47 results on '"Shen, Howard"'
Search Results
2. Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus
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Buckley, Melissa A, Woods, Nicholas T, Tyrer, Jonathan P, Mendoza-Fandiño, Gustavo, Lawrenson, Kate, Hazelett, Dennis J, Najafabadi, Hamed S, Gjyshi, Anxhela, Carvalho, Renato S, Lyra, Paulo C, Coetzee, Simon G, Shen, Howard C, Yang, Ally W, Earp, Madalene A, Yoder, Sean J, Risch, Harvey, Chenevix-Trench, Georgia, Ramus, Susan J, Phelan, Catherine M, Coetzee, Gerhard A, Noushmehr, Houtan, Hughes, Timothy R, Sellers, Thomas A, Goode, Ellen L, Pharoah, Paul D, Gayther, Simon A, and Monteiro, Alvaro NA
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Prevention ,Human Genome ,Cancer ,Rare Diseases ,Biotechnology ,Ovarian Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Base Sequence ,Carcinoma ,Ovarian Epithelial ,Cell Cycle Proteins ,Cell Line ,Tumor ,Chromosome Mapping ,Chromosomes ,Human ,Pair 9 ,Cystadenocarcinoma ,Serous ,DNA ,Neoplasm ,DNA-Binding Proteins ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,HEK293 Cells ,Humans ,Linkage Disequilibrium ,Ovarian Neoplasms ,Polymorphism ,Single Nucleotide ,Ovarian Cancer Association Consortium ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. SIGNIFICANCE: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene.See related commentary by Choi and Brown, p. 439.
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- 2019
3. Amyloid conformation-dependent disaggregation in a reconstituted yeast prion system
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Nakagawa, Yoshiko, Shen, Howard C.-H., Komi, Yusuke, Sugiyama, Shinju, Kurinomaru, Takaaki, Tomabechi, Yuri, Krayukhina, Elena, Okamoto, Kenji, Yokoyama, Takeshi, Shirouzu, Mikako, Uchiyama, Susumu, Inaba, Megumi, Niwa, Tatsuya, Sako, Yasushi, Taguchi, Hideki, and Tanaka, Motomasa
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- 2022
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4. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci
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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
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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.
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- 2015
5. Identification of six new susceptibility loci for invasive epithelial ovarian cancer.
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Kuchenbaecker, Karoline B, Ramus, Susan J, Tyrer, Jonathan, Lee, Andrew, Shen, Howard C, Beesley, Jonathan, Lawrenson, Kate, McGuffog, Lesley, Healey, Sue, Lee, Janet M, Spindler, Tassja J, Lin, Yvonne G, Pejovic, Tanja, Bean, Yukie, Li, Qiyuan, Coetzee, Simon, Hazelett, Dennis, Miron, Alexander, Southey, Melissa, Terry, Mary Beth, Goldgar, David E, Buys, Saundra S, Janavicius, Ramunas, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Neuhausen, Susan L, Ding, Yuan Chun, Hansen, Thomas VO, Jønson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, Barrowdale, Daniel, Dennis, Joe, Benitez, Javier, Osorio, Ana, Garcia, Maria Jose, Komenaka, Ian, Weitzel, Jeffrey N, Ganschow, Pamela, Peterlongo, Paolo, Bernard, Loris, Viel, Alessandra, Bonanni, Bernardo, Peissel, Bernard, Manoukian, Siranoush, Radice, Paolo, Papi, Laura, Ottini, Laura, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Frost, Debra, Perkins, Jo, Platte, Radka, Ellis, Steve, EMBRACE, Godwin, Andrew K, Schmutzler, Rita Katharina, Meindl, Alfons, Engel, Christoph, Sutter, Christian, Sinilnikova, Olga M, GEMO Study Collaborators, Damiola, Francesca, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Claes, Kathleen, De Leeneer, Kim, Kirk, Judy, Rodriguez, Gustavo C, Piedmonte, Marion, O'Malley, David M, de la Hoya, Miguel, Caldes, Trinidad, Aittomäki, Kristiina, Nevanlinna, Heli, Collée, J Margriet, Rookus, Matti A, Oosterwijk, Jan C, Breast Cancer Family Registry, Tihomirova, Laima, Tung, Nadine, Hamann, Ute, Isaccs, Claudine, Tischkowitz, Marc, Imyanitov, Evgeny N, Caligo, Maria A, Campbell, Ian G, Hogervorst, Frans BL, HEBON, Olah, Edith, Diez, Orland, Blanco, Ignacio, Brunet, Joan, Lazaro, Conxi, Pujana, Miquel Angel, Jakubowska, Anna, Gronwald, Jacek, Lubinski, Jan, and Sukiennicki, Grzegorz
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EMBRACE ,GEMO Study Collaborators ,Breast Cancer Family Registry ,HEBON ,KConFab Investigators ,Australian Cancer Study ,Australian Ovarian Cancer Study Group ,Consortium of Investigators of Modifiers of BRCA1 and BRCA2 ,Humans ,Neoplasms ,Glandular and Epithelial ,Ovarian Neoplasms ,Genetic Predisposition to Disease ,BRCA1 Protein ,BRCA2 Protein ,Risk ,Genotype ,Heterozygote ,Mutation ,Polymorphism ,Single Nucleotide ,Alleles ,Genes ,Reporter ,Quantitative Trait Loci ,Adolescent ,Adult ,Female ,Genome-Wide Association Study ,Young Adult ,Carcinoma ,Ovarian Epithelial ,Human Genome ,Rare Diseases ,Genetics ,Cancer ,Prevention ,Ovarian Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
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- 2015
6. Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome
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Charbonneau, Bridget, Moysich, Kirsten B, Kalli, Kimberly R, Oberg, Ann L, Vierkant, Robert A, Fogarty, Zachary C, Block, Matthew S, Maurer, Matthew J, Goergen, Krista M, Fridley, Brooke L, Cunningham, Julie M, Rider, David N, Preston, Claudia, Hartmann, Lynn C, Lawrenson, Kate, Wang, Chen, Tyrer, Jonathan, Song, Honglin, deFazio, Anna, Johnatty, Sharon E, Doherty, Jennifer A, Phelan, Catherine M, Sellers, Thomas A, Ramirez, Starr M, Vitonis, Allison F, Terry, Kathryn L, Van Den Berg, David, Pike, Malcolm C, Wu, Anna H, Berchuck, Andrew, Gentry-Maharaj, Aleksandra, Ramus, Susan J, Diergaarde, Brenda, Shen, Howard, Jensen, Allan, Menkiszak, Janusz, Cybulski, Cezary, Lubiński, Jan, Ziogas, Argyrios, Rothstein, Joseph H, McGuire, Valerie, Sieh, Weiva, Lester, Jenny, Walsh, Christine, Vergote, Ignace, Lambrechts, Sandrina, Despierre, Evelyn, Garcia-Closas, Montserrat, Yang, Hannah, Brinton, Louise A, Spiewankiewicz, Beata, Rzepecka, Iwona K, Dansonka-Mieszkowska, Agnieszka, Seibold, Petra, Rudolph, Anja, Paddock, Lisa E, Orlow, Irene, Lundvall, Lene, Olson, Sara H, Hogdall, Claus K, Schwaab, Ira, du Bois, Andreas, Harter, Philipp, Flanagan, James M, Brown, Robert, Paul, James, Ekici, Arif B, Beckmann, Matthias W, Hein, Alexander, Eccles, Diana, Lurie, Galina, Hays, Laura E, Bean, Yukie T, Pejovic, Tanja, Goodman, Marc T, Campbell, Ian, Fasching, Peter A, Konecny, Gottfried, Kaye, Stanley B, Heitz, Florian, Hogdall, Estrid, Bandera, Elisa V, Chang-Claude, Jenny, Kupryjanczyk, Jolanta, Wentzensen, Nicolas, Lambrechts, Diether, Karlan, Beth Y, Whittemore, Alice S, Culver, Hoda Anton, Gronwald, Jacek, Levine, Douglas A, Kjaer, Susanne K, Menon, Usha, Schildkraut, Joellen M, Pearce, Celeste Leigh, Cramer, Daniel W, Rossing, Mary Anne, Chenevix-Trench, Georgia, group, for the AOCS, and ACS
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Genetics ,Clinical Research ,Ovarian Cancer ,Rare Diseases ,Women's Health ,2.1 Biological and endogenous factors ,Female ,Gene Expression ,Gene Expression Profiling ,Genetic Predisposition to Disease ,Genetic Variation ,Germ-Line Mutation ,Humans ,Interleukin-2 Receptor alpha Subunit ,Neoplasm Grading ,Neoplasm Invasiveness ,Ovarian Neoplasms ,Patient Outcome Assessment ,Polymorphism ,Single Nucleotide ,Prognosis ,T-Lymphocytes ,Regulatory ,AOCS group ,ACS ,Pharmacology and Pharmaceutical Sciences ,Oncology and carcinogenesis - Abstract
The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 × 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 × 10(-5)), rs2476491 (HR, = 1.40; 95% CI, 1.19-1.64; P = 5.6 × 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 × 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 × 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.
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- 2014
7. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.
