Citations 26
Integration of Population-Level Genotype Data with Functional Annotation Reveals Over-Representation of Long Noncoding RNAs at Ovarian Cancer Susceptibility Loci
Reid, Brett M. , Teer, Jamie K. , Monteiro, Álvaro N.A. , Chen, Zhihua , Chenevix‐Trench, Georgia , Goode, Ellen L. , Iverson, Edwin S., Lawrenson, Kate , Pearce, Celeste Leigh , Phelan, Catherine M., Ramus, Susan J. , Rossing, Mary Anne, Schildkraut, Joellen M. , Cheng, Jin Q. , Gayther, Simon A. , Sellers, Thomas A. , Bowtell, David D.L. , Permuth, Jennifer B. , Chen, Y. Ann , Tyrer, Jonathan P. , Berchuck, Andrew , Doherty, Jennifer A. , Pharoah, Paul D.P. , Ramus, Susan J , Lawrenson, Kate , Monteiro, Alvaro N , Chenevix-Trench, Georgia , Bowtell, David D
Cancer Epidemiology, Biomarkers & Prevention | December 29, 2016 | Volume: 26 | Issue: 1 | Pages: 116-125
Abstract Background: Genome-wide association studies (GWAS) have identified multiple loci associated with epithelial ovarian cancer (EOC) susceptibility, but further progress requires integration of epidemiology and biology to illuminate true risk loci below genome-wide significance levels (P < 5 × 10−8). Most risk SNPs lie within non–protein-encoding regions, and we hypothesize that long noncoding RNA (lncRNA) genes are enriched at EOC risk regions and represent biologically relevant functional targets. Methods: Using imputed GWAS data from about 18,000 invasive EOC cases and 34,000 controls of European ancestry, the GENCODE (v19) lncRNA database was used to annotate SNPs from 13,442 lncRNAs for permutation-based enrichment analysis. Tumor expression quantitative trait locus (eQTL) analysis was performed for sub-genome-wide regions (1 × 10−5 > P > 5 × 10−8) overlapping lncRNAs. Results: Of 5,294 EOC-associated SNPs (P < 1.0 × 10−5), 1,464 (28%) mapped within 53 unique lncRNAs and an additional 3,484 (66%) SNPs were correlated (r2 > 0.2) with SNPs within 115 lncRNAs. EOC-associated SNPs comprised 130 independent regions, of which 72 (55%) overlapped with lncRNAs, representing a significant enrichment (P = 5.0 × 10−4) that was more pronounced among a subset of 5,401 lncRNAs with active epigenetic regulation in normal ovarian tissue. EOC-associated lncRNAs and their putative promoters and transcription factors were enriched for biologically relevant pathways and eQTL analysis identified five novel putative risk regions with allele-specific effects on lncRNA gene expression. Conclusions: lncRNAs are significantly enriched at EOC risk regions, suggesting a mechanistic role for lncRNAs in driving predisposition to EOC. Impact: lncRNAs represent key candidates for integrative epidemiologic and functional studies. Further research on their biologic role in ovarian cancer is indicated. Cancer Epidemiol Biomarkers Prev; 26(1); 116–25. ©2016 AACR.
PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
Southey, Melissa C. , Goldgar, David E, Winqvist, Robert , Pylkäs, Katri , Michailidou, Kyriaki , Rensburg, Elizabeth J. van , Heikkinen, Tuomas , Hopper, John L. , Dörk, Thilo , Claes, Kathleen , Teo, Zhi L. , Radice, Paolo , Catucci, Irene, Peterlongo, Paolo , Odefrey, Fabrice, Dowty, James G., Schmidt, Marjanka K. , Hogervorst, Frans B.L., Verhoef, Senno, Carpenter, Jane, Clarke, Christine L. , Scott, Rodney J. , Fasching, Peter A. , Haeberle, Lothar, Ekici, Arif B. , Beckmann, Matthias W. , Peto, Julian , Fletcher, Olivia , Johnson, Nichola , Bolla, Manjeet K. , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Marmé, F., Burwinkel, Barbara , Guénel, Pascal , Truong, Thérèse , Sanchez, Marie, Bojesen, Stig E. , Nielsen, Sune F. , Flyger, Henrik, Benı́tez, Javier , Zamora, M. Pilar , Menéndez, Primitiva, Brenner, Hermann , Stegmaier, Christa, Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Muranen, Taru , Aittomäki, Kristiina, Blomqvist, Carl , Bogdanova, Natalia , Antonenkova, Natalia, Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wauters, Els , Smeets, Dominiek, Beuselinck, Benoit , Floris, Giuseppe , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Vachon, Celine M. , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Kristensen, Vessela, Alnæs, Grethe Grenaker, Zheng, Wei , Hunter, David J. , Lindström, Sara, Hankinson, Susan E. , Kraft, Peter , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Jukkola‐Vuorinen, Arja , Grip, Mervi, Kauppila, Saila , Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, García‐Closas, Montserrat , Figueroa, Jonine D. , Lissowska, Jolanta , Darabi, Hatef, Eriksson, Mikael , Eccles, Diana M, Tapper, William , Gerty, Sue, Hooning, Maartje J. , Collée, J. Margriet, Tilanus‐Linthorst, Madeleine M.A., Li, Jingmei , Brand, Judith S. , Humphreys, Keith , Reed, Malcolm , Luccarini, Craig , Baynes, Caroline, Dunning, Alison M. , Hamann, Ute, Torres, Diana , Ulmer, Hans Ulrich, Rüdiger, Thomas , Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Slager, Susan, Yannoukakos, Drakoulis , Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nick , Jones, Michael E. , González‐Neira, Anna , Pita, Guillermo , Alonso, M. Rosario, Álvarez, Núria, Herrero, Daniel, Tessier, Daniel C., Vincent, Daniel , Bacot, François, Simard, Jacques , Dumont, Martine , Soucy, Penny, Eeles, Rosalind A. , Muir, Kenneth , Grönberg, Henrik , Schleutker, Johanna , Nordestgaard, Børge G. , Weischer, Maren , Travis, Ruth C. , Neal, David E. , Donovan, Jenny , Hamdy, Freddie C. , Stanford, Janet L. , Blot, William J. , Thibodeau, Stephen N. , Schaid, Daniel J. , Kelley, Joseph L., Maier, Christiane, Kibel, Adam S. , Butterbach, Katja, Kaneva, Radka , Batra, Jyotsna , Teixeira, Manuel R. , Olama, Ali Amin Al , Benlloch, Sara, Hartmann, Arndt , Hein, Alexander , Ruebner, Matthias , Lambrechts, Diether , Nieuwenhuysen, Els Van , Vergote, Ignace , Lambretchs, Sandrina, Rossing, Mary Anne, Nickels, Stefan , Eilber, Ursula, Wang‐Gohrke, Shan , Odunsi, Kunle , Sucheston‐Campbell, Lara, Friel, Grace , Lurie, Galina, Killeen, Jeffrey , Goodman, Marc T. , Runnebaum, Ingo B., Hillemanns, Peter , Pelttari, Liisa M. , Edwards, Robert