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Keun-Young Yoo

Other affiliations: Seoul National University
Bio: Keun-Young Yoo is an academic researcher from New Generation University College. The author has contributed to research in topics: Breast cancer & Cancer. The author has an hindex of 9, co-authored 9 publications receiving 3137 citations. Previous affiliations of Keun-Young Yoo include Seoul National University.

Papers
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Journal ArticleDOI
Douglas F. Easton1, Karen A. Pooley1, Alison M. Dunning1, Paul D.P. Pharoah1, Deborah J. Thompson1, Dennis G. Ballinger, Jeffery P. Struewing2, Jonathan J. Morrison1, Helen I. Field1, Robert Luben1, Nicholas J. Wareham1, Shahana Ahmed1, Catherine S. Healey1, Richard Bowman, Kerstin B. Meyer1, Christopher A. Haiman3, Laurence K. Kolonel, Brian E. Henderson3, Loic Le Marchand, Paul Brennan4, Suleeporn Sangrajrang, Valerie Gaborieau4, Fabrice Odefrey4, Chen-Yang Shen5, Pei-Ei Wu5, Hui-Chun Wang5, Diana Eccles6, D. Gareth Evans7, Julian Peto8, Olivia Fletcher9, Nichola Johnson9, Sheila Seal, Michael R. Stratton10, Nazneen Rahman, Georgia Chenevix-Trench11, Georgia Chenevix-Trench12, Stig E. Bojesen13, Børge G. Nordestgaard13, C K Axelsson13, Montserrat Garcia-Closas2, Louise A. Brinton2, Stephen J. Chanock2, Jolanta Lissowska14, Beata Peplonska15, Heli Nevanlinna16, Rainer Fagerholm16, H Eerola16, Daehee Kang17, Keun-Young Yoo17, Dong-Young Noh17, Sei Hyun Ahn18, David J. Hunter19, Susan E. Hankinson19, David G. Cox19, Per Hall20, Sara Wedrén20, Jianjun Liu21, Yen-Ling Low21, Natalia Bogdanova22, Peter Schu¨rmann22, Do¨rk Do¨rk22, Rob A. E. M. Tollenaar23, Catharina E. Jacobi23, Peter Devilee23, Jan G. M. Klijn24, Alice J. Sigurdson2, Michele M. Doody2, Bruce H. Alexander25, Jinghui Zhang2, Angela Cox26, Ian W. Brock26, Gordon MacPherson26, Malcolm W.R. Reed26, Fergus J. Couch27, Ellen L. Goode27, Janet E. Olson27, Hanne Meijers-Heijboer28, Hanne Meijers-Heijboer24, Ans M.W. van den Ouweland24, André G. Uitterlinden24, Fernando Rivadeneira24, Roger L. Milne29, Gloria Ribas29, Anna González-Neira29, Javier Benitez29, John L. Hopper30, Margaret R. E. McCredie31, Margaret R. E. McCredie11, Margaret R. E. McCredie32, Melissa C. Southey11, Melissa C. Southey30, Graham G. Giles33, Chris Schroen30, Christina Justenhoven34, Christina Justenhoven35, Hiltrud Brauch34, Hiltrud Brauch35, Ute Hamann36, Yon-Dschun Ko, Amanda B. Spurdle12, Jonathan Beesley12, Xiaoqing Chen12, _ kConFab37, Arto Mannermaa37, Veli-Matti Kosma37, Vesa Kataja37, Jaana M. Hartikainen37, Nicholas E. Day1, David Cox, Bruce A.J. Ponder1 
28 Jun 2007-Nature
TL;DR: To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.
Abstract: Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2.0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P,1027). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P,0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