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Bojesen, Stig E, Pooley, Karen A, Johnatty, Sharon E, Beesley, Jonathan, Michailidou, Kyriaki, Tyrer, Jonathan P, Edwards, Stacey L, Pickett, Hilda A, Shen, Howard C, Smart, Chanel E, Hillman, Kristine M, Mai, Phuong L, Lawrenson, Kate, Stutz, Michael D, Lu, Yi, Karevan, Rod, Woods, Nicholas, Johnston, Rebecca L, French, Juliet D, Chen, Xiaoqing, Weischer, Maren, Nielsen, Sune F, Maranian, Melanie J, Ghoussaini, Maya, Ahmed, Shahana, Baynes, Caroline, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Healey, Sue, Lush, Michael, Tessier, Daniel C, Vincent, Daniel, Bacot, Françis, Australian Cancer Study, Australian Ovarian Cancer Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), Gene Environment Interaction and Breast Cancer (GENICA), Swedish Breast Cancer Study (SWE-BRCA), Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Epidemiological study of BRCA1 & BRCA2 Mutation Carriers (EMBRACE), Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO), Vergote, Ignace, Lambrechts, Sandrina, Despierre, Evelyn, Risch, Harvey A, González-Neira, Anna, Rossing, Mary Anne, Pita, Guillermo, Doherty, Jennifer A, Alvarez, Nuria, Larson, Melissa C, Fridley, Brooke L, Schoof, Nils, Chang-Claude, Jenny, Cicek, Mine S, Peto, Julian, Kalli, Kimberly R, Broeks, Annegien, Armasu, Sebastian M, Schmidt, Marjanka K, Braaf, Linde M, Winterhoff, Boris, Nevanlinna, Heli, Konecny, Gottfried E, Lambrechts, Diether, Rogmann, Lisa, Guénel, Pascal, Teoman, Attila, Milne, Roger L, Garcia, Joaquin J, Cox, Angela, Shridhar, Vijayalakshmi, Burwinkel, Barbara, Marme, Frederik, Hein, Rebecca, Sawyer, Elinor J, Haiman, Christopher A, Wang-Gohrke, Shan, Andrulis, Irene L, Moysich, Kirsten B, Hopper, John L, Odunsi, Kunle, Lindblom, Annika, Giles, Graham G, Brenner, Hermann, Simard, Jacques, Lurie, Galina, Fasching, Peter A, Carney, Michael E, Radice, Paolo, Wilkens, Lynne R, Swerdlow, Anthony, Goodman, Marc T, Brauch, Hiltrud, Garcia-Closas, Montserrat, and Hillemanns, Peter
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Australian Cancer Study ,Australian Ovarian Cancer Study ,Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer ,Gene Environment Interaction and Breast Cancer ,Swedish Breast Cancer Study ,Hereditary Breast and Ovarian Cancer Research Group Netherlands ,Epidemiological study of BRCA1 & BRCA2 Mutation Carriers ,Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers ,Chromatin ,Telomere ,Humans ,Breast Neoplasms ,Ovarian Neoplasms ,Genetic Predisposition to Disease ,Luciferases ,Telomerase ,RNA ,Messenger ,Oligonucleotide Array Sequence Analysis ,Risk Factors ,Case-Control Studies ,Gene Expression Profiling ,Reverse Transcriptase Polymerase Chain Reaction ,DNA Methylation ,Alternative Splicing ,Genotype ,Polymorphism ,Single Nucleotide ,Female ,Genome-Wide Association Study ,Genetic Loci ,Real-Time Polymerase Chain Reaction ,Biomarkers ,Tumor ,Genetics ,Breast Cancer ,Cancer ,Ovarian Cancer ,Rare Diseases ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
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- 2013
8. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.
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Pharoah, Paul DP, Tsai, Ya-Yu, Ramus, Susan J, Phelan, Catherine M, Goode, Ellen L, Lawrenson, Kate, Buckley, Melissa, Fridley, Brooke L, Tyrer, Jonathan P, Shen, Howard, Weber, Rachel, Karevan, Rod, Larson, Melissa C, Song, Honglin, Tessier, Daniel C, Bacot, François, Vincent, Daniel, Cunningham, Julie M, Dennis, Joe, Dicks, Ed, Australian Cancer Study, Australian Ovarian Cancer Study Group, Aben, Katja K, Anton-Culver, Hoda, Antonenkova, Natalia, Armasu, Sebastian M, Baglietto, Laura, Bandera, Elisa V, Beckmann, Matthias W, Birrer, Michael J, Bloom, Greg, Bogdanova, Natalia, Brenton, James D, Brinton, Louise A, Brooks-Wilson, Angela, Brown, Robert, Butzow, Ralf, Campbell, Ian, Carney, Michael E, Carvalho, Renato S, Chang-Claude, Jenny, Chen, Y Anne, Chen, Zhihua, Chow, Wong-Ho, Cicek, Mine S, Coetzee, Gerhard, Cook, Linda S, Cramer, Daniel W, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Edwards, Robert, Ekici, Arif B, Fasching, Peter A, Fenstermacher, David, Flanagan, James, Gao, Yu-Tang, Garcia-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Giles, Graham, Gjyshi, Anxhela, Gore, Martin, Gronwald, Jacek, Guo, Qi, Halle, Mari K, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hillemanns, Peter, Hoatlin, Maureen, Høgdall, Estrid, Høgdall, Claus K, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Kalli, Kimberly R, Karlan, Beth Y, Kelemen, Linda E, Kiemeney, Lambertus A, Kjaer, Susanne Krüger, Konecny, Gottfried E, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Nathan, Lee, Janet, Leminen, Arto, Lim, Boon Kiong, Lissowska, Jolanta, Lubiński, Jan, Lundvall, Lene, Lurie, Galina, and Massuger, Leon FAG
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Australian Cancer Study ,Australian Ovarian Cancer Study Group ,Humans ,Cystadenocarcinoma ,Serous ,Ovarian Neoplasms ,Neoplasm Invasiveness ,Genetic Predisposition to Disease ,Risk Factors ,Case-Control Studies ,Cooperative Behavior ,Genotype ,Polymorphism ,Single Nucleotide ,Female ,Meta-Analysis as Topic ,Genome-Wide Association Study ,Genetic Loci ,Gene-Environment Interaction ,Cancer ,Human Genome ,Prevention ,Genetics ,Rare Diseases ,Ovarian Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
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- 2013
9. Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
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Permuth-Wey, Jennifer, Lawrenson, Kate, Shen, Howard C, Velkova, Aneliya, Tyrer, Jonathan P, Chen, Zhihua, Lin, Hui-Yi, Ann Chen, Y, Tsai, Ya-Yu, Qu, Xiaotao, Ramus, Susan J, Karevan, Rod, Lee, Janet, Lee, Nathan, Larson, Melissa C, Aben, Katja K, Anton-Culver, Hoda, Antonenkova, Natalia, Antoniou, Antonis C, Armasu, Sebastian M, Bacot, François, Baglietto, Laura, Bandera, Elisa V, Barnholtz-Sloan, Jill, Beckmann, Matthias W, Birrer, Michael J, Bloom, Greg, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Brown, Robert, Butzow, Ralf, Cai, Qiuyin, Campbell, Ian, Chang-Claude, Jenny, Chanock, Stephen, Chenevix-Trench, Georgia, Cheng, Jin Q, Cicek, Mine S, Coetzee, Gerhard A, Cook, Linda S, Couch, Fergus J, Cramer, Daniel W, Cunningham, Julie M, Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Easton, Douglas F, Eccles, Diana, Edwards, Robert, Ekici, Arif B, Fasching, Peter A, Fenstermacher, David A, Flanagan, James M, Garcia-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind M, Gonzalez-Bosquet, Jesus, Goodman, Marc T, Gore, Martin, Górski, Bohdan, Gronwald, Jacek, Hall, Per, Halle, Mari K, Harter, Philipp, Heitz, Florian, Hillemanns, Peter, Hoatlin, Maureen, Høgdall, Claus K, Høgdall, Estrid, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Jim, Heather, Kalli, Kimberly R, Karlan, Beth Y, Kaye, Stanley B, Kelemen, Linda E, Kiemeney, Lambertus A, Kikkawa, Fumitaka, Konecny, Gottfried E, Krakstad, Camilla, Krüger Kjaer, Susanne, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Lancaster, Johnathan M, Le, Nhu D, Leminen, Arto, Levine, Douglas A, Liang, Dong, Kiong Lim, Boon, Lin, Jie, Lissowska, Jolanta, Lu, Karen H, and Lubiński, Jan
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Rare Diseases ,Biotechnology ,Ovarian Cancer ,Cancer ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Carcinoma ,Ovarian Epithelial ,Chromosomes ,Human ,Pair 17 ,Female ,Genetic Predisposition to Disease ,Humans ,Neoplasms ,Glandular and Epithelial ,Ovarian Neoplasms ,Polymorphism ,Single Nucleotide ,Australian Cancer Study ,Australian Ovarian Cancer Study ,Consortium of Investigators of Modifiers of BRCA1/2 - Abstract
Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.
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- 2013
10. Segments in the Amyloid Core that Distinguish Hamster from Mouse Prion Fibrils
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Shen, Howard C.-H., Chen, Yung-Han, Lin, Yu-Sheng, Chu, Brett K.-Y., Liang, Ching-Shin, Yang, Chien-Chih, and Chen, Rita P.-Y.
