Citations 13
A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci
Rand, Kristin A. , Song, Chi , Déan, Eric, Serie, Daniel, Curtin, Karen , Sheng, Xin , Huff, Carol Ann , Bernal‐Mizrachi, Leon , Tomasson, Michael H. , Pawlish, Karen , Peters, Edward , Stram, Alex , Edlund, Christopher K., Conti, David V. , Zimmerman, Todd M., Hwang, Amie E. , Huntsman, Scott , Graff, John, Kong, Yinfei , Pregja, Silvana, Berndt, Sonja I. , Blot, William J. , Carpten, John D. , Chu, Lisa W., Diver, W. Ryan , Stevens, Victoria L. , Lieber, Michael R. , Goodman, Phyllis J. , Hennis, Anselm , Hsing, Ann W. , Mehta, Jayesh, Klein, Eric A. , Leske, Cristina, Murphy, Adam B. , Nemesure, Barbara , Strom, Sara S., Vij, Ravi , Rybicki, Benjamin A. , Stanford, Janet L. , Signorello, Lisa B., Witte, John S. , Bhatti, Parveen , Hu, Jennifer J. , Nyante, Sarah J. , Birmann, Brenda M. , Atanackovic, Djordje , Glenn, Martha, Jones, Brandt, Tricot, Guido , Kumar, Shaji , Wolf, Jeffrey L. , Halverson, Sandra L. , Rothman, Nathaniel , Brooks‐Wilson, Angela , Kolonel, Laurence N. , Severson, Richard K., Janakiraman, Nalini, Terebelo, Howard R. , Brown, Elizabeth E. , Roos, Anneclaire J. De , Mohrbacher, Ann , Spinelli, John J. , Munshi, Nikhil C. , Levy, Joan, Zonder, Jeffrey A. , Orlowski, Robert Z. , Camp, Nicola J. , Vachon, Celine M. , Ziv, Elad , Hazelett, Dennis J. , Haiman, Christopher A. , Serie, Daniel J, Hu, Donglei , Ailawadhi, Sikander , Singhal, Seema , Bock, Cathryn Hufford , Berg, David Van Den , Nooka, Ajay K. , Casey, Graham , Kittles, Rick A. , Kolb, Suzanne , Neslund-Dudas, Christine M , Ambrosone, Christine B. , John, Esther M. , Bernstein, Leslie , Zheng, Wei , Olshan, Andrew F. , Ziegler, Regina G. , Bandera, Elisa V. , Ingles, Sue A. , Press, Michael F. , Cannon‐Albright, Lisa , Martin, Thomas G. , Rothman, Nathaniel , Rajkumar, S. Vincent , Chanock, Stephen Jacob , Slager, Susan L. , Colditz, Graham A. , Giles, Graham G. , Chiu, Brian C.‐H. , Anderson, Kenneth C. , Orlowski, Robert Z. , Lonial, Sagar , Vachon, Celine M. , Stram, Daniel O. , Cozen, Wendy , Hazelett, Dennis J , Brooks-Wilson, Angela R , Klein, Eric A , De Roos, Anneclaire J , Nyante, Sarah , Bhatti, Parveen , Birmann, Brenda M , Ziv, Elad , Conti, David V
Cancer Epidemiology, Biomarkers & Prevention | September 2, 2016 | Volume: 25 | Issue: 12 | Pages: 1609-1618
Abstract Background: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. Methods: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. Results: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry–European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4. Correlated variants in 7p15.3 clustered around an enhancer at the 3′ end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10−7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7. Conclusions: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. Impact: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609–18. ©2016 AACR.
Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations
Fehringer, Gordon , Kraft, Peter , Eeles, Rosalind A. , Chatterjee, Nilanjan , Schumacher, Fredrick R. , Schildkraut, Joellen M. , Lindström, Sara , Brennan, Paul , Bickeböller, Heike , Houlston, Richard S. , Landi, Maria Teresa , Caporaso, Neil E. , Risch, Angela , Olama, Ali Amin Al , Berndt, Sonja I. , Giovannucci, Edward L. , Grönberg, Henrik , Muir, Kenneth , Stampfer, Meir J. , Stevens, Victoria L. , Goode, Ellen L. , Reid, Brett M. , Brenner, Hermann , Chang‐Claude, Jenny , Kocarnik, Jonathan K., Slattery, Martha L. , Adank, Muriel A. , Ahsan, Habibul , Aittomäki, Kristiina, Baglietto, Laura , Blomquist, Carl, Canzian, Federico , Eliassen, A. Heather , Figueroa, Jonine D. , Flesch‐Janys, Dieter, Fletcher, Olivia , García‐Closas, Montserrat , Gaudet, Mia M. , Johnson, Nichola , Hazra, Aditi , Hein, Rebecca, Hofman, Albert , Irwanto, Astrid , Johansson, Mattias , Lichtner, Peter , Liu, Jianjun , Lund, Eiliv , Makalic, Enes , Meindl, Alfons , Müller‐Myhsok, Bertram , Muranen, Taru , Peeters, Petra H., Peto, Julian, Prentice, Ross L. , Sánchez, María‐José , Schmutzler, Rita K. , Southey, Melissa C. , Travis, Ruth C. , Turnbull, Clare , Uitterlinden, André G. , Wang, Zhaoming , Whittemore, Alice S. , Yang, Xiaohong R. , Zheng, Wei , Buchanan, Daniel D. , Casey, Graham , Conti, David V. , Edlund, Christopher K., Gallinger, Steven , Haile, Robert W. , Jenkins, Mark A. , Li, Li , Lindor, Noralene M., Schmit, Stephanie L. , Thibodeau, Stephen N. , Woods, Michael O. , Rafnar, Þórunn , Guðmundsson, Jūlı́us, Stacey, Simon , Stefánsson, Kāri , Sulem, Patrick , Chen, Y. Ann , Wei, Yongyue , Shen, Hongbing , Hu, Zhibin , Obeidat, Ma’en , Nickle, David C. , Timens, Wim , Freedman, Matthew L. , Seminara, Daniela, Gong, Jian , Peters, Ulrike , Gruber, Stephen B. , Sellers, Thomas A. , Easton, Douglas F. , Hunter, David J. , Haiman, Christopher A. , Henderson, Brian E., Hung, Rayjean J., Batra, Jyotsna , Hung, Rayjean J. , Pharoah, Paul D.P. , Kote‐Jarai, Zsofia , Ma, Jing , Wiklund, Fredrik E. , Willett, Walter C. , Permuth, Jennifer B. , Risch, Harvey A. , Bezieau, Stéphane , Chan, Andrew T. , Hudson, Thomas J , Newcomb, Polly A. , Schoen, Robert E. , White, Emily E. , Czene, Kamila , dos‐Santos‐Silva, Isabel , Hall, Per N , Hopper, John L. , Kaaks, Rudolf , Kibriya, Muhammad Ghulam , Meindl, Alfons , Nevanlinna, Heli , Rahman, Nazneen , Schmidt, Daniel F. , Tamimi, Rulla M. , Marchand, Loı̈c Le , Tyrer, Jonathan P. , Christiani, David C. , Shu, Xiao‐Ou , Shiraishi, Kouya , Takahashi, Atsushi , Bossé, Yohan , Li, Qiyuan , Chanock, Stephen Jacob , Amos, Christopher I. , Hung, Rayjean J., Buchanan, Daniel D , Houlston, Richard S , Eeles, Rosalind A , Southey, Melissa C , Jenkins, Mark A , Canzian, Federico , Hung, Rayjean J , Muir, Kenneth , Travis, Ruth C , Haile, Robert W , Wang, Zhaoming , Brenner, Hermann , Muranen, Taru A , García-Closas, Montserrat , Makalic, Enes , Kraft, Peter , Zheng, Wei , Figueroa, Jonine D , Eliassen, A Heather , Conti, David V , Batra, Jyotsna , Johansson, Mattias , Baglietto, Laura , Fletcher, Olivia , Sánchez, Maria-Jose , Risch, Angela , Bickeböller, Heike , Shen, Hongbing , Timens, Wim , Liu, Jing
Cancer Research | April 21, 2016 | Volume: 76 | Issue: 17 | Pages: 5103-5114
Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.
Genome-Wide Association Study of Prostate Cancer–Specific Survival
Szulkin, Robert , Whitington, Thomas, Aly, Markus , Grönberg, Henrik , Eeles, Rosalind A. , Easton, Douglas F. , Olama, Ali Amin Al , Benlloch, Sara, Muir, Kenneth , Giles, Graham G. , Southey, Melissa C. , FitzGerald, Liesel M. , Henderson, Brian E., Schumacher, Fredrick R. , Haiman, Christopher A. , Sipeky, Csilla , Tammela, Teuvo L.J. , Nordestgaard, Børge G. , Travis, Ruth C. , Neal, David E. , Donovan, Jenny , Hamdy, Freddie C. , Pashayan, Nora , Stanford, Janet L. , Thibodeau, Stephen N. , McDonnell, Shannon K. , Schaid, Daniel J. , Maier, Christiane, Vogel, Walther , Luedeke, Manuel, Herkommer, Kathleen , Kibel, Adam S. , Lubiński, Jan , Kluźniak, Wojciech , Cannon‐Albright, Lisa , Brenner, Hermann , Herrmann, Volker, Holleczek, Bernd , Sellers, Thomas A. , Lim, Hui-Yi, Kaneva, Radka , Mitev, Vanio , Teixeira, Manuel R. , Paulo, Paula , Maia, Sofia , Pandha, Hardev , Michael, Agnieszka , Batra, Jyotsna , Clements, Judith A. , BioResource, on behalf of the Australian Prostate Cancer, Albanes, Demetrius, Andriole, Gerald L. , Berndt, Sonja I., Gapstur, Susan M. , Giovannucci, Edward L. , Ma, Jing , Mondul, Alison M. , Stampfer, Meir J. , Stevens, Victoria L. , Weinstein, Stephanie J. , Trichopoulou, Antonia , Bueno-de-Mesquita, Bas H., Tjønneland, Anne , Cox, David G. , Mæhle, Lovise, Schleutker, Johanna , Lindström, Sara , Karlsson, Robert , Kote‐Jarai, Zsofia , Key, Tim , Pharoah, Paul D.P. , Khaw, Kay‐Tee , Cybulski, Cezary , Park, Jong Y. , Slavov, Chavdar , Spurdle, Amanda B. , Kierzek, Andrzej , BioResource, on behalf of the Australian Prostate Cancer, Berndt, Sonja I. , Chanock, Stephen Jacob , Hunter, David J. , Kraft, Peter , Marchand, Loı̈c Le , Penney, Kathryn , Wiklund, Fredrik E. , Giles, Graham G , Teixeira, Manuel R , Eeles, Rosalind A , Southey, Melissa C , Tjønneland, Anne , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Cannon-Albright, Lisa A , Michael, Agnieszka , Brenner, Hermann , Batra, Jyotsna , Clements, Judith , Lubinski, Jan , McDonnell, Shannon K
Cancer Epidemiology, Biomarkers & Prevention | August 25, 2015 | Volume: 24 | Issue: 11 | Pages: 1796-1800
Abstract Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev; 24(11); 1796–800. ©2015 AACR.