2,288 citations

Journal ArticleDOI
Shahana Ahmed1, Gilles Thomas2, Maya Ghoussaini1, Catherine S. Healey1, Manjeet K. Humphreys1, Radka Platte1, Jonathan J. Morrison1, Melanie Maranian1, Karen A. Pooley1, Robert Luben1, Diana Eccles3, D. Gareth Evans4, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Michael R. Stratton5, Nazneen Rahman, Kevin B. Jacobs2, Kevin B. Jacobs6, Ross L. Prentice7, Garnet L. Anderson7, Aleksandar Rajkovic8, J. David Curb9, Regina G. Ziegler2, Christine D. Berg2, Saundra S. Buys10, Catherine A. McCarty11, Heather Spencer Feigelson12, Eugenia E. Calle12, Michael J. Thun12, W. Ryan Diver12, Stig E. Bojesen13, Børge G. Nordestgaard13, Henrik Flyger13, Thilo Dörk14, Peter Schürmann14, Peter Hillemanns14, Johann H. Karstens14, Natalia Bogdanova14, Natalia Antonenkova, Iosif V. Zalutsky, Marina Bermisheva14, S. A. Fedorova15, Elza Khusnutdinova, Daehee Kang16, Keun-Young Yoo16, Dong Young Noh16, Sei Hyun Ahn16, Peter Devilee17, Christi J. van Asperen17, R.A.E.M. Tollenaar17, Caroline Seynaeve18, Montserrat Garcia-Closas2, Jolanta Lissowska19, Louise A. Brinton2, Beata Peplonska20, Heli Nevanlinna21, Tuomas Heikkinen21, Kristiina Aittomäki21, Carl Blomqvist21, John L. Hopper22, Melissa C. Southey22, Letitia D. Smith23, Amanda B. Spurdle23, Marjanka K. Schmidt24, Annegien Broeks24, Richard van Hien24, Sten Cornelissen24, Roger L. Milne25, Gloria Ribas25, Anna González-Neira25, Javier Benitez25, Rita K. Schmutzler26, Barbara Burwinkel27, Barbara Burwinkel28, Claus R. Bartram27, Alfons Meindl29, Hiltrud Brauch30, Hiltrud Brauch31, Christina Justenhoven31, Christina Justenhoven30, Ute Hamann28, Jenny Chang-Claude28, Rebecca Hein28, Shan Wang-Gohrke32, Annika Lindblom33, Sara Margolin33, Arto Mannermaa34, Veli-Matti Kosma34, Vesa Kataja34, Janet E. Olson35, Xianshu Wang35, Zachary S. Fredericksen35, Graham G. Giles22, Graham G. Giles36, Gianluca Severi36, Gianluca Severi22, Laura Baglietto22, Laura Baglietto36, Dallas R. English22, Dallas R. English25, Susan E. Hankinson37, David G. Cox37, Peter Kraft37, Lars J. Vatten38, Kristian Hveem38, Merethe Kumle, Alice J. Sigurdson2, Michele M. Doody2, Parveen Bhatti2, Bruce H. Alexander39, Maartje J. Hooning18, Ans M.W. van den Ouweland18, Rogier A. Oldenburg18, Mieke Schutte18, Per Hall33, Kamila Czene33, Jianjun Liu40, Yuqing Li40, Angela Cox41, Graeme Elliott41, Ian W. Brock41, Malcolm W.R. Reed41, Chen-Yang Shen42, Chen-Yang Shen43, Jyh Cherng Yu44, Giu Cheng Hsu44, Shou Tung Chen, Hoda Anton-Culver45, Argyrios Ziogas45, Irene L. Andrulis46, Julia A. Knight46, Jonathan Beesley23, Ellen L. Goode35, Fergus J. Couch35, Georgia Chenevix-Trench23, Robert N. Hoover2, Bruce A.J. Ponder47, Bruce A.J. Ponder1, David J. Hunter37, Paul D.P. Pharoah1, Alison M. Dunning1, Stephen J. Chanock2, Douglas F. Easton1 
TL;DR: Strong evidence is found for additional susceptibility loci on 3p and 17q and potential causative genes include SLC4A7 and NEK10 on3p and COX11 on 17q.
Abstract: Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.

480 citations

Journal ArticleDOI
TL;DR: Kim et al. as discussed by the authors showed that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women and provided strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.
Abstract: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent. To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls. In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14). This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.

136 citations

Journal ArticleDOI
TL;DR: Considering interactions between BPA exposure and risks of breast cancer, it is suggested further enlarged biomonitoring studies of BPA to provide effective prevention against breast cancer.
Abstract: The incidence of breast cancer in Korea has been increasing for the last two decades (1983–2005), and now, breast cancer is ranked the leading cause of cancer in Korean women. Along with other endocrine disrupting chemicals (EDCs), bisphenol A (BPA) has been suspected as a potential risk factor for breast cancer. We studied potential associations between BPA exposure and breast cancer risks in Korean women by performing biomonitoring of BPA among breast cancer patients and controls (N = 167). Blood samples were collected between 1994 and 1997 and kept over 10 years in a freezer under well controlled conditions. The blood BPA levels determined by HPLC/FD, ranged between LOD (0.012 µg/L) and 13.87 µg/L (mean ± SD, 1.69 ± 2.57 µg/L; median, 0.043 µg/L). In age-matched subjects (N = 152), there were some associations between BPA levels and risks of breast cancer, such as age at first birth and null parity. However, there were no significant differences in blood BPA levels between the cases and the controls (P = 0.42). Considering interactions between BPA exposure and risks of breast cancer, we suggest further enlarged biomonitoring studies of BPA to provide effective prevention against breast cancer.