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- 2019
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11. Data from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome
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Charbonneau, Bridget, primary, Moysich, Kirsten B., primary, Kalli, Kimberly R., primary, Oberg, Ann L., primary, Vierkant, Robert A., primary, Fogarty, Zachary C., primary, Block, Matthew S., primary, Maurer, Matthew J., primary, Goergen, Krista M., primary, Fridley, Brooke L., primary, Cunningham, Julie M., primary, Rider, David N., primary, Preston, Claudia, primary, Hartmann, Lynn C., primary, Lawrenson, Kate, primary, Wang, Chen, primary, Tyrer, Jonathan, primary, Song, Honglin, primary, deFazio, Anna, primary, Johnatty, Sharon E., primary, Doherty, Jennifer A., primary, Phelan, Catherine M., primary, Sellers, Thomas A., primary, Ramirez, Starr M., primary, Vitonis, Allison F., primary, Terry, Kathryn L., primary, Van Den Berg, David, primary, Pike, Malcolm C., primary, Wu, Anna H., primary, Berchuck, Andrew, primary, Gentry-Maharaj, Aleksandra, primary, Ramus, Susan J., primary, Diergaarde, Brenda, primary, Shen, Howard, primary, Jensen, Allan, primary, Menkiszak, Janusz, primary, Cybulski, Cezary, primary, Lubiński, Jan, primary, Ziogas, Argyrios, primary, Rothstein, Joseph H., primary, McGuire, Valerie, primary, Sieh, Weiva, primary, Lester, Jenny, primary, Walsh, Christine, primary, Vergote, Ignace, primary, Lambrechts, Sandrina, primary, Despierre, Evelyn, primary, Garcia-Closas, Montserrat, primary, Yang, Hannah, primary, Brinton, Louise A., primary, Spiewankiewicz, Beata, primary, Rzepecka, Iwona K., primary, Dansonka-Mieszkowska, Agnieszka, primary, Seibold, Petra, primary, Rudolph, Anja, primary, Paddock, Lisa E., primary, Orlow, Irene, primary, Lundvall, Lene, primary, Olson, Sara H., primary, Hogdall, Claus K., primary, Schwaab, Ira, primary, du Bois, Andreas, primary, Harter, Philipp, primary, Flanagan, James M., primary, Brown, Robert, primary, Paul, James, primary, Ekici, Arif B., primary, Beckmann, Matthias W., primary, Hein, Alexander, primary, Eccles, Diana, primary, Lurie, Galina, primary, Hays, Laura E., primary, Bean, Yukie T., primary, Pejovic, Tanja, primary, Goodman, Marc T., primary, Campbell, Ian, primary, Fasching, Peter A., primary, Konecny, Gottfried, primary, Kaye, Stanley B., primary, Heitz, Florian, primary, Hogdall, Estrid, primary, Bandera, Elisa V., primary, Chang-Claude, Jenny, primary, Kupryjanczyk, Jolanta, primary, Wentzensen, Nicolas, primary, Lambrechts, Diether, primary, Karlan, Beth Y., primary, Whittemore, Alice S., primary, Culver, Hoda Anton, primary, Gronwald, Jacek, primary, Levine, Douglas A., primary, Kjaer, Susanne K., primary, Menon, Usha, primary, Schildkraut, Joellen M., primary, Pearce, Celeste Leigh, primary, Cramer, Daniel W., primary, Rossing, Mary Anne, primary, Chenevix-Trench, Georgia, primary, Pharoah, Paul D.P., primary, Gayther, Simon A., primary, Ness, Roberta B., primary, Odunsi, Kunle, primary, Sucheston, Lara E., primary, Knutson, Keith L., primary, and Goode, Ellen L., primary
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- 2023
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12. Supplementary Tables 1 - 4 from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome
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Charbonneau, Bridget, primary, Moysich, Kirsten B., primary, Kalli, Kimberly R., primary, Oberg, Ann L., primary, Vierkant, Robert A., primary, Fogarty, Zachary C., primary, Block, Matthew S., primary, Maurer, Matthew J., primary, Goergen, Krista M., primary, Fridley, Brooke L., primary, Cunningham, Julie M., primary, Rider, David N., primary, Preston, Claudia, primary, Hartmann, Lynn C., primary, Lawrenson, Kate, primary, Wang, Chen, primary, Tyrer, Jonathan, primary, Song, Honglin, primary, deFazio, Anna, primary, Johnatty, Sharon E., primary, Doherty, Jennifer A., primary, Phelan, Catherine M., primary, Sellers, Thomas A., primary, Ramirez, Starr M., primary, Vitonis, Allison F., primary, Terry, Kathryn L., primary, Van Den Berg, David, primary, Pike, Malcolm C., primary, Wu, Anna H., primary, Berchuck, Andrew, primary, Gentry-Maharaj, Aleksandra, primary, Ramus, Susan J., primary, Diergaarde, Brenda, primary, Shen, Howard, primary, Jensen, Allan, primary, Menkiszak, Janusz, primary, Cybulski, Cezary, primary, Lubiński, Jan, primary, Ziogas, Argyrios, primary, Rothstein, Joseph H., primary, McGuire, Valerie, primary, Sieh, Weiva, primary, Lester, Jenny, primary, Walsh, Christine, primary, Vergote, Ignace, primary, Lambrechts, Sandrina, primary, Despierre, Evelyn, primary, Garcia-Closas, Montserrat, primary, Yang, Hannah, primary, Brinton, Louise A., primary, Spiewankiewicz, Beata, primary, Rzepecka, Iwona K., primary, Dansonka-Mieszkowska, Agnieszka, primary, Seibold, Petra, primary, Rudolph, Anja, primary, Paddock, Lisa E., primary, Orlow, Irene, primary, Lundvall, Lene, primary, Olson, Sara H., primary, Hogdall, Claus K., primary, Schwaab, Ira, primary, du Bois, Andreas, primary, Harter, Philipp, primary, Flanagan, James M., primary, Brown, Robert, primary, Paul, James, primary, Ekici, Arif B., primary, Beckmann, Matthias W., primary, Hein, Alexander, primary, Eccles, Diana, primary, Lurie, Galina, primary, Hays, Laura E., primary, Bean, Yukie T., primary, Pejovic, Tanja, primary, Goodman, Marc T., primary, Campbell, Ian, primary, Fasching, Peter A., primary, Konecny, Gottfried, primary, Kaye, Stanley B., primary, Heitz, Florian, primary, Hogdall, Estrid, primary, Bandera, Elisa V., primary, Chang-Claude, Jenny, primary, Kupryjanczyk, Jolanta, primary, Wentzensen, Nicolas, primary, Lambrechts, Diether, primary, Karlan, Beth Y., primary, Whittemore, Alice S., primary, Culver, Hoda Anton, primary, Gronwald, Jacek, primary, Levine, Douglas A., primary, Kjaer, Susanne K., primary, Menon, Usha, primary, Schildkraut, Joellen M., primary, Pearce, Celeste Leigh, primary, Cramer, Daniel W., primary, Rossing, Mary Anne, primary, Chenevix-Trench, Georgia, primary, Pharoah, Paul D.P., primary, Gayther, Simon A., primary, Ness, Roberta B., primary, Odunsi, Kunle, primary, Sucheston, Lara E., primary, Knutson, Keith L., primary, and Goode, Ellen L., primary
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- 2023
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13. Supplementary Table 5 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
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Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary
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- 2023
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14. Supplementary Figures 1-4 and extended methods from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
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Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary
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- 2023
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15. Supplementary Table 3 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
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Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary
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- 2023
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16. Data from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
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Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary
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- 2023
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17. Supplementary Table 1 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
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Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary
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- 2023
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18. Supplementary Table 2 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
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Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary
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- 2023
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19. Supplementary Table 4 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
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Buckley, Melissa A., primary, Woods, Nicholas T., primary, Tyrer, Jonathan P., primary, Mendoza-Fandiño, Gustavo, primary, Lawrenson, Kate, primary, Hazelett, Dennis J., primary, Najafabadi, Hamed S., primary, Gjyshi, Anxhela, primary, Carvalho, Renato S., primary, Lyra, Paulo C., primary, Coetzee, Simon G., primary, Shen, Howard C., primary, Yang, Ally W., primary, Earp, Madalene A., primary, Yoder, Sean J., primary, Risch, Harvey, primary, Chenevix-Trench, Georgia, primary, Ramus, Susan J., primary, Phelan, Catherine M., primary, Coetzee, Gerhard A., primary, Noushmehr, Houtan, primary, Hughes, Timothy R., primary, Sellers, Thomas A., primary, Goode, Ellen L., primary, Pharoah, Paul D., primary, Gayther, Simon A., primary, and Monteiro, Alvaro N.A., primary
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- 2023
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20. An intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice
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Cheng, Yu‐Sung, Chen, Zih‐ten, Liao, Tai‐Yan, Lin, Chen, Shen, Howard C‐H, Wang, Ya‐Han, Chang, Chi‐Wei, Liu, Ren‐Shyan, Chen, Rita P‐Y, and Tu, Pang‐hsien
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- 2017
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21. Androgen Receptor Antagonists
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Shen, Howard C., Taplin, Mary-Ellen, Balk, Steven P., Figg, William D., editor, Chau, Cindy H., editor, and Small, Eric J., editor
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- 2010
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22. Development of Androgen Receptor Antagonists with Promising Activity in Castration-Resistant Prostate Cancer
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Shen, Howard C. and Balk, Steven P.
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- 2009
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23. Amyloid conformation-dependent disaggregation revealed by a reconstituted yeast prion system
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Tanaka, Motomasa, primary, Nakagawa, Yoshiko, additional, Shen, Howard C.-H., additional, Sugiyama, Shinju, additional, Tomabechi, Yuri, additional, Krayukhina, Elena, additional, Okamoto, Kenji, additional, Yokoyama, Takeshi, additional, Shirouzu, Mikako, additional, Uchiyama, Susumu, additional, Inaba, Megumi, additional, Niwa, Tatsuya, additional, Sako, Yasushi, additional, and Taguchi, Hideki, additional
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- 2020
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24. In Silico Discovery of Androgen Receptor Antagonists with Activity in Castration Resistant Prostate Cancer
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Shen, Howard C., Shanmugasundaram, Kumaran, Simon, Nicholas I., Cai, Changmeng, Wang, Hongyun, Chen, Sen, Balk, Steven P., and Rigby, Alan C.
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- 2012
25. The Androgen Receptor: Unlocking the Secrets of Its Unique Transactivation Domain
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Shen, Howard C., primary and Coetzee, Gerhard A., additional
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- 2005
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26. Androgen Receptor-Mediated Repression of Novel Target Genes
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Prescott, Jennifer, Jariwala, Unnati, Jia, Li, Cogan, Jon P., Barski, Artem, Pregizer, Steve, Shen, Howard C., Arasheben, Armin, Neilson, Jessica J., Frenkel, Baruch, and Coetzee, Gerhard A.
