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7 results on '"Tyrer, Jonathan P"'

1. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci

Author

Coetzee, Simon G, Shen, Howard C, Hazelett, Dennis J, Lawrenson, Kate, Kuchenbaecker, Karoline, Tyrer, Jonathan, Rhie, Suhn K, Levanon, Keren, Karst, Alison, Drapkin, Ronny, Ramus, Susan J, Consortium, The Consortium of Investigators of Modifiers of BRCA1 2 The Ovarian Cancer Association, Couch, Fergus J, Offit, Kenneth, Chenevix-Trench, Georgia, Monteiro, Alvaro NA, Antoniou, Antonis, Freedman, Matthew, Coetzee, Gerhard A, Pharoah, Paul DP, Noushmehr, Houtan, Gayther, Simon A, Anton-Culver, Hoda, Antonenkova, Natalia, Baker, Helen, Bandera, Elisa V, Bean, Yukie, Beckmann, Matthias W, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Chen, Ann, Chen, Zhihua, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Easton, Douglas F, Edwards, Robert P, Eilber, Ursula, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Grownwald, Jacek, Harrington, Patricia, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, James, Paul, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kjaer, Susanne Kruger, Kelemen, Linda E, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, and Lissowska, Jolanta

Subjects
Biological Sciences, Genetics, Rare Diseases, Prevention, Human Genome, Ovarian Cancer, Biotechnology, Cancer, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Chromatin, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Histones, Humans, Organ Specificity, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Ovarian Cancer Association Consortium, The Consortium of Investigators of Modifiers of BRCA1/2, Ovarian Cancer Association Consortium The Consortium of Investigators of Modifiers of BRCA1/2, Medical and Health Sciences, Genetics & Heredity
Abstract

Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.

Published
2015

2. Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

Author

Painter, Jodie N, O'Mara, Tracy A, Batra, Jyotsna, Cheng, Timothy, Lose, Felicity A, Dennis, Joe, Michailidou, Kyriaki, Tyrer, Jonathan P, Ahmed, Shahana, Ferguson, Kaltin, Healey, Catherine S, Kaufmann, Susanne, Hillman, Kristine M, Walpole, Carina, Moya, Leire, Pollock, Pamela, Jones, Angela, Howarth, Kimberley, Martin, Lynn, Gorman, Maggie, Hodgson, Shirley, De Polanco, Ma Magdalena Echeverry, Sans, Monica, Carracedo, Angel, Castellvi-Bel, Sergi, Rojas-Martinez, Augusto, Santos, Erika, Teixeira, Manuel R, Carvajal-Carmona, Luis, Shu, Xiao-Ou, Long, Jirong, Zheng, Wei, Xiang, Yong-Bing, Montgomery, Grant W, Webb, Penelope M, Scott, Rodney J, McEvoy, Mark, Attia, John, Holliday, Elizabeth, Martin, Nicholas G, Nyholt, Dale R, Henders, Anjali K, Fasching, Peter A, Hein, Alexander, Beckmann, Matthias W, Renner, Stefan P, Dörk, Thilo, Hillemanns, Peter, Dürst, Matthias, Runnebaum, Ingo, Lambrechts, Diether, Coenegrachts, Lieve, Schrauwen, Stefanie, Amant, Frederic, Winterhoff, Boris, Dowdy, Sean C, Goode, Ellen L, Teoman, Attila, Salvesen, Helga B, Trovik, Jone, Njolstad, Tormund S, Werner, Henrica MJ, Ashton, Katie, Proietto, Tony, Otton, Geoffrey, Tzortzatos, Gerasimos, Mints, Miriam, Tham, Emma, Hall, Per, Czene, Kamila, Liu, Jianjun, Li, Jingmei, Hopper, John L, Southey, Melissa C, Ekici, Arif B, Ruebner, Matthias, Johnson, Nicola, Peto, Julian, Burwinkel, Barbara, Marme, Frederik, Brenner, Hermann, Dieffenbach, Aida K, Meindl, Alfons, Brauch, Hiltrud, Lindblom, Annika, Depreeuw, Jeroen, Moisse, Matthieu, Chang-Claude, Jenny, Rudolph, Anja, Couch, Fergus J, Olson, Janet E, Giles, Graham G, Bruinsma, Fiona, Cunningham, Julie M, Fridley, Brooke L, Børresen-Dale, Anne-Lise, Kristensen, Vessela N, Cox, Angela, Swerdlow, Anthony J, and Orr, Nicholas

Subjects
Cancer, Biotechnology, Human Genome, Prevention, Genetics, 2.1 Biological and endogenous factors, Aetiology, Alleles, Case-Control Studies, Cell Line, Tumor, Chromosome Mapping, Computational Biology, Databases, Genetic, Endometrial Neoplasms, Epigenesis, Genetic, Female, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Genotype, Haplotypes, Hepatocyte Nuclear Factor 1-beta, Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, RNA, Messenger, Risk Factors, White People, National Study of Endometrial Cancer Genetics Group, CHIBCHA Consortium, Australian National Endometrial Cancer Study Group, RENDOCAS, Australian Ovarian Cancer Study, GENICA Network, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

