela, Teuvo L.J. , Corral, Román, McDonnell, Shannon K. , Schürmann, Peter , Meyer, Andreas , Kuefer, Rainer, Leongamornlert, Daniel , Tymrakiewicz, Malgorzata, Liu, Jo‐Fen , O’Mara, Tracy A. , Gardiner, Robert A. , Aitken, Joanne F. , Joshi, Amit D. , Severi, Gianluca , English, Dallas R. , Southey, Melissa C. , Edwards, Stephen M., Olama, Ali Amin Al , Eeles, Rosalind A. , Donovan, Jenny , Chambers, Suzanne K. , Kote‐Jarai, Zsofia , Ingles, Sue A. , Vogel, W. , Muir, Kenneth , Hopper, John L. , Koopmeiners, Joseph Stephen , Stern, Mariana Carla , Dörk, Thilo , Giles, Graham G , Spurdle, Amanda B , Foulkes, William D , Eeles, Rosalind A , John, Esther M , Southey, Melissa C , English, Dallas R , Donovan, Jenny L , Schleutker, Johanna , O'Mara, Tracy A , Cox, Angela , Severi, Gianluca , McDonnell, Shannon K
Cancer Epidemiology, Biomarkers & Prevention | August 15, 2008 | Volume: 17 | Issue: 8 | Pages: 2052-2061
Abstract A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10−17). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2052–61)