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- 2007
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27. Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
- Author
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Buckley, Melissa A, Woods, Nicholas T, Tyrer, Jonathan P, Mendoza-Fandiño, Gustavo, Lawrenson, Kate, Hazelett, Dennis J, Najafabadi, Hamed S, Gjyshi, Anxhela, Carvalho, Renato S, Lyra, Paulo C, Coetzee, Simon G, Shen, Howard C, Yang, Ally W, Earp, Madalene A, Yoder, Sean J, Risch, Harvey, Chenevix-Trench, Georgia, Ramus, Susan J, Phelan, Catherine M, Coetzee, Gerhard A, Noushmehr, Houtan, Hughes, Timothy R, Sellers, Thomas A, Goode, Ellen L, Pharoah, Paul D, Gayther, Simon A, Monteiro, Alvaro NA, Ovarian Cancer Association Consortium, Lawrenson, Kate [0000-0002-6469-2515], Hazelett, Dennis J [0000-0003-0749-9935], Najafabadi, Hamed S [0000-0003-2735-4231], Coetzee, Simon G [0000-0003-4267-5930], Yoder, Sean J [0000-0003-0005-7798], Coetzee, Gerhard A [0000-0003-4267-5930], Noushmehr, Houtan [0000-0003-4051-8114], and Apollo - University of Cambridge Repository
- Subjects
Ovarian Cancer Association Consortium ,Oncology and Carcinogenesis ,Cystadenocarcinoma ,Cell Cycle Proteins ,Carcinoma, Ovarian Epithelial ,Polymorphism, Single Nucleotide ,Chromosomes ,Linkage Disequilibrium ,Cell Line ,Rare Diseases ,Ovarian Epithelial ,Cell Line, Tumor ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Genetic Predisposition to Disease ,Oncology & Carcinogenesis ,Polymorphism ,Aetiology ,Cancer ,Ovarian Neoplasms ,Tumor ,Base Sequence ,Prevention ,Carcinoma ,Human Genome ,Serous ,Chromosome Mapping ,DNA ,Single Nucleotide ,DNA, Neoplasm ,Ovarian Cancer ,Cystadenocarcinoma, Serous ,DNA-Binding Proteins ,HEK293 Cells ,Neoplasm ,Female ,Chromosomes, Human, Pair 9 ,Human ,Pair 9 ,Biotechnology ,Genome-Wide Association Study - Abstract
Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. SIGNIFICANCE: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene.See related commentary by Choi and Brown, p. 439.
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- 2018
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28. GRIP1 mediates the interaction between the amino- and carboxyl-termini of the androgen receptor
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Shen, Howard C., Buchanan, Grant, Butler, Lisa M., Prescott, Jennifer, Henderson, Michael, Tilley, Wayne D., and Coetzee, Gerhard A.
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- 2005
29. Alzheimer’s and Parkinson’s disease: Brain levels of glutathione, glutathione disulfide, and vitamin E
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Adams, James D., Klaidman, Lori K., Odunze, Ifeoma N., Shen, Howard C., and Miller, Carol A.
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- 1991
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30. Simplifying aerospace part tooling
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Welson, Darren and Shen, Howard
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Starfire Systems Inc. -- Production management ,Ceramic industry -- Production management ,Business ,Engineering and manufacturing industries ,Metals, metalworking and machinery industries - Abstract
Starfire Systems Inc., headquartered in Schenectady, New York, is combining the material advantages of polymers and ceramics with its patented Polymer-to-Ceramic technology. The advanced materials company developed this technology to [...]
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- 2011
31. CD5 Expression Is Developmentally Regulated By T Cell Receptor (TCR) Signals and TCR Avidity
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Azzam, Hala S., Grinberg, Alex, Lui, Kin, Shen, Howard, Shores, Elizabeth W., and Love, Paul E.
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- 1998
32. Role of the Multiple T Cell Receptor (TCR)-ζ Chain Signaling Motifs in Selection of the T Cell Repertoire
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Shores, Elizabeth W., Tran, Tom, Grinberg, Alexander, Sommers, Connie L., Shen, Howard, and Love, Paul E.
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- 1997
33. Abstract PR15: MYC distal enhancers underlie ovarian cancer susceptibility in the 8q24.21 locus.
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Gjyshi, Anxhela, primary, Mendoza-Fandino, Gustavo, additional, Woods, Nicholas, additional, Tyrer, Jonathan, additional, Lawrenson, Kate, additional, Buckley, Melissa, additional, Shen, Howard, additional, Carvalho, Renato, additional, Seo, Ji-Heui, additional, Phelan, Catherine, additional, Freedman, Matthew, additional, Goode, Ellen, additional, Sellers, Thomas, additional, Gayther, Simon, additional, Pharoah, Paul, additional, and Monteiro, Alvaro, additional
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- 2016
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34. Identification of six new susceptibility loci for invasive epithelial ovarian cancer
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Kuchenbaecker, Karoline B., Ramus, Susan J., Tyrer, Jonathan, Lee, Andrew, Shen, Howard C., Beesley, Jonathan, Lawrenson, Kate, McGuffog, Lesley, Healey, Sue, Lee, Janet M., Spindler, Tassja J., Lin, Yvonne G., Pejovic, Tanja, Bean, Yukie, Li, Qiyuan, Coetzee, Simon, Hazelett, Dennis, Miron, Alexander, Southey, Melissa, Terry, Mary Beth, Goldgar, David E., Buys, Saundra S., Janavicius, Ramunas, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Neuhausen, Susan L., Ding, Yuan Chun, Hansen, Thomas V. O., Jonson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, Barrowdale, Daniel, Dennis, Joe, Benitez, Javier, Osorio, Ana, Garcia, Maria Jose, Komenaka, Ian, Weitzel, Jeffrey N., Ganschow, Pamela, Peterlongo, Paolo, Bernard, Loris, Viel, Alessandra, Bonanni, Bernardo, Peissel, Bernard, Manoukian, Siranoush, Radice, Paolo, Papi, Laura, Ottini, Laura, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Frost, Debra, Perkins, Jo, Platte, Radka, Ellis, Steve, Godwin, Andrew K., Schmutzler, Rita Katharina, Meindl, Alfons, Engel, Christoph, Sutter, Christian, Sinilnikova, Olga M., Damiola, Francesca, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Claes, Kathleen, De Leeneer, Kim, Kirk, Judy, Rodriguez, Gustavo C., Piedmonte, Marion, O'Malley, David M., de la Hoya, Miguel, Caldes, Trinidad, Aittomaeki, Kristiina, Nevanlinna, Heli, Collee, J. Margriet, Rookus, Matti A., Oosterwijk, Jan C., Tihomirova, Laima, Tung, Nadine, Hamann, Ute, Isaccs, Claudine, Tischkowitz, Marc, Imyanitov, Evgeny N., Caligo, Maria A., Campbell, Ian G., Hogervorst, Frans B. L., Olah, Edith, Diez, Orland, Blanco, Ignacio, Brunet, Joan, Lazaroso, Conxi, Angel Pujana, Miguel, Jakubowska, Anna, Gronwald, Jacek, Lubinski, Jan, Sukiennicki, Grzegorz, Barkardottir, Rosa B., Plante, Marie, Simard, Jacques, Soucy, Penny, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R., Pankratz, Vernon S., Wang, Xianshu, Lindor, Noralane, Szabo, Csilla I., Kauff, Noah, Vijai, Joseph, Aghajanian, Carol A., Pfeiler, Georg, Berger, Andreas, Singer, Christian F., Tea, Muy-Kheng, Phelan, Catherine M., Greene, Mark H., Mai, Phuong L., Rennert, Gad, Mulligan, Anna Marie, Tchatchou, Sandrine, Andrulis, Irene L., Glendon, Gord, Toland, Amanda Ewart, Jensen, Uffe Birk, Kruse, Torben A., Thomassen, Mads, Bojesen, Anders, Zidan, Jamal, Friedman, Eitan, Laitman, Yael, Soller, Maria, Liljegren, Annelie, Arver, Brita, Einbeigi, Zakaria, Stenmark-Askmalm, Marie, Olopade, Olufunmilayo I., Nussbaum, Robert L., Rebbeck, Timothy R., Nathanson, Katherine L., Domchek, Susan M., Lu, Karen H., Karlan, Beth Y., Walsh, Christine, Lester, Jenny, Hein, Alexander, Ekici, Arif B., Beckmann, Matthias W., Fasching, Peter A., Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Lambrechts, Sandrina, Dicks, Ed, Doherty, Jennifer A., Wicklund, Kristine G., Rossing, Mary Anne, Rudolph, Anja, Chang-Claude, Jenny, Wang-Gohrke, Shan, Eilber, Ursula, Moysich, Kirsten B., Odunsi, Kunle, Sucheston, Lara, Lele, Shashi, Wilkens, Lynne R., Goodman, Marc T., Thompson, Pamela J., Shvetsov, Yurii B., Runnebaum, Ingo B., Duerst, Matthias, Hillemanns, Peter, Doerk, Thilo, Antonenkova, Natalia, Bogdanova, Natalia, Leminen, Arto, Pelttari, Liisa M., Butzow, Ralf, Modugno, Francesmary, Kelley, Joseph L., Edwards, Robert P., Ness, Roberta B., du Bois, Andreas, Heitz, Florian, Schwaab, Ira, Harter, Philipp, Matsuo, Keitaro, Hosono, Satoyo, Orsulic, Sandra, Jensen, Allan, Kjaer, Susanne Kruger, Hogdall, Estrid, Hasmad, Hanis Nazihah, Azmi, Mat Adenan Noor, Teo, Soo-Hwang, Woo, Yin-Ling, Fridley, Brooke L., Goode, Ellen L., Cunningham, Julie M., Vierkant, Robert A., Bruinsma, Fiona, Giles, Graham G., Liang, Dong, Hildebrandt, Michelle A. T., Wu, Xifeng, Levine, Douglas A., Bisogna, Maria, Berchuck, Andrew, Iversen, Edwin S., Schildkraut, Joellen M., Concannon, Patrick, Weber, Rachel Palmieri, Cramer, Daniel W., Terry, Kathryn L., Poole, Elizabeth M., Tworoger, Shelley S., Bandera, Elisa V., Orlow, Irene, Olson, Sara H., Krakstad, Camilla, Salvesen, Helga B., Tangen, Ingvild L., Bjorge, Line, van Altena, Anne M., Aben, Katja K. H., Kiemeney, Lambertus A., Massuger, Leon F. A. 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T., Wu, Xifeng, Levine, Douglas A., Bisogna, Maria, Berchuck, Andrew, Iversen, Edwin S., Schildkraut, Joellen M., Concannon, Patrick, Weber, Rachel Palmieri, Cramer, Daniel W., Terry, Kathryn L., Poole, Elizabeth M., Tworoger, Shelley S., Bandera, Elisa V., Orlow, Irene, Olson, Sara H., Krakstad, Camilla, Salvesen, Helga B., Tangen, Ingvild L., Bjorge, Line, van Altena, Anne M., Aben, Katja K. H., Kiemeney, Lambertus A., Massuger, Leon F. A. 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- Abstract