132 citations

Journal ArticleDOI
TL;DR: The results suggest that polymorphisms or haplotypes of the ATM gene play an important role in the development of lung cancer.
Abstract: The ataxia telangiectasia mutated (ATM) gene is known to be activated by DNA damage and involved in cell cycle arrest, apoptosis and DNA repair. Therefore, ATM gene polymorphisms may act as important factors predicting individual susceptibility to lung cancer. To evaluate the role of ATM gene polymorphisms in lung cancer development, genotypes of the ATM polymorphisms, 24518A>G, IVS21 2 77C>T, IVS61 2 55T>C, and IVS62 1 60G>A, were determined in 616 lung cancer patients and 616 cancer-free controls. When the effects of selected ATM genotypes were evaluated separately, only one ATM genotype (IVS62 1 60G>A) showed an association with lung cancer risk. Subjects with the A allele at the site (IVS62 1 60G>A) have significantly higher risk of lung cancer than those with the G allele [odds ratio (OR) 5 1.6, 95% confidence interval (CI) 1.1‐2.1]. When the haplotypes of four ATM single nucleotide polymorphism sites (24518A>G, IVS21 2 77C>T, IVS61 2 55T>C and IVS62 1 60G>A) were studied, the ATTA haplotype showed significantly increased risk of lung cancer compared with the GCCA haplotype, the most common haplotype (OR 5 7.6, 95% CI 1.7‐33.5). Furthermore, subjects with the (NN)TA haplotype showed highly significant and increased risk of lung cancer when compared with those without the (NN)TA haplotype (OR 5 13.2, 95% CI 3.1‐56.1). Therefore, our results suggest that polymorphisms or haplotypes of the ATM gene play an important role in the development of lung cancer.

76 citations


Cited by
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08 Oct 2009-Nature
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

7,797 citations

Journal ArticleDOI
TL;DR: This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.
Abstract: The past year has witnessed substantial advances in understanding the genetic basis of many common phenotypes of biomedical importance. These advances have been the result of systematic, well-powered, genome-wide surveys exploring the relationships between common sequence variation and disease predisposition. This approach has revealed over 50 disease-susceptibility loci and has provided insights into the allelic architecture of multifactorial traits. At the same time, much has been learned about the successful prosecution of association studies on such a scale. This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.

2,908 citations

Journal Article
TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.
Abstract: AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore PL02-05 All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

2,737 citations

Journal ArticleDOI
Li Ding1, Gad Getz2, David A. Wheeler3, Elaine R. Mardis1, Michael D. McLellan1, Kristian Cibulskis2, Carrie Sougnez2, Heidi Greulich4, Heidi Greulich2, Donna M. Muzny3, Margaret Morgan3, Lucinda Fulton1, Robert S. Fulton1, Qunyuan Zhang1, Michael C. Wendl1, Michael S. Lawrence2, David E. Larson1, Ken Chen1, David J. Dooling1, Aniko Sabo3, Alicia Hawes3, Hua Shen3, Shalini N. Jhangiani3, Lora Lewis3, Otis Hall3, Yiming Zhu3, Tittu Mathew3, Yanru Ren3, Jiqiang Yao3, Steven E. Scherer3, Kerstin Clerc3, Ginger A. Metcalf3, Brian Ng3, Aleksandar Milosavljevic3, Manuel L. Gonzalez-Garay3, John R. Osborne1, Rick Meyer1, Xiaoqi Shi1, Yuzhu Tang1, Daniel C. Koboldt1, Ling Lin1, Rachel Abbott1, Tracie L. Miner1, Craig Pohl1, Ginger A. Fewell1, Carrie A. Haipek1, Heather Schmidt1, Brian H. Dunford-Shore1, Aldi T. Kraja1, Seth D. Crosby1, Christopher S. Sawyer1, Tammi L. Vickery1, Sacha N. Sander1, Jody S. Robinson1, Wendy Winckler4, Wendy Winckler2, Jennifer Baldwin2, Lucian R. Chirieac4, Amit Dutt4, Amit Dutt2, Timothy Fennell2, Megan Hanna4, Megan Hanna2, Bruce E. Johnson4, Robert C. Onofrio2, Roman K. Thomas5, Giovanni Tonon4, Barbara A. Weir2, Barbara A. Weir4, Xiaojun Zhao2, Xiaojun Zhao4, Liuda Ziaugra2, Michael C. Zody2, Thomas J. Giordano6, Mark B. Orringer6, Jack A. Roth, Margaret R. Spitz7, Ignacio I. Wistuba, Bradley A. Ozenberger8, Peter J. Good8, Andrew C. Chang6, David G. Beer6, Mark A. Watson1, Marc Ladanyi9, Stephen R. Broderick9, Akihiko Yoshizawa9, William D. Travis9, William Pao9, Michael A. Province1, George M. Weinstock1, Harold E. Varmus9, Stacey Gabriel2, Eric S. Lander2, Richard A. Gibbs3, Matthew Meyerson4, Matthew Meyerson2, Richard K. Wilson1 
23 Oct 2008-Nature
TL;DR: Somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B are found.
Abstract: Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

2,615 citations

Journal ArticleDOI
TL;DR: It is concluded that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses, and fundamental changes in chemical testing and safety determination are needed to protect human health.
Abstract: For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...

2,475 citations