P., Ness, Roberta B., Moysich, Kirsten B., Heitz, Florian , Harter, Philipp , Kommoss, Stefan , Walsh, Christine , Lester, Jenny, Jensen, Allan , Høgdall, Estrid , Peissel, Bernard , Bernard, Loris, Goode, Ellen L. , Vierkant, Robert A. , Cunningham, Julie M. , Fogarty, Zachary C. , Kalli, Kimberly R., Liang, Dong , Lu, Karen H., Hildebrandt, Michelle A.T., Wu, Xifeng , Levine, Douglas A. , Bisogna, Maria, Iversen, Edwin S., Marks, Jeffrey R. , Akushevich, Lucy , Schildkraut, Joellen M. , Terry, Kathryn L. , Stampfer, Meir J. , Tworoger, Shelley S. , Olson, Sara H. , Salvesen, Helga B., Altena, Anne M. van , Aben, Katja K.H. , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Bean, Yukie T., Kelemen, Linda E., Le, Nhu D. , Górski, Bohdan , Menkiszak, Janusz , Høgdall, Claus , Lundvall, Lene, Nedergaard, Lotte , Engelholm, Svend Aage, Dicks, Ed , Campbell, Ian , McNeish, Iain A. , Whittemore, Alice S. , Rothstein, Joseph H. , McGuire, Valerie, Sieh, Weiva , Cai, Hui , Teten, Rachel Threet, Sutphen, Rebecca , McLaughlin, John R, Narod, Steven A., Phelan, Catherine M., Monteiro, Álvaro N.A. , Fenstermacher, David, Lin, Hui‐Yi , Sellers, Thomas A. , Chen, Y. Ann , Chen, Zhihua , Gayther, Simon A. , Ramus, Susan J. , Menon, Usha , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Moes-Sosnowska, Joanna , Kupryjańczyk, Jolanta , Song, Honglin , Winship, Ingrid , Chenevix‐Trench, Georgia , Tavtigian, Sean V. , Easton, Doug , Lu, Karen H. , Durocher, Francine , Eccles, Diana , Lambrechts, Diether , Vachon, Celine, Pankratz, Vernon S, Thibodeau, Stephen, Goldgar, David E, Couch, Fergus J. , Tischkowitz, Marc D. , Foulkes, William D. , Dennis, Joe , Nevanlinna, Heli , Reis‐Filho, Jorge S. , Tsimiklis, Helen , Broeks, Annegien , dos‐Santos‐Silva, Isabel , Yang, Rongxi , Ménégaux, F. , Sanchez, Marie, Pérez, José Ignacio Arias , Anton‐Culver, Hoda , Neuhausen, Susan L. , Ziogas, Argyrios , Clarke, Christina A. , Arndt, Volker , Mannermaa, Arto, Spurdle, Amanda B. , Group, Australian Ovarian Cancer Study, Rudolph, Anja , Seibold, Petra , Olson, Janet E. , Vachon, Celine M. , Pankratz, V. Shane , Marchand, Loı̈c Le , Kristensen, Vessela N. , Hankinson, Susan E. , Hollestelle, Antoinette , Chanock, Stephen Jacob , Czene, Kamila , Eriksson, Mikael , Eccles, Diana M, Rafiq, Sajjad , Hooning, Maartje J. , Martens, John W.M. , Hall, Per N , Cox, Angela , Toland, Amanda Ewart , Ambrosone, Christine B. , Wiklund, Fredrik E. , Khaw, Kay‐Tee , Cybulski, Cezary , Cannon‐Albright, Lisa , Park, Jong, Kote‐Jarai, Zsofia , Renner, Stefan P. , Doherty, Jennifer A. , Wilkens, Lynne R. , Bützow, Ralf C. , Modugno, Francesmary , Moysich, Kirsten B., Bois, Andreas du , Karlan, Beth Y. , Kjær, Susanne K. , Bonanni, Bernardo , Fridley, Brooke L. , Larson, Melissa C. , Hildebrandt, Michelle A.T. , Dao, Fanny , Berchuck, Andrew , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Orlow, Irene , Bjørge, Line , Pejovic, Tanja B. , Brooks‐Wilson, Angela , Cook, Linda S. , Gronwald, Jacek , Tyrer, Jonathan P. , Paul, James , Siddiqui, Nadeem , Glasspool, Rosalind , Shu, Xiao‐Ou , McLaughlin, John R, Permuth, Jennifer B. , Gentry‐Maharaj, Aleksandra , Berg, David Van Den , Pharoah, Paul D.P. , Giles, Graham G. , Milne, Roger L. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Tworoger, Shelley S , van Rensburg, Elizabeth J , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Radice, Paolo , Lissowska, Jolanta , Claes, Kathleen B M , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Menkiszak, Janusz , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Lin, Hui-Yi , Fogarty, Zachary C , Dunning, Alison M , Heitz, Florian , Jakubowska, Anna , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , Li, Jingmei , Muranen, Taru A , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Winship, Ingrid M , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Batra, Jyotsna , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Goodman, Marc T , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Journal of Medical Genetics | September 5, 2016 | Volume: 53 | Issue: 12 | Pages: 800-811
Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility: results from a large-scale collaboration
Group, AOCS Study, Reid, Brett M. , Earp, Madalene A. , Chen, Y. Ann , Monteiro, Álvaro N.A. , Chen, Zhihua , Chenevix‐Trench, Georgia , Fasching, Peter A. , Beckmann, Matthias W. , Lambrechts, Diether , Vanderstichele, Adriaan , Niewenhuyse, Els Van, Vergote, Ignace , Rossing, Mary Anne, Chang‐Claude, Jenny, Moysich, Kirsten, Odunsi, Kunle , Goodman, Marc T. , Shvetsov, Yurii B. , Thompson, Pamela J., Dörk, Thilo , Bogdanova, Natalia , Pelttari, Liisa M. , Leminen, Arto, Edwards, Robert P., Ness, Roberta B., Kelley, Joseph L., Lester, Jenny, Jensen, Allan , Hildebrandt, Michelle, Liang, Dong , Lu, Karen H., Wu, Xifeng , Levine, Douglas A. , Bisogna, Maria, Berchuck, Andrew, Terry, Kathryn L. , Tworoger, Shelley S. , Cunningham, Julie M. , Winham, Stacey J. , Olson, Sara H. , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Moffitt, Melissa , Le, Nhu, Kelemen, Linda E. , Lubiński, Jan , Wentzensen, Nicolas, Brinton, Louise A. , Lissowska, Jolanta , Yang, Hanna , Høgdall, Estrid , Høgdall, Claus , Lundvall, Lene, Song, Honglin , Campbell, Ian , Eccles, Diana , McNeish, Iain A. , Whittemore, Alice S. , McGuire, Valerie, Sieh, Weiva , Rothstein, Joseph H. , Phelan, Catherine M., Narod, Steven A., McLaughlin, John, Ziogas, Argyrios, Menon, Usha , Gayther, Simon A. , Ramus, Susan J. , Pearce, Celeste Leigh, Wu, Anna H. , Kupryjańczyk, Jolanta , Dansonka‐Mieszkowska, Agnieszka , Schildkraut, Joellen M. , Cheng, Jin Q. , Goode, Ellen L. , Sellers, Thomas A. , Lu, Karen H. , Lambrechts, Diether , Earp, Madalene, Cunningham, Julie, Permuth, Jennifer B. , Group, AOCS Study, Doherty, Jennifer A. , Wilkens, Lynne R. , Bützow, Ralf C. , Nevanlinna, Heli , Modugno, Francesmary , Heitz, Florian , Karlan, Beth Y. , Lester, Jenny, Kjær, Susanne K. , Giles, Graham G. , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Fridley, Brooke L. , Orlow, Irene , Bjørge, Line , Pejovic, Tanja B. , Cook, Linda S. , Brooks‐Wilson, Angela , Gronwald, Jacek , Wentzensen, Nicolas , Pharoah, Paul D.P. , Risch, Harvey A. , McLaughlin, John, Anton‐Culver, Hoda , Gentry‐Maharaj, Aleksandra , Pelttari, L M , Winham, Stacey J , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Ramus, Susan J , Tworoger, Shelley S , Vanderstichele, Adriaan , Jensen, Allan , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Moysich, Kirsten , Lissowska, Jolanta , Campbell, Ian G , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T