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 x 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
- Published
- 2015
35. Abstract 1380: Genome-wide fingerprinting of regulatory chromatin to evaluate the tissue specific origins of high-grade serous ovarian cancer
- Author
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Shen, Howard C., primary, Coetzee, Simon, additional, Hazelett, Dennis J., additional, Coetzee, Gerhard A., additional, Noushmehr, Houtan, additional, and Gayther, Simon A., additional
- Published
- 2014
- Full Text
- View/download PDF
36. Galeterone Prevents Androgen Receptor Binding to Chromatin and Enhances Degradation of Mutant Androgen Receptor
- Author
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Yu, Ziyang, primary, Cai, Changmeng, additional, Gao, Shuai, additional, Simon, Nicholas I., additional, Shen, Howard C., additional, and Balk, Steven P., additional
- Published
- 2014
- Full Text
- View/download PDF
37. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
- Author
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A., Gayther, Simon A., Pharoah, Paul D. P., Reddel, Roger R., Goode, Ellen L., Greene, Mark H., Easton, Douglas F., Berchuck, Andrew, Antoniou, Antonis C., Chenevix-Trench, Georgia, Dunning, Alison M., Bojesen, Stig E., Pooley, Karen A., Johnatty, Sharon E., Beesley, Jonathan, Michailidou, Kyriaki, Tyrer, Jonathan P., Edwards, Stacey L., Pickett, Hilda A., Shen, Howard C., Smart, Chanel E., Hillman, Kristine M., Mai, Phuong L., Lawrenson, Kate, Stutz, Michael D., Lu, Yi, Karevan, Rod, Woods, Nicholas, Johnstonw, Rebecca L., French, Juliet D., Chen, Xiaoqing, Weischer, Maren, Nielsen, Sune F., Maranian, Melanie J., Ghoussaini, Maya, Ahmed, Shahana, Baynes, Caroline, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Healey, Sue, Lush, Michael, Tessier, Daniel C., Vincent, Daniel, Bacot, Francis, Vergote, Ignace, Lambrechts, Sandrina, Despierre, Evelyn, Risch, Harvey A., Gonzalez-Neira, Anna, Rossing, Mary Anne, Pita, Guillermo, Doherty, Jennifer A., Alvarez, Nuria, Larson, Melissa C., Fridley, Brooke L., Schoof, Nils, Chang-Claude, Jenny, Cicek, Mine S., Peto, Julian, Kalli, Kimberly R., Broeks, Annegien, Armasu, Sebastian M., Schmidt, Marjanka K., Braaf, Linde M., Winterhoff, Boris, Nevanlinna, Heli, Konecny, Gottfried E., Lambrechts, Diether, Rogmann, Lisa, Guenel, Pascal, Teoman, Attila, Milne, Roger L., Garcia, Joaquin J., Cox, Angela, Shridhar, Vijayalakshmi, Burwinkel, Barbara, Marme, Frederik, Hein, Rebecca, Sawyer, Elinor J., Haiman, Christopher A., Wang-Gohrke, Shan, Andrulis, Irene L., Moysich, Kirsten B., Hopper, John L., Odunsi, Kunle, Lindblom, Annika, Giles, Graham G., Brenner, Hermann, Simard, Jacques, Lurie, Galina, Fasching, Peter A., Carney, Michael E., Radice, Paolo, Wilkens, Lynne R., Swerdlow, Anthony, Goodman, Marc T., Brauch, Hiltrud, Garcia-Closas, Montserrat, Hillemanns, Peter, Winqvist, Robert, Durst, Matthias, Devilee, Peter, Runnebaum, Ingo, Jakubowska, Anna, Lubinski, Jan, Mannermaa, Arto, Butzow, Ralf, Bogdanova, Natalia V., Doerk, Thilo, Pelttari, Liisa M., Zheng, Wei, Leminen, Arto, Anton-Culver, Hoda, Bunker, Clareann H., Kristensen, Vessela, Ness, Roberta B., Muir, Kenneth, Edwards, Robert, Meindl, Alfons, Heitz, Florian, Matsuo, Keitaro, du Bois, Andreas, Wu, Anna H., Harter, Philipp, Teo, Soo-Hwang, Schwaab, Ira, Shu, Xiao-Ou, Blot, William, Hosono, Satoyo, Kang, Daehee, Nakanishi, Toru, Hartman, Mikael, Yatabe, Yasushi, Hamann, Ute, Karlan, Beth Y., Sangrajrang, Suleeporn, Kjaer, Susanne Kruger, Gaborieau, Valerie, Jensen, Allan, Eccles, Diana, Hogdall, Estrid, Shen, Chen-Yang, Brown, Judith, Woo, Yin Ling, Shah, Mitul, Azmi, Mat Adenan Noor, Luben, Robert, Omar, Siti Zawiah, Czene, Kamila, Vierkant, Robert A., Nordestgaard, Borge G., Flyger, Henrik, Vachon, Celine, Olson, Janet E., Wang, Xianshu, Levine, Douglas A., Rudolph, Anja, Weber, Rachel Palmieri, Flesch-Janys, Dieter, Iversen, Edwin, Nickels, Stefan, Schildkraut, Joellen M., Silva, Isabel Dos Santos, Cramer, Daniel W., Gibson, Lorna, Terry, Kathryn L., Fletcher, Olivia, Vitonis, Allison F., van der Schoot, C. Ellen, Poole, Elizabeth M., Hogervorst, Frans B. L., Tworoger, Shelley S., Liu, Jianjun, Bandera, Elisa V., Li, Jingmei, Olson, Sara H., Humphreys, Keith, Row, Irene, Blomqvist, Carl, Rodriguez-Rodriguez, Lorna, Aittomaki, Kristiina, Salvesen, Helga B., Muranen, Taru A., Wik, Elisabeth, Brouwers, Barbara, Krakstad, Camilla, Wauters, Els, Halle, Mari K., Wildiers, Hans, Kiemeney, Lambertus A., Mulot, Claire, Aben, Katja K., Laurent-Puig, Pierre, Altena, Anne Mvan, Truong, Therese, Massuger, Leon F. A. G., Benitez, Javier, Pejovic, Tanja, Arias Perez, Jose Ignacio, Hoatlin, Maureen, Zamora, M. Pilar, Cook, Linda S., Balasubramanian, Sabapathy P., Kelemen, Linda E., Schneeweiss, Andreas, Le, Nhu D., Sohn, Christof, Brooks-Wilson, Angela, Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Cybulski, Cezary, Henderson, Brian E., Menkiszak, Janusz, Schumacher, Fredrick, Wentzensen, Nicolas, Marchand, Loic Le, Yang, Hannah P., Mulligan, Anna Marie, Glendon, Gord, Engelholm, Svend Aage, Knight, Julia A., Hogdall, Claus K., Apicella, Carmel, Gore, Martin, Tsimiklis, Helen, Song, Honglin, Southey, Melissa C., Jager, Agnes, den Ouweland, Ans M. Wvan, Brown, Robert, Martens, John W. M., Flanagan, James M., Kriege, Mieke, Paul, James, Margolin, Sara, Siddiqui, Nadeem, Severi, Gianluca, Whittemore, Alice S., Baglietto, Laura, McGuire, Valerie, Stegmaier, Christa, Sieh, Weiva, Mueller, Heiko, Arndt, Volker, Labreche, France, Gao, Yu-Tang, Goldberg, Mark S., Yang, Gong, Dumont, Martine, McLaughlin, John R., Hartmann, Arndt, Ekici, Arif B., Beckmann, Matthias W., Phelan, Catherine M., Lux, Michael P., Permuth-Wey, Jenny, Peissel, Bernard, Sellers, Thomas A., Ficarazzi, Filomena, Barile, Monica, Ziogas, Argyrios, Ashworth, Alan, Gentry-Maharaj, Aleksandra, Jones, Michael, Ramus, Susan J., Orr, Nick, Menon, Usha, Pearce, Celeste L., Bruening, Thomas, Pike, Malcolm C., Ko, Yon-Dschun, Lissowska, Jolanta, Figueroa, Jonine, Kupryjanczyk, Jolanta, Chanock, Stephen J., Dansonka-Mieszkowska, Agnieszka, Jukkola-Vuorinen, Arja, Rzepecka, Iwona K., Pylkas, Katri, Bidzinski, Mariusz, Kauppila, Saila, Hollestelle, Antoinette, Seynaeve, Caroline, Tollenaar, Rob A. E. M., Durda, Katarzyna, Jaworska, Katarzyna, Hartikainen, Jaana M., Kosma, Veli-Matti, Kataja, Vesa, Antonenkova, Natalia N., Long, Jirong, Shrubsole, Martha, Deming-Halverson, Sandra, Lophatananon, Artitaya, Siriwanarangsan, Pornthep, Stewart-Brown, Sarah, Ditsch, Nina, Lichtner, Peter, Schmutzler, Rita K., Ito, Hidemi, Iwata, Hiroji, Tajima, Kazuo, Tseng, Chiu-Chen, Stram, Daniel O., van den Berg, David, Yip, Cheng Har, Ikrarn, M. Kamran, Teh, Yew-Ching, Cai, Hui, Lu, Wei, Signorello, Lisa B., Cai, Qiuyin, Noh, Dong-Young, Yoo, Keun-Young, Miao, Hui, Iau, Philip Tsau-Choong, Teo, Yik Ying, McKay, James, Shapiro, Charles, Ademuyiwa, Foluso, Fountzilas, George, Hsiung, Chia-Ni, Yu, Jyh-Cherng, Hou, Ming-Feng, Healey, Catherine S., Luccarini, Craig, Peock, Susan, Stoppa-Lyonnet, Dominique, Peterlongo, Paolo, Rebbeck, Timothy R., Piedmonte, Marion, Singer, Christian F., Friedman, Eitan, Thomassen, Mads, Offit, Kenneth, Hansen, Thomas V. O., Neuhausen, Susan L., Szabo, Csilla I., Blanco, Ignacio, Garber, Judy, Narod, Steven A., Weitzel, Jeffrey N., Montagna, Marco, Olah, Edith, Godwin, Andrew K., Yannoukakos, Drakoulis, Goldgar, David E., Caldes, Trinidad, Imyanitov, Evgeny N., Tihomirova, Laima, Arun, Banu K., Campbell, Ian, Mensenkamp, Arjen R., van Asperen, Christi J., van Roozendaa, Kees E. P., Meijers-Heijboer, Hanne, Collee, J. Margriet, Oosterwijk, Jan C., Hooning, Maartje J., Rookus, Matti A., van der Luijt, Rob B., Os, Theo A. Mvan, Evans, D. Gareth, Frost, Debra, Fineberg, Elena, Barwell, Julian, Walker, Lisa, Kennedy, M. John, Platte, Radka, Davidson, Rosemarie, Ellis, Steve D., Cole, Trevor, Bressac-de Paillerets, Brigitte, Buecher, Bruno, Damiola, Francesca, Faivre, Laurence, Frenay, Marc, Sinilnikova, Olga M., Caron, Olivier, Giraud, Sophie, Mazoyer, Sylvie, Bonadona, Valerie, Caux-Moncoutier, Virginie, Toloczko-Grabarek, Aleksandra, Gronwald, Jacek, Byrski, Tomasz, Spurdle, Amanda B., Bonanni, Bernardo, Zaffaroni, Daniela, Giannini, Giuseppe, Bernard, Loris, Dolcetti, Riccardo, Manoukian, Siranoush, Arnold, Norbert, Engel, Christoph, Deissler, Helmut, Rhiem, Kerstin, Niederacher, Dieter, Pendl, Hansjoerg, Sutter, Christian, Wappenschmidt, Barbara, Borg, Ake, Mein, Beatrice, Rantala, Johanna, Soller, Maria, Nathanson, Katherine L., Domchek, Susan M., Rodriguez, Gustavo C., Salani, Ritu, Kaulich, Daphne Gschwantler, Tea, Muy-Kheng, Paluch, Shani Shimon, Laitman, Yael, Skytte, Anne-Bine, Kruse, Torben A., Jensen, Uffe Birk, Robson, Mark, Gerdes, Anne-Marie, Ejlertsen, Bent, Foretova, Lenka, Savage, Sharon A., Lesterm, Jenny, Soucy, Penny, Kuchenbaecker, Karoline B., Olswold, Curtis, Cunningham, Julie M., Slager, Susan, Pankratz, Vernon S., Dicks, Ed, Lakhani, Sunil R., Couch, Fergus J., Hall, Per, Monteiro, Alvaro N. A., Gayther, Simon A., Pharoah, Paul D. P., Reddel, Roger R., Goode, Ellen L., Greene, Mark H., Easton, Douglas F., Berchuck, Andrew, Antoniou, Antonis C., Chenevix-Trench, Georgia, and Dunning, Alison M.
- Abstract
TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
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- 2013
- Full Text
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38. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer
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Pharoah, Paul D P, Tsai, Ya-Yu, Ramus, Susan J, Phelan, Catherine M, Goode, Ellen L, Lawrenson, Kate, Buckley, Melissa, Fridley, Brooke L, Tyrer, Jonathan P, Shen, Howard, Weber, Rachel, Karevan, Rod, Larson, Melissa C, Song, Honglin, Tessier, Daniel C, Bacot, François, Vincent, Daniel, Cunningham, Julie M, Dennis, Joe, Dicks, Ed, Aben, Katja K, Anton-Culver, Hoda, Antonenkova, Natalia, Armasu, Sebastian M, Baglietto, Laura, Bandera, Elisa V, Beckmann, Matthias W, Birrer, Michael J, Bloom, Greg, Bogdanova, Natalia, Brenton, James D, Brinton, Louise A, Brooks-Wilson, Angela, Brown, Robert James (Jim), Butzow, Ralf, Campbell, Ian, Carney, Michael E, Carvalho, Renato S, Chang-Claude, Jenny, Chen, Y Anne, Chen, Zhihua, Chow, Wong-Ho, Cicek, Mine S, Coetzee, Gerhard, Cook, Linda S, Cramer, Daniel W, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Edwards, Robert, Ekici, Arif B, Fasching, Peter A, Fenstermacher, David, Flanagan, James, Gao, Yu-Tang, Garcia-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Giles, Graham, Gjyshi, Anxhela, Gore, Martin, Gronwald, Jacek, Guo, Qi, Halle, Mari K, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hillemanns, Peter, Hoatlin, Maureen, Høgdall, Estrid, Høgdall, Claus K, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Kalli, Kimberly R, Karlan, Beth Y, Kelemen, Linda E, Kiemeney, Lambertus A, Kjaer, Susanne Krüger, Konecny, Gottfried E, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Nathan, Lee, Janet, Leminen, Arto, Lim, Boon Kiong, Lissowska, Jolanta, Lubi?ski, Jan, Lundvall, Lene, Lurie, Galina, Massuger, Leon F A G, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Nakanishi, Toru, Narod, Steven A, Ness, Roberta B, Nevanlinna, Heli, Nickels, Stefan, Noushmehr, Houtan, Odunsi, Kunle, Olson, Sara, Orlow, Irene, Paul, James, Pejovic, Tanja, Pelttari, Liisa M, Permuth-Wey, Jenny, Pike, Malcolm C, Poole, Elizabeth M, Qu, Xiaotao, Risch, Harvey A, Rodriguez-Rodriguez, Lorna, Rossing, Mary Anne, Rudolph, Anja, Runnebaum, Ingo, Rzepecka, Iwona K, Salvesen, Helga B, Schwaab, Ira, Severi, Gianluca, Shen, Hui, Shridhar, Vijayalakshmi, Shu, Xiao-Ou, Sieh, Weiva, Southey, Melissa C, Spellman, Paul, Tajima, Kazuo, Teo, Soo-Hwang, Terry, Kathryn L, Thompson, Pamela J, Timorek, Agnieszka, Tworoger, Shelley S, van Altena, Anne M, van den Berg, David, Vergote, Ignace, Vierkant, Robert A, Vitonis, Allison F, Wang-Gohrke, Shan, Wentzensen, Nicolas, Whittemore, Alice S, Wik, Elisabeth, Winterhoff, Boris, Woo, Yin Ling, Wu, Anna H, Yang, Hannah P, Zheng, Wei, Ziogas, Argyrios, Zulkifli, Famida, Goodman, Marc T, Hall, Per, Easton, Douglas F, Pearce, Celeste L, Berchuck, Andrew, Chenevix-Trench, Georgia, Iversen, Edwin, Monteiro, Alvaro N A, Gayther, Simon A, Schildkraut, Joellen M, Sellers, Thomas A, Study, Australian Cancer, Pharoah, Paul D P, Tsai, Ya-Yu, Ramus, Susan J, Phelan, Catherine M, Goode, Ellen L, Lawrenson, Kate, Buckley, Melissa, Fridley, Brooke L, Tyrer, Jonathan P, Shen, Howard, Weber, Rachel, Karevan, Rod, Larson, Melissa C, Song, Honglin, Tessier, Daniel C, Bacot, François, Vincent, Daniel, Cunningham, Julie M, Dennis, Joe, Dicks, Ed, Aben, Katja K, Anton-Culver, Hoda, Antonenkova, Natalia, Armasu, Sebastian M, Baglietto, Laura, Bandera, Elisa V, Beckmann, Matthias W, Birrer, Michael J, Bloom, Greg, Bogdanova, Natalia, Brenton, James D, Brinton, Louise A, Brooks-Wilson, Angela, Brown, Robert James (Jim), Butzow, Ralf, Campbell, Ian, Carney, Michael E, Carvalho, Renato S, Chang-Claude, Jenny, Chen, Y Anne, Chen, Zhihua, Chow, Wong-Ho, Cicek, Mine S, Coetzee, Gerhard, Cook, Linda S, Cramer, Daniel W, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Edwards, Robert, Ekici, Arif B, Fasching, Peter A, Fenstermacher, David, Flanagan, James, Gao, Yu-Tang, Garcia-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Giles, Graham, Gjyshi, Anxhela, Gore, Martin, Gronwald, Jacek, Guo, Qi, Halle, Mari K, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hillemanns, Peter, Hoatlin, Maureen, Høgdall, Estrid, Høgdall, Claus K, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Kalli, Kimberly R, Karlan, Beth Y, Kelemen, Linda E, Kiemeney, Lambertus A, Kjaer, Susanne Krüger, Konecny, Gottfried E, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Nathan, Lee, Janet, Leminen, Arto, Lim, Boon Kiong, Lissowska, Jolanta, Lubi?ski, Jan, Lundvall, Lene, Lurie, Galina, Massuger, Leon F A G, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Nakanishi, Toru, Narod, Steven A, Ness, Roberta B, Nevanlinna, Heli, Nickels, Stefan, Noushmehr, Houtan, Odunsi, Kunle, Olson, Sara, Orlow, Irene, Paul, James, Pejovic, Tanja, Pelttari, Liisa M, Permuth-Wey, Jenny, Pike, Malcolm C, Poole, Elizabeth M, Qu, Xiaotao, Risch, Harvey A, Rodriguez-Rodriguez, Lorna, Rossing, Mary Anne, Rudolph, Anja, Runnebaum, Ingo, Rzepecka, Iwona K, Salvesen, Helga B, Schwaab, Ira, Severi, Gianluca, Shen, Hui, Shridhar, Vijayalakshmi, Shu, Xiao-Ou, Sieh, Weiva, Southey, Melissa C, Spellman, Paul, Tajima, Kazuo, Teo, Soo-Hwang, Terry, Kathryn L, Thompson, Pamela J, Timorek, Agnieszka, Tworoger, Shelley S, van Altena, Anne M, van den Berg, David, Vergote, Ignace, Vierkant, Robert A, Vitonis, Allison F, Wang-Gohrke, Shan, Wentzensen, Nicolas, Whittemore, Alice S, Wik, Elisabeth, Winterhoff, Boris, Woo, Yin Ling, Wu, Anna H, Yang, Hannah P, Zheng, Wei, Ziogas, Argyrios, Zulkifli, Famida, Goodman, Marc T, Hall, Per, Easton, Douglas F, Pearce, Celeste L, Berchuck, Andrew, Chenevix-Trench, Georgia, Iversen, Edwin, Monteiro, Alvaro N A, Gayther, Simon A, Schildkraut, Joellen M, Sellers, Thomas A, and Study, Australian Cancer
- Abstract
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10−9) and 10p12 (rs1243180, P = 1.8 × 10−8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10−10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
- Published
- 2013
39. A Radio Frequency Identification (RFID) evaluation strategy for customer fulfillment centers
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Stephen C. Graves and David Simchi-Levi., Leaders for Manufacturing Program., Sloan School of Management., Massachusetts Institute of Technology. Engineering Systems Division., Shen, Howard H. (Howard Hao), Stephen C. Graves and David Simchi-Levi., Leaders for Manufacturing Program., Sloan School of Management., Massachusetts Institute of Technology. Engineering Systems Division., and Shen, Howard H. (Howard Hao)
- Abstract
Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division; in conjunction with the Leaders for Manufacturing Program at MIT, 2006., Includes bibliographical references (leaves 66-67)., Radio Frequency Identification (RFID) is a wireless technology that can be used to track inventory labeled with microchip-embedded identifiers communicating passively with scanners without operator involvement. This non-line-of-sight technology has the potential of dramatically increasing the level of visibility throughout the supply chain for many types of products, assisting in defect reduction, increased granularity in inventory tracking, and decreased direct labor. In recent years, developments in RFID technology have decreased the cost of RFID equipment, and several large U.S. retailers have started to use RFID to track consumer products. However, what is not clear is whether or not these RFID implementations have yielded economic returns. Although RFID promises higher read rates and increased accuracy, how the technology works in particular warehouse settings is not clear. The first step to determining the feasibility of RFID in any organization is the complete evaluation of RFID technology. This document discusses an evaluation strategy using the Six Sigma DMADV framework. The strategy was carried out at internet retailer Amazon.com., (cont.) The document discusses the various steps required for a complete implementation of the evaluation strategy and refers to the evaluation at Amazon.com as a case study. The purpose of this document is to recommend a complete evaluation strategy of RFID system components for any customer fulfillment center that is thinking of implementing this technology to replace existing tracking technologies such as bar code or other manual forms of tracking., by Howard H. Shen., S.M., M.B.A.