Published
2015

3. A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium.

Author

Milne, Roger, Herranz, Jesús, Michailidou, Kyriaki, Dennis, Joe, Tyrer, Jonathan, Zamora, M, Arias-Perez, José, González-Neira, Anna, Pita, Guillermo, Alonso, M, Wang, Qin, Bolla, Manjeet, Czene, Kamila, Eriksson, Mikael, Humphreys, Keith, Darabi, Hatef, Li, Jingmei, Orr, Nicholas, Schoemaker, Minouk, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Andrulis, Irene, Knight, Julia, Glendon, Gord, Mulligan, Anna, Bojesen, Stig, Nordestgaard, Børge, Flyger, Henrik, Nevanlinna, Heli, Muranen, Taru, Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Wang, Xianshu, Olson, Janet, Vachon, Celine, Purrington, Kristen, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Dunning, Alison, Shah, Mitul, Guénel, Pascal, Truong, Thérèse, Sanchez, Marie, Mulot, Claire, Brenner, Hermann, Dieffenbach, Aida, Arndt, Volker, Stegmaier, Christa, Lindblom, Annika, Margolin, Sara, Hooning, Maartje, Hollestelle, Antoinette, Collée, J, Jager, Agnes, Cox, Angela, Brock, Ian, Reed, Malcolm, Devilee, Peter, Tollenaar, Robert, Seynaeve, Caroline, Haiman, Christopher, Henderson, Brian, Schumacher, Fredrick, Le Marchand, Loic, Simard, Jacques, Dumont, Martine, Soucy, Penny, Dörk, Thilo, Bogdanova, Natalia, Hamann, Ute, Försti, Asta, Rüdiger, Thomas, Ulmer, Hans-Ulrich, Fasching, Peter, Häberle, Lothar, Ekici, Arif, Beckmann, Matthias, Fletcher, Olivia, Johnson, Nichola, dos Santos Silva, Isabel, Peto, Julian, Radice, Paolo, Peterlongo, Paolo, Peissel, Bernard, Mariani, Paolo, Giles, Graham, Severi, Gianluca, Baglietto, Laura, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, and Miller, Nicola

Subjects
Breast Neoplasms, Case-Control Studies, Epistasis, Genetic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Logistic Models, Polymorphism, Single Nucleotide
Abstract

Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10(-4)) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10(-8). Results from the second analytic approach were consistent with those from the first (P > 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.

Published
2014

4. A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46 450 cases and 42 461 controls from the breast cancer association consortium

Author

Milne, Roger L, Herranz, Jesús, Michailidou, Kyriaki, Dennis, Joe, Tyrer, Jonathan P, Zamora, M Pilar, Arias-Perez, José Ignacio, González-Neira, Anna, Pita, Guillermo, Alonso, M Rosario, Wang, Qin, Bolla, Manjeet K, Czene, Kamila, Eriksson, Mikael, Humphreys, Keith, Darabi, Hatef, Li, Jingmei, Anton-Culver, Hoda, Neuhausen, Susan L, Ziogas, Argyrios, Clarke, Christina A, Hopper, John L, Dite, Gillian S, Apicella, Carmel, Southey, Melissa C, Chenevix-Trench, Georgia, Swerdlow, Anthony, Ashworth, Alan, Orr, Nicholas, Schoemaker, Minouk, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Andrulis, Irene L, Knight, Julia A, Glendon, Gord, Mulligan, Anna Marie, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Nevanlinna, Heli, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Wang, Xianshu, Olson, Janet E, Vachon, Celine, Purrington, Kristen, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Dunning, Alison M, Shah, Mitul, Guénel, Pascal, Truong, Thérèse, Sanchez, Marie, Mulot, Claire, Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Stegmaier, Christa, Lindblom, Annika, Margolin, Sara, Hooning, Maartje J, Hollestelle, Antoinette, Collée, J Margriet, Jager, Agnes, Cox, Angela, Brock, Ian W, Reed, Malcolm WR, Devilee, Peter, Tollenaar, Robert AEM, Seynaeve, Caroline, Haiman, Christopher A, Henderson, Brian E, Schumacher, Fredrick, Le Marchand, Loic, Simard, Jacques, Dumont, Martine, Soucy, Penny, Dörk, Thilo, Bogdanova, Natalia V, Hamann, Ute, Försti, Asta, Rüdiger, Thomas, Ulmer, Hans-Ulrich, Fasching, Peter A, Häberle, Lothar, Ekici, Arif B, Beckmann, Matthias W, Fletcher, Olivia, Johnson, Nichola, dos Santos Silva, Isabel, and Peto, Julian

Subjects
Breast Cancer, Human Genome, Genetics, Cancer, Prevention, 2.1 Biological and endogenous factors, Aetiology, Breast Neoplasms, Case-Control Studies, Epistasis, Genetic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Logistic Models, Polymorphism, Single Nucleotide, kConFab Investigators, Australian Ovarian Cancer Study Group, GENICA Network, TNBCC, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10(-4)) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10(-8). Results from the second analytic approach were consistent with those from the first (P > 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.

Published
2014

5. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Author

Lu, Yi, Cuellar-Partida, Gabriel, Painter, Jodie N., Nyholt, Dale R., Morris, Andrew P., Fasching, Peter A., Hein, Alexander, Burghaus, Stefanie, Beckmann, Matthias W., Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Vanderstichele, Adriaan, Doherty, Jennifer Anne, Rossing, Mary Anne, Wicklund, Kristine G., Chang-Claude, Jenny, Eilber, Ursula, Rudolph, Anja, Wang-Gohrke, Shan, Goodman, Marc T., Bogdanova, Natalia, Dörk, Thilo, Dürst, Matthias, Hillemanns, Peter, Runnebaum, Ingo B., Antonenkova, Natalia, Butzow, Ralf, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M., Edwards, Robert P., Kelley, Joseph L., Modugno, Francesmary, Moysich, Kirsten B., Ness, Roberta B., Cannioto, Rikki, Høgdall, Estrid, Jensen, Allan, Giles, Graham G., Bruinsma, Fiona, Kjaer, Susanne K., Hildebrandt, Michelle A.T., Liang, Dong, Lu, Karen H., Wu, Xifeng, Bisogna, Maria, Dao, Fanny, Levine, Douglas A., Cramer, Daniel W., Terry, Kathryn L., Tworoger, Shelley S., Missmer, Stacey, Bjorge, Line, Salvesen, Helga B., Kopperud, Reidun K., Bischof, Katharina, Aben, Katja K.H., Kiemeney, Lambertus A., Massuger, Leon F.A.G., Brooks-Wilson, Angela, Olson, Sara H., McGuire, Valerie, Rothstein, Joseph H., Sieh, Weiva, Whittemore, Alice S., Cook, Linda S., Le, Nhu D., Gilks, C. Blake, Gronwald, Jacek, Jakubowska, Anna, Lubiński, Jan, Gawełko, Jan, Song, Honglin, Tyrer, Jonathan P., Wentzensen, Nicolas, Brinton, Louise, Trabert, Britton, Lissowska, Jolanta, Mclaughlin, John R., Narod, Steven A., Phelan, Catherine, Anton-Culver, Hoda, Ziogas, Argyrios, Eccles, Diana, Gayther, Simon A., Gentry-Maharaj, Aleksandra, Menon, Usha, Ramus, Susan J., Wu, Anna H., Dansonka-Mieszkowska, Agnieszka, Kupryjanczyk, Jolanta, Timorek, Agnieszka, Szafron, Lukasz, Cunningham, Julie M., Fridley, Brooke L., Winham, Stacey J., Bandera, Elisa V., Poole, Elizabeth M., Morgan, Terry K., Risch, Harvey A., Goode, Ellen L., Schildkraut, Joellen M., Webb, Penelope M., Pearce, Celeste L., Berchuck, Andrew, Pharoah, Paul D.P., Montgomery, Grant W., Zondervan, Krina T., Chenevix-Trench, Georgia, MacGregor, Stuart, Anderson, Carl A., Gordon, Scott D., Guo, Qun, Henders, Anjali K., Lambert, Ann, Lee, Sang Hong, Kraft, Peter, Kennedy, Stephen H., Macgregor, Stuart, Martin, Nicholas G., Missmer, Stacey A., Montgomery, Grant W., Morris, Andrew P., Nyholt, Dale R., Painter, Jodie N., Roseman, Fenella, Treloar, Susan A., Visscher, Peter M., Wallace, Leanne, and Zondervan, Krina T.

Published
2015
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7. A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

Author

Pooley, Karen A., Bojesen, Stig E., Weischer, Maren, Nielsen, Sune F., Thompson, Deborah, Amin Al Olama, Ali, Michailidou, Kyriaki, Tyrer, Jonathan P., Benlloch, Sara, Brown, Judith, Audley, Tina, Luben, Robert, Khaw, K-T, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Kote-Jarai, Zsofia, Baynes, Caroline, Shah, Mitul, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Dicks, Ed, Yang, Rongxi, Rudolph, Anja, Schildkraut, Joellen, Chang-Claude, Jenny, Burwinkel, Barbara, Chenevix-Trench, Georgia, Pharoah, Paul D. P., Berchuck, Andrew, Eeles, Rosalind A., Easton, Douglas F., Dunning, Alison M., and Nordestgaard, Børge G.

Published
2013
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