Oncotarget | July 28, 2016 | Volume: 7 | Issue: 45 | Pages: 72381-72394
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
Kar, Siddhartha , Beesley, Jonathan, Olama, Ali Amin Al , Michailidou, Kyriaki , Lawrenson, Kate , Lindström, Sara, Ramus, Susan J. , Thompson, Deborah J. , Investigators, ABCTB, Kibel, Adam S. , Dansonka‐Mieszkowska, Agnieszka , Michael, Agnieszka , Dieffenbach, Aida Karina, Whittemore, Alice S. , Monteiro, Álvaro N.A. , Peixoto, Ana , González‐Neira, Anna , Wu, Anna H. , Lindblom, Annika , Swerdlow, Anthony J. , Cancer), AOCS Study Group & Australian Cancer Study (Ovarian, BioResource, APCB, Ekici, Arif B. , Burwinkel, Barbara , Nordestgaard, Børge G. , Blomqvist, Carl , Phelan, Catherine, McLean, Catriona , Pearce, Celeste Leigh, Vachon, Celine M. , Stegmaier, Christa, Maier, Christiane, Høgdall, Claus , Kang, Daehee , Tessier, Daniel C., Schaid, Daniel J. , Neal, David E. , Eccles, Diana , Flesch‐Janys, Dieter, Wokozorczyk, Dominika, Levine, Douglas A. , Yannoukakos, Drakoulis , Sawyer, Elinor J. , Goode, Ellen L. , Хуснутдинова, Э. К. , Høgdall, Estrid , Song, Fengju, Bruinsma, Fiona, Heitz, Florian , Hamdy, Freddie C. , Olsson, Håkan , Wildiers, Hans , Ulmer, Hans-Ulrich, Pandha, Hardev , Darabi, Hatef, Salvesen, Helga B., Grönberg, Henrik , Brenner, Hermann , Brauch, Hiltrud , Song, Honglin , Lim, Hui-Yi, McNeish, Iain A. , Campbell, Ian , Vergote, Ignace , Lubiński, Jan , Stanford, Janet L. , Benı́tez, Javier , Chang‐Claude, Jenny , Donovan, Jenny , Schildkraut, Joellen M. , Schleutker, Johanna , Hopper, John L. , Kupryjańczyk, Jolanta , Figueroa, Jonine D. , Clements, Judith A. , Knight, Julia A. , Peto, Julian , Cunningham, Julie M. , Pow‐Sang, Julio M. , Batra, Jyotsna , Lu, Karen H., Herkommer, Kathleen , Investigators, kConFab, Matsuo, Keitaro , Muir, Kenneth , Offitt, Kenneth, Chen, Kexin , Moysich, Kirsten B., Aittomäki, Kristiina, Odunsi, Kunle , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Hooning, Maartje J. , Pike, Malcolm C., Bolla, Manjeet K. , Luedeke, Manuel, Teixeira, Manuel R. , Goodman, Marc T. , Schmidt, Marjanka K. , Riggan, Marjorie J. , Rossing, Mary Anne, Beckmann, Matthias W. , Moisse, Matthieu , Southey, Melissa C. , Jones, Michael E. , Hildebrandt, Michelle A.T., Hou, Ming‐Feng , Schoemaker, Minouk J. , García‐Closas, Montserrat , Bogdanova, Natalia , Investigators, NBCS, Le, Nhu D. , Orr, Nick , Wentzensen, Nicolas , Pashayan, Nora , Peterlongo, Paolo , Guénel, Pascal , Brennan, Paul , Paulo, Paula , Webb, Penelope M. , Broberg, Per, Fasching, Peter A. , Devilee, Peter , Wang, Qin, Kaneva, Radka , Kopperud, Reidun Kristin, Schmutzler, Rita K., Stephenson, Robert A., MacInnis, Robert J. , Hoover, Robert N. , Winqvist, Robert , Ness, Roberta B., Travis, Ruth C. , Benlloch, Sara, Olson, Sara H. , McDonnell, Shannon K. , Tworoger, Shelley S. , Maia, Sofia , Berndt, Sonja I., Lee, Soo Chin , Teo, Soo‐Hwang , Thibodeau, Stephen N. , Bojesen, Stig E. , Gapstur, Susan M. , Tammela, Teuvo L.J. , Network, the GENICA, Dörk, Thilo , Brüning, Thomas , Wahlfors, Tiina , Edwards, Todd L., Menon, