Genetically Predicted Levels of DNA Methylation Biomarkers and Breast Cancer Risk: Data From 228 951 Women of European Descent
Yaohua Yang,Lang Wu,Xiao-Ou Shu,Qiuyin Cai,Xiang Shu,Bingshan Li,Xingyi Guo,Fei Ye,Kyriaki Michailidou,Manjeet K. Bolla,Qin Wang,Joe Dennis,Irene L. Andrulis,Irene L. Andrulis,Irene L. Andrulis,Hermann Brenner,Georgia Chenevix-Trench,Daniele Campa,Jose E. Castelao,Manuela Gago-Dominguez,Thilo Dörk,Antoinette Hollestelle,Artitaya Lophatananon,Artitaya Lophatananon,Kenneth Muir,Kenneth Muir,Susan L. Neuhausen,Håkan Olsson,Dale P. Sandler,Jacques Simard,Peter Kraft,Paul D.P. Pharoah,Douglas F. Easton,Wei Zheng,Jirong Long +34 more
TL;DR: In this article, a new methodology was proposed to identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases, including other diseases such as cancer.
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Abstract: BACKGROUND: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk. METHODS: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women's Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided. RESULTS: Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10-7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes. CONCLUSION: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases. (Less)
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Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
- 01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
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Personalized early detection and prevention of breast cancer: ENVISION consensus statement.
Nora Pashayan,Antonis C. Antoniou,Urška Ivanuš,Laura J. Esserman,Douglas F. Easton,David P. French,Gaby Sroczynski,Per Hall,Jack Cuzick,D. Gareth Evans,Jacques Simard,Montserrat Garcia-Closas,Rita K. Schmutzler,Odette Wegwarth,Paul D.P. Pharoah,Sowmiya Moorthie,Sandrine De Montgolfier,Camille Baron,Zdenko Herceg,Clare Turnbull,Corinne Balleyguier,Paolo Giorgi Rossi,Jelle Wesseling,David Ritchie,Marc Tischkowitz,Mireille J. M. Broeders,Daniel Reisel,Andres Metspalu,Thomas Callender,Harry J. de Koning,Peter Devilee,Suzette Delaloge,Marjanka K. Schmidt,Martin Widschwendter +33 more
TL;DR: This Consensus Statement discusses the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation and presents recommendations on priorities for future research in each of these areas with the aim of stimulating and guiding risk-adapted breast cancer prevention and screening programmes.
An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk.
Lang Wu,Yaohua Yang,Xingyi Guo,Xiao-Ou Shu,Qiuyin Cai,Xiang Shu,Bingshan Li,Bingshan Li,Ran Tao,Chong Wu,Jason B. Nikas,Yanfa Sun,Yanfa Sun,Jingjing Zhu,Monique J. Roobol,Graham G. Giles,Graham G. Giles,Hermann Brenner,Esther M. John,Judith A. Clements,Judith A. Clements,Eli Marie Grindedal,Jong Y. Park,Janet L. Stanford,Janet L. Stanford,Zsofia Kote-Jarai,Christopher A. Haiman,Rosalind A. Eeles,Wei Zheng,Jirong Long +29 more
TL;DR: DNA methylation biomarkers associated with PrCa are identified and the findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.
MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer
TL;DR: It is illustrated how epigenetic instability orchestrates the attainment of cancer hallmarks which stimulate the neoplastic transformation-tumorigenesis-malignancy cascades and reversibility of epigenetic controls is a promising feature to optimize for devising novel therapeutic approaches.
100
Epigenome-wide DNA methylation and risk of breast cancer: a systematic review.
TL;DR: A systematic analysis of the findings of epigenome-wide DNA methylation studies on breast cancer risk, in light of their methodological strengths and weaknesses found a consistent trend toward an association of global blood-derived DNA hypomethylation and higher epigenetic age with higher risk of breast cancer.
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Daniel C. Koboldt,Robert S. Fulton,Michael D. McLellan,Heather Schmidt,Joelle Kalicki-Veizer,Joshua F. McMichael,Lucinda Fulton,David J. Dooling,Li Ding,Elaine R. Mardis,Richard K. Wilson,Adrian Ally,Miruna Balasundaram,Yaron S.N. Butterfield,Rebecca Carlsen,Candace Carter,Andy Chu,Eric Chuah,Hye Jung E. Chun,Robin J.N. Coope,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Jacqueline E. Schein,Arash Shafiei,Payal Sipahimalani,Jared R. Slobodan,Dominik Stoll,Angela Tam,Nina Thiessen,Richard Varhol,Natasja Wye,Thomas Zeng,Yongjun Zhao,Inanc Birol,Steven J.M. Jones,Marco A. Marra,Andrew D. Cherniack,Gordon Saksena,Gordon Saksena,Robert C. Onofrio,Nam H. Pho,Scott L. Carter,Steven E. Schumacher,Steven E. Schumacher,Barbara Tabak,Barbara Tabak,Bryan Hernandez,Jeff Gentry,Huy Nguyen,Andrew Crenshaw,Kristin G. 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Teresiak,Honorata Tatka,Ewa Leporowska,Marta Bogusz-Czerniewicz,Julian Malicki,Andrzej Mackiewicz,Maciej Wiznerowicz,Xuan Van Le,Bernard Kohl,Nguyen Viet Tien,Richard Thorp,Nguyen Van Bang,Howard H. Sussman,Bui Duc Phu,Richard A. Hajek,Nguyen Phi Hung,Huynh Quyet Thang,Khurram Z. Khan,Robert Penny,David Mallery,Erin Curley,Candace Shelton,Peggy Yena,James N. Ingle,Fergus J. Couch,Wilma L. Lingle,Tari A. King,Ana M. Gonzalez-Angulo,Ana M. Gonzalez-Angulo,Mary D. Dyer,Shuying Liu,Xiaolong Meng,Modesto Patangan,Frederic Waldman,Frederic Waldman,Hubert Stoppler,W. Kimryn Rathmell,Leigh B. Thorne,Mei Huang,Lori Boice,Ashley Hill,Carl Morrison,Carmelo Gaudioso,Wiam Bshara,Kelly Daily,Sophie C. Egea,Mark D. Pegram,Carmen Gomez-Fernandez,Rajiv Dhir,Rohit Bhargava,Adam Brufsky,Craig D. Shriver,Jeffrey A. Hooke,Jamie Leigh Campbell,Richard J. Mural,Hai Hu,Stella Somiari,Caroline Larson,Brenda Deyarmin,Leonid Kvecher,Albert J. Kovatich,Matthew J. Ellis,Thomas Stricker,Kevin P. White,Olufunmilayo I. Olopade,Chunqing Luo,Yaqin Chen,Ron Bose,Li-Wei Chang,Andrew H. Beck,Todd Pihl,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Brenda Ayala,Mark Backus,Jessica Walton,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,David Pot,Margi Sheth,John A. Demchok,Kenna R. Mills Shaw,Liming Yang,Greg Eley,Martin L. Ferguson,Roy Tarnuzzer,Jiashan Zhang,Laura A.L. Dillon,Kenneth H. Buetow,Peter Fielding,Bradley A. Ozenberger,Mark S. Guyer,Heidi J. Sofia,Jacqueline D. Palchik +355 more
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Wouter Meuleman,Jason Ernst,Misha Bilenky,Angela Yen,Angela Yen,Alireza Heravi-Moussavi,Pouya Kheradpour,Pouya Kheradpour,Zhizhuo Zhang,Zhizhuo Zhang,Jianrong Wang,Jianrong Wang,Michael J. Ziller,Viren Amin,John W. Whitaker,Matthew D. Schultz,Lucas D. Ward,Lucas D. Ward,Abhishek Sarkar,Abhishek Sarkar,Gerald Quon,Gerald Quon,Richard Sandstrom,Matthew L. Eaton,Matthew L. Eaton,Yi-Chieh Wu,Yi-Chieh Wu,Andreas R. Pfenning,Andreas R. Pfenning,Xinchen Wang,Xinchen Wang,Melina Claussnitzer,Melina Claussnitzer,Yaping Liu,Yaping Liu,Cristian Coarfa,R. Alan Harris,Noam Shoresh,Charles B. Epstein,Elizabeta Gjoneska,Elizabeta Gjoneska,Danny Leung,Wei Xie,R. David Hawkins,Ryan Lister,Chibo Hong,Philippe Gascard,Andrew J. Mungall,Richard A. Moore,Eric Chuah,Angela Tam,Theresa K. Canfield,R. Scott Hansen,Rajinder Kaul,Peter J. Sabo,Mukul S. Bansal,Mukul S. Bansal,Mukul S. Bansal,Annaick Carles,Jesse R. Dixon,Kai How Farh,Soheil Feizi,Soheil Feizi,Rosa Karlic,Ah Ram Kim,Ah Ram Kim,Ashwinikumar Kulkarni,Daofeng Li,Rebecca F. Lowdon,Ginell Elliott,Tim R. Mercer,Shane Neph,Vitor Onuchic,Paz Polak,Paz Polak,Nisha Rajagopal,Pradipta R. Ray,Richard C Sallari,Richard C Sallari,Kyle Siebenthall,Nicholas A Sinnott-Armstrong,Nicholas A Sinnott-Armstrong,Michael Stevens,Robert E. Thurman,Jie Wu,Bo Zhang,Xin Zhou,Arthur E. Beaudet,Laurie A. Boyer,Philip L. De Jager,Philip L. De Jager,Peggy J. Farnham,Susan J. Fisher,David Haussler,Steven J.M. Jones,Steven J.M. Jones,Wei Li,Marco A. Marra,Michael T. McManus,Shamil R. Sunyaev,Shamil R. Sunyaev,James A. Thomson,Thea D. Tlsty,Li-Huei Tsai,Li-Huei Tsai,Wei Wang,Robert A. Waterland,Michael Q. Zhang,Lisa Helbling Chadwick,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein,Joseph F. Costello,Joseph R. Ecker,Martin Hirst,Alexander Meissner,Aleksandar Milosavljevic,Bing Ren,John A. Stamatoyannopoulos,Ting Wang,Manolis Kellis,Manolis Kellis +123 more
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.