- Published
- 2007
40. Structural basis for nuclear receptor corepressor recruitment by antagonist-liganded androgen receptor
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Hodgson, Myles C., primary, Shen, Howard C., additional, Hollenberg, Anthony N., additional, and Balk, Steven P., additional
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- 2008
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41. Locus-Wide Chromatin Remodeling and Enhanced Androgen Receptor-Mediated Transcription in Recurrent Prostate Tumor Cells
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Jia, Li, primary, Shen, Howard C., additional, Wantroba, Marcus, additional, Khalid, Omar, additional, Liang, Gangning, additional, Wang, Qingcai, additional, Gentzschein, Elisabet, additional, Pinski, Jacek K., additional, Stanczyk, Frank Z., additional, Jones, Peter A., additional, and Coetzee, Gerhard A., additional
- Published
- 2006
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42. Expression of Dlx and Lhx family homeobox genes in fetal thymus and thymocytes
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Woodside, Kenneth J., primary, Shen, Howard, additional, Muntzel, Christiana, additional, Daller, John A., additional, Sommers, Connie L., additional, and Love, Paul E., additional
- Published
- 2004
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43. Identification of six new susceptibility loci for invasive epithelial ovarian cancer
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Kuchenbaecker, Karoline B., Ramus, Susan J., Tyrer, Jonathan, Lee, Andrew, Shen, Howard C., Beesley, Jonathan, Lawrenson, Kate, McGuffog, Lesley, Healey, Sue, Lee, Janet M., Spindler, Tassja J., Lin, Yvonne G., Pejovic, Tanja, Bean, Yukie, Li, Qiyuan, Coetzee, Simon, Hazelett, Dennis, Miron, Alexander, Southey, Melissa, Terry, Mary Beth, Goldgar, David E., Buys, Saundra S., Janavicius, Ramunas, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Neuhausen, Susan L., Ding, Yuan Chun, Hansen, Thomas V. O., Jønson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, Barrowdale, Daniel, Dennis, Joe, Benitez, Javier, Osorio, Ana, Garcia, Maria Jose, Komenaka, Ian, Weitzel, Jeffrey N., Ganschow, Pamela, Peterlongo, Paolo, Bernard, Loris, Viel, Alessandra, Bonanni, Bernardo, Peissel, Bernard, Manoukian, Siranoush, Radice, Paolo, Papi, Laura, Ottini, Laura, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Frost, Debra, Perkins, Jo, Platte, Radka, Ellis, Steve, Godwin, Andrew K., Schmutzler, Rita Katharina, Meindl, Alfons, Engel, Christoph, Sutter, Christian, Sinilnikova, Olga M., Damiola, Francesca, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Claes, Kathleen, De Leeneer, Kim, Kirk, Judy, Rodriguez, Gustavo C., Piedmonte, Marion, O'Malley, David M., de la Hoya, Miguel, Caldes, Trinidad, Aittomäki, Kristiina, Nevanlinna, Heli, Collée, J. Margriet, Rookus, Matti A., Oosterwijk, Jan C., Tihomirova, Laima, Tung, Nadine, Hamann, Ute, Isaacs, Claudine, Tischkowitz, Marc, Imyanitov, Evgeny N., Caligo, Maria A., Campbell, Ian, Hogervorst, Frans B.L., Olah, Edith, Diez, Orland, Blanco, Ignacio, Brunet, Joan, Lazaro, Conxi, Pujana, Miquel Angel, Jakubowska, Anna, Gronwald, Jacek, Lubinski, Jan, Sukiennicki, Grzegorz, Barkardottir, Rosa B., Plante, Marie, Simard, Jacques, Soucy, Penny, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R., Pankratz, Vernon S., Wang, Xianshu, Lindor, Noralane, Szabo, Csilla I., Kauff, Noah, Vijai, Joseph, Aghajanian, Carol A., Pfeiler, Georg, Berger, Andreas, Singer, Christian F., Tea, Muy-Kheng, Phelan, Catherine M., Greene, Mark H., Mai, Phuong L., Rennert, Gad, Mulligan, Anna Marie, Tchatchou, Sandrine, Andrulis, Irene L., Glendon, Gord, Toland, Amanda Ewart, Jensen, Uffe Birk, Kruse, Torben A., Thomassen, Mads, Bojesen, Anders, Zidan, Jamal, Friedman, Eitan, Laitman, Yael, Soller, Maria, Liljegren, Annelie, Arver, Brita, Einbeigi, Zakaria, Stenmark-Askmalm, Marie, Olopade, Olufunmilayo I., Nussbaum, Robert L., Rebbeck, Timothy R., Nathanson, Katherine L., Domchek, Susan M., Lu, Karen H., Karlan, Beth Y., Walsh, Christine, Lester, Jenny, Hein, Alexander, Ekici, Arif B., Beckmann, Matthias W., Fasching, Peter A., Lambrechts, Diether, Nieuwenhuysen, Els Van, Vergote, Ignace, Lambrechts, Sandrina, Dicks, Ed, Doherty, Jennifer A., Wicklund, Kristine G., Rossing, Mary Anne, Rudolph, Anja, Chang-Claude, Jenny, Wang-Gohrke, Shan, Eilber, Ursula, Moysich, Kirsten B., Odunsi, Kunle, Sucheston-Campbell, Lara, Lele, Shashi, Wilkens, Lynne R., Goodman, Marc T., Thompson, Pamela J., Shvetsov, Yurii B., Runnebaum, Ingo B., Dürst, Matthias, Hillemanns, Peter, Dörk, Thilo, Antonenkova, Natalia, Bogdanova, Natalia, Leminen, Arto, Pelttari, Liisa M., Butzow, Ralf, Modugno, Francesmary, Kelley, Joseph L., Edwards, Robert P., Ness, Roberta B., du Bois, Andreas, Heitz, Florian, Schwaab, Ira, Harter, Philipp, Matsuo, Keitaro, Hosono, Satoyo, Orsulic, Sandra, Jensen, Allan, Kjaer, Susanne Kruger, Hogdall, Estrid, Hasmad, Hanis Nazihah, Noor Azmi, Mat Adenan, Teo, Soo-Hwang, Woo, Yin-Ling, Fridley, Brooke L., Goode, Ellen L., Cunningham, Julie M., Vierkant, Robert A., Bruinsma, Fiona, Giles, Graham G., Liang, Dong, Hildebrandt, Michelle A.T., Wu, Xifeng, Levine, Douglas A., Bisogna, Maria, Berchuck, Andrew, Iversen, Edwin S., Schildkraut, Joellen M., Concannon, Patrick, Weber, Rachel Palmieri, Cramer, Daniel W., Terry, Kathryn L., Poole, Elizabeth M., Tworoger, Shelley S., Bandera, Elisa V., Orlow, Irene, Olson, Sara H., Krakstad, Camilla, Salvesen, Helga B., Tangen, Ingvild L., Bjorge, Line, van Altena, Anne M., Aben, Katja K.H., Kiemeney, Lambertus A., Massuger, Leon F.A.G., Kellar, Melissa, Brooks-Wilson, Angela, Kelemen, Linda E., Cook, Linda S., Le, Nhu D., Cybulski, Cezary, Yang, Hannah, Lissowska, Jolanta, Brinton, Louise A., Wentzensen, Nicolas, Hogdall, Claus, Lundvall, Lene, Nedergaard, Lotte, Baker, Helen, Song, Honglin, Eccles, Diana, McNeish, Ian, Paul, James, Carty, Karen, Siddiqui, Nadeem, Glasspool, Rosalind, Whittemore, Alice S., Rothstein, Joseph H., McGuire, Valerie, Sieh, Weiva, Ji, Bu-Tian, Zheng, Wei, Shu, Xiao-Ou, Gao, Yu-Tang, Rosen, Barry, Risch, Harvey A., McLaughlin, John R., Narod, Steven A., Monteiro, Alvaro N., Chen, Ann, Lin, Hui-Yi, Permuth-Wey, Jenny, Sellers, Thomas A., Tsai, Ya-Yu, Chen, Zhihua, Ziogas, Argyrios, Anton-Culver, Hoda, Gentry-Maharaj, Aleksandra, Menon, Usha, Harrington, Patricia, Lee, Alice W., Wu, Anna H., Pearce, Celeste L., Coetzee, Gerhard A., Pike, Malcolm C., Dansonka-Mieszkowska, Agnieszka, Timorek, Agnieszka, Rzepecka, Iwona K., Kupryjanczyk, Jolanta, Freedman, Matt, Noushmehr, Houtan, Easton, Douglas F., Offit, Kenneth, Couch, Fergus J., Gayther, Simon, Pharoah, Paul P., Antoniou, Antonis C., and Chenevix-Trench, Georgia
- Published
- 2014
- Full Text
- View/download PDF
44. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer
- Author
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Pharoah, Paul D. P., Tsai, Ya-Yu, Ramus, Susan J., Phelan, Catherine M., Goode, Ellen L., Lawrenson, Kate, Price, Melissa, Fridley, Brooke L., Tyrer, Jonathan P., Shen, Howard, Weber, Rachel, Karevan, Rod, Larson, Melissa C., Song, Honglin, Tessier, Daniel C., Bacot, François, Vincent, Daniel, Cunningham, Julie M., Dennis, Joe, Dicks, Ed, Aben, Katja K., Anton-Culver, Hoda, Antonenkova, Natalia, Armasu, Sebastian M., Baglietto, Laura, Bandera, Elisa V., Beckmann, Matthias W., Birrer, Michael J., Bloom, Greg, Bogdanova, Natalia, Brenton, James D., Brinton, Louise A., Brooks-Wilson, Angela, Brown, Robert, Butzow, Ralf, Campbell, Ian, Carney, Michael E, Carvalho, Renato S., Chang-Claude, Jenny, Chen, Y. Anne, Chen, Zhihua, Chow, Wong-Ho, Cicek, Mine S., Coetzee, Gerhard, Cook, Linda S., Cramer, Daniel W., Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Edwards, Robert, Ekici, Arif B., Fasching, Peter A., Fenstermacher, David, Flanagan, James, Gao, Yu-Tang, Garcia-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Giles, Graham, Gjyshi, Anxhela, Gore, Martin, Gronwald, Jacek, Guo, Qi, Halle, Mari K, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hillemanns, Peter, Hoatlin, Maureen, Høgdall, Estrid, Høgdall, Claus K., Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Kalli, Kimberly R., Karlan, Beth Y., Kelemen, Linda E., Kiemeney, Lambertus A., Kjaer, Susanne Krüger, Konecny, Gottfried E., Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D., Lee, Nathan, Lee, Janet, Leminen, Arto, Lim, Boon Kiong, Lissowska, Jolanta, Lubiński, Jan, Lundvall, Lene, Lurie, Galina, Massuger, Leon F.A.G., Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B., Nakanishi, Toru, Narod, Steven A., Ness, Roberta B., Nevanlinna, Heli, Nickels, Stefan, Noushmehr, Houtan, Odunsi, Kunle, Olson, Sara, Orlow, Irene, Paul, James, Pejovic, Tanja, Pelttari, Liisa M, Permuth-Wey, Jenny, Pike, Malcolm C, Poole, Elizabeth M, Qu, Xiaotao, Risch, Harvey A., Rodriguez-Rodriguez, Lorna, Rossing, Mary Anne, Rudolph, Anja, Runnebaum, Ingo, Rzepecka, Iwona K, Salvesen, Helga B., Schwaab, Ira, Severi, Gianluca, Shen, Hui, Shridhar, Vijayalakshmi, Shu, Xiao-Ou, Sieh, Weiva, Southey, Melissa C., Spellman, Paul, Tajima, Kazuo, Teo, Soo-Hwang, Terry, Kathryn L., Thompson, Pamela J, Timorek, Agnieszka, Tworoger, Shelley S., van Altena, Anne M., Berg, David Van Den, Vergote, Ignace, Vierkant, Robert A., Vitonis, Allison F., Wang-Gohrke, Shan, Wentzensen, Nicolas, Whittemore, Alice S., Wik, Elisabeth, Winterhoff, Boris, Woo, Yin Ling, Wu, Anna H, Yang, Hannah P., Zheng, Wei, Ziogas, Argyrios, Zulkifli, Famida, Goodman, Marc T., Hall, Per, Easton, Douglas F, Pearce, Celeste L, Berchuck, Andrew, Chenevix-Trench, Georgia, Iversen, Edwin, Monteiro, Alvaro N.A., Gayther, Simon A., Schildkraut, Joellen M., and Sellers, Thomas A.
- Abstract
Genome wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC) with another two loci being close to genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the United Kingdom. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. Follow-up genotyping was carried out in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 previously near genome-wide significance and identified three novel loci associated with risk; two loci associated with all EOC subtypes, at 8q21 (rs11782652, P=5.5×10-9) and 10p12 (rs1243180; P=1.8×10-8), and another locus specific to the serous subtype at 17q12 (rs757210; P=8.1×10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility that implicates CHMP4C in the pathogenesis of ovarian cancer.
- Published
- 2013
- Full Text
- View/download PDF
45. Locus-Wide Chromatin Remodeling and Enhanced Androgen Receptor-Mediated Transcription in Recurrent Prostate Tumor Cells.
- Author
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Li Jia, Shen, Howard C., Wantroba, Marcus, Khalid, Omar, Liang, Gangning, Wang, Qingcai, Gentzschein, Elisabet, Pinski, Jacek K., Stanczyk, Frank Z., Jones, Peter A., and Coetzee, Gerhard A.
- Subjects
- *
PROSTATE cancer , *ANDROGENS , *CELLS , *HISTONES , *MOLECULAR genetics - Abstract
Prostate cancers (PCas) become resistant to hormone withdrawal through increased androgen receptor (AR) signaling. Here we show increased AR-mediated transcription efficiency in PCa cells that have acquired the ability to grow in low concentrations of androgen. Compared to androgen-dependent PCa cells, these cells showed increased activity of transiently transfected reporters and increased mRNA synthesis relative to levels of AR occupancy of the prostate-specific antigen (PSA) gene. The locus also displayed up to 10-fold-higher levels of histone H3-K9/K14 acetylation and H3-K4 methylation across the entire body of the gene. Although similar increased mRNA expression and locus-wide histone acetylation were also observed at another kallikrein locus (KLK2), at a third AR target locus (TMPRSS2) increased gene expression and locus-wide histone acetylation were not seen in the absence of ligand. Androgen-independent PCa cells have thus evolved three distinctive alterations in AR-mediated transcription. First, increased RNA polymerase initiation and processivity contributed to increased gene expression. Second, AR signaling was more sensitive to ligand. Third, locus-wide chromatin remodeling conducive to the increased gene expression in the absence of ligand was apparent and depended on sustained AR activity. Therefore, increased AR ligand sensitivity as well as locus-specific chromatin alterations contribute to basal gene expression of a subpopulation of specific AR target genes in androgen-independent PCa cells. These features contribute to the androgen-independent phenotype of these cells. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
46. Cross-Seeding Assay in the Investigation of the Amyloid Core of Prion Fibrils.
- Author
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Chu BK, Lin YS, Shen HC, and Chen RP
- Subjects
- Humans, Amyloid chemistry, Amyloidogenic Proteins, Prions chemistry, Amyloidosis, Prion Diseases
- Abstract
Amyloidogenesis, self-propagation of protein or peptide monomers to amyloid fibrils, has been linked to incurable pathogenesis of neurodegenerative diseases such as Alzheimer's disease and prion diseases. Investigations of amyloid structures and how monomers are transformed through seeding are therefore crucial for developing therapeutics toward these diseases. Here we describe a cross-seeding method to explore the amyloid core in prion fibrils that uses preformed amyloid fibrils as a seed to induce the transformation of other protein or peptide monomers to amyloid fibrils., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
47. Androgen receptor activity at the prostate specific antigen locus: steroidal and non-steroidal mechanisms.
- Author
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Jia L, Kim J, Shen H, Clark PE, Tilley WD, and Coetzee GA
- Subjects
- Acetylation, Adenylyl Cyclases metabolism, Cell Division physiology, Colforsin pharmacology, Dihydrotestosterone metabolism, Genes, Reporter, Histones metabolism, Humans, Interleukin-6 metabolism, Interleukin-6 pharmacology, Ligands, Luciferases genetics, Male, Promoter Regions, Genetic, Prostate-Specific Antigen genetics, Receptors, Androgen genetics, Tumor Cells, Cultured, Dihydrotestosterone pharmacology, Prostate-Specific Antigen metabolism, Prostatic Neoplasms, Receptors, Androgen metabolism
- Abstract
Ligand-activated androgen receptors (ARs) occupy target genes and recruit histone modifiers that influence transcriptional competency. In LNCaP prostate cancer cells, the natural ligand 5alpha-dihydrotestosterone (DHT) activates transiently transfected AR-responsive promoter constructs; concurrent treatment with the protein kinase A activator forskolin enhanced AR stimulation induced by DHT. Additional treatment with the cytokine IL-6, purportedly an AR activator, markedly inhibited receptor activity. To assess AR activity on natural chromatin-integrated promoters/enhancers, we determined AR occupancy of the endogenous prostate specific antigen (PSA) promoter/enhancer as well as PSA expression in LNCaP cells treated with DHT; AR occupancy of the PSA enhancer was rapid (within 1 h of stimulation), robust (10-fold over background), and sustained (8-16 h). In contrast, AR occupancy of the PSA promoter was only increased by 2-fold. Histone H3 acetylation at both the enhancer and promoter was evident 1-2 h after DHT treatment. Detectable pre- and mature PSA mRNA levels appeared after 1 and 6 h treatment, respectively. Substantial qualitative and quantitative differences in PSA expression and AR occupancy of the PSA enhancer were observed when DHT-induced and ligand-independent activations of the AR were compared; forskolin stimulated PSA mRNA and protein expression, whereas IL-6 inhibited both DHT- and forskolin-stimulated expression. IL-6 did not diminish DHT-dependent AR occupancy of the PSA enhancer but inhibited CBP/p300 recruitment, histone H3 acetylation, and cell proliferation. These findings provide a contextual framework for interpreting the contribution of non-steroidal activation of the AR to signaling in vivo, and have implications for prostate cancer cell growth.
- Published
- 2003
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