Citations 2
Fine‐scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer
Shi, Jiajun , Zhang, Yanfeng , Zheng, Wei , Michailidou, Kyriaki , Ghoussaini, Maya , Bolla, Manjeet K. , Wang, Qin, Beesley, Jonathan, Kar, Siddhartha , Andrulis, Irene L. , Beckmann, Matthias W. , Zhao, Zhiguo , Benı́tez, Javier , Beeghly‐Fadiel, Alicia, Blot, William J. , Bogdanova, Natalia , Bojesen, Stig E. , Brauch, Hiltrud , Brenner, Hermann , Brinton, Louise A. , Brüning, Thomas , Burwinkel, Barbara , Cai, Hui , Canisius, Sander , Chang‐Claude, Jenny , Choi, Ji‐Yeob , Couch, Fergus J. , Darabi, Hatef, Devilee, Peter , Droit, Arnaud , Dörk, Thilo , Fasching, Peter A. , Fletcher, Olivia , Flyger, Henrik, Fostira, Florentia, Gaborieau, Valérie , García‐Closas, Montserrat , Giles, Graham G. , Grip, Mervi, Guénel, Pascal , Haiman, Christopher A., Hamann, Ute, Hartman, Mikael , Miao, Hui , Hopper, John L. , Hsiung, Chia‐Ni , Investigators, kConFab, Jakubowska, Anna , Johnson, Nichola , Torres, Diana , Kabisch, Maria, Kang, Daehee , Khan, Sofia , Knight, Julia A. , Kosma, Veli‐Matti, Lambrechts, Diether , Li, Jingmei , Lindblom, Annika , Lubiński, Jan , Mannermaa, Arto, Manoukian, Siranoush , Margolin, Sara , Matsuo, Keitaro , McLean, Catriona , Meindl, Alfons, Børresen‐Dale, Anne‐Lise , Orr, Nick , Ouweland, Ans M.W. van den, Peterlongo, Paolo , Putti, Thomas Choudary , Sangrajrang, Suleeporn , Sawyer, Elinor J. , Schmidt, Marjanka K. , Schmutzler, Rita K., Shen, Chen‐Yang , Hou, Ming‐Feng , Shrubsole, Matha J., Southey, Melissa C. , Swerdlow, Anthony J. , Teo, Soo‐Hwang , Thienpont, Bernard , Tollenaar, Robert A.E.M., Tomlinson, Ian , Truong, Thérèse , Tseng, Chiu-Chen , Wen, Wanqing , Winqvist, Robert , Wu, Anna H. , Yip, Cheng Har , Zheng, Ying , Floris, Giuseppe , Cheng, Ching‐Yu , Hooning, Maartje J. , Seynaeve, Caroline, Kristensen, Vessela N., Simard, Jacques , Chenevix‐Trench, Georgia , Dunning, Alison M. , Antoniou, Antonis C. , Easton, Douglas F. , Long, Jirong , Durocher, Francine , Thorne, Heather , Shrubsole, Martha J. , Lambrechts, Diether , Wang, Qin, Dennis, Joe , Lush, Michael J. , Milne, Roger L. , Shu, Xiao‐Ou , Anton‐Culver, Hoda , Arndt, Volker , Guo, Xingyi , Beeghly‐Fadiel, Alicia , Broeks, Annegien , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Hollestelle, Antoinette , Investigators, kConFab, Ito, Hidemi , Lophatananon, Artitaya , Mannermaa, Arto , Marchand, Loı̈c Le , Marmé, Frederik , Meindl, Alfons, Muir, Kenneth , Neuhausen, Susan L. , Nevanlinna, Heli , Nord, Silje , Olson, Janet E. , Rudolph, Anja , Toland, Amanda Ewart , Zamora, Pilar M. , Hooning, Maartje J. , Martens, John W.M. , Kristensen, Vessela N. , Hall, Per N , Pharoah, Paul D.P. , Cai, Qiuyin , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Teo, Soo H , Shrubsole, Martha J , Swerdlow, Anthony J , Southey, Melissa C , Matsuo, Keitaro , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Guénel, Pascal , Hartman, Mikael , Li, Jingmei , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Michailidou, Kyriaki , Bogdanova, Natalia V , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Kar, Siddhartha , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , Kang, Daehee , Droit, Arnaud
International Journal of Cancer | April 18, 2016 | Volume: 139 | Issue: 6 | Pages: 1303-1317
Previous genome‐wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine‐mapping study across 2.06 Mb (chr8:127,561,724–129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93–0.97, conditional p = 5.8 × 10−6), rs7815245 (OR = 0.94, 95% CI = 0.91–0.96, conditional p = 1.1 × 10−6) and rs2033101 (OR = 1.05, 95% CI = 1.02–1.07, conditional p = 1.1 × 10−4) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r2 = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.
Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk
Long, Jirong , Zeng, Chenjie , Michailidou, Kyriaki , Ghoussaini, Maya , Bolla, Manjeet K. , Wang, Qin, Shu, Xiao-Ou, Beesley, Jonathan, Kar, Siddhartha , Andrulis, Irene L. , Beckmann, Matthias W. , Beeghly‐Fadiel, Alicia, Benı́tez, Javier , Blot, William J. , Bogdanova, Natalia , Bojesen, Stig E. , Brauch, Hiltrud , Brenner, Hermann , Brinton, Louise A. , Brüning, Thomas , Burwinkel, Barbara , Cai, Hui , Canisius, Sander , Chang‐Claude, Jenny , Choi, Ji‐Yeob , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Darabi, Hatef, Devilee, Peter , Droit, Arnaud , Dörk, Thilo , Fasching, Peter A. , Fletcher, Olivia , Flyger, Henrik, Fostira, Florentia, Gaborieau, Valérie , García‐Closas, Montserrat , Giles, Graham G. , Grip, Mervi, Guénel, Pascal , Haiman, Christopher A., Hamann, Ute , Hartman, Mikael , Hollestelle, Antoinette , Hopper, John L. , Hsiung, Chia-Ni, Jakubowska, Anna , Johnson, Nichola , Kabisch, Maria, Kang, Daehee , Khan, Sofia , Knight, Julia A. , Kosma, Veli-Matti, Lambrechts, Diether , Li, Jingmei , Lindblom, Annika , Lubiński, Jan , Mannermaa, Arto, Manoukian, Siranoush , Margolin, Sara , Matsuo, Keitaro , McLean, Catriona , Meindl, Alfons , Muir, Kenneth , Orr, Nick , Peterlongo, Paolo , Putti, Thomas Choudary , Sangrajrang, Suleeporn , Sawyer, Elinor J. , Schmidt, Marjanka K. , Schmutzler, Rita K., Shrubsole, Martha J. , Southey, Melissa C. , Swerdlow, Anthony J. , Teo, Soo‐Hwang , Thienpont, Bernard , Tollenaar, Robert A.E.M., Tomlinson, Ian , Truong, Thérèse , Tseng, Chiu-Chen, Ouweland, Ans van den, Wen, Wanqing , Winqvist, Robert , Wu, Anna H. , Yip, Cheng Har , Zamora, M. Pilar , Zheng, Ying , Simard, Jacques , Chenevix‐Trench, Georgia , Investigators, on behalf of kConFab, Dunning, Alison M. , Easton, Douglas F. , Zheng, Wei , Wang, Sophia , Radice, Paolo , Webb, Penelope M. , Whiteman, David C. , Pepłońska, Beata , Durocher, Francine , Heikkinen, Tuomas , Balasubramanian, Sabapathy P. , DeFazio, Anna , Peissel, Bernard , Zaffaroni, Daniela , Hillemanns, Peter , Kerin, Michael J. , Pylkäs, Katri , Thorne, Heather , Cai, Hui , Laurent‐Puig, Pierre , Lambrechts, Diether , Taib, Nur Aishah Mohd , Colleran, Gabrielle , Fazio, Anna de , Guo, Xingyi , Wang, Qin, Milne, Roger L. , Cai, Qiuyin , Anton‐Culver, Hoda , Arndt, Volker , Beeghly‐Fadiel, Alicia , Broeks, Annegien , Couch, Fergus J. , Czene, Kamila , Ito, Hidemi , Marchand, Loı̈c Le , Lophatananon, Artitaya , Mannermaa, Arto, Marmé, Frederik , Meindl, Alfons , Neuhausen, Susan L. , Nevanlinna, Heli , Nord, Silje , Olson, Janet E. , Rudolph, Anja , Shen, Chen‐Yang , Shi, Jiajun , Toland, Amanda Ewart , Hall, Per N , Pharoah, Paul D.P. , Investigators, on behalf of kConFab, Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Teo, Soo H , Webb, Penelope M , Hillemanns, Peter , Shrubsole, Martha J , Swerdlow, Anthony J , Radice, Paolo , Southey, Melissa C , Muir, Kenneth , Matsuo, Keitaro , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , Hartman, Mikael , Li, Jingmei , García-Closas, Montserrat , Schmidt, Marjanka K , Michailidou, Kyriaki , Bogdanova, Natalia V , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Wang, Sophia S , Whiteman, David C , Kar, Siddhartha , Pylkäs, Katri , Laurent-Puig, Pierre , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Mohd Taib, Nur Aishah , Sawyer, Elinor J , Orr, Nick , Kang, Daehee , Droit, Arnaud
Cancer Epidemiology, Biomarkers & Prevention | September 10, 2015 | Volume: 24 | Issue: 11 | Pages: 1680-1691
Abstract Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1680–91. ©2015 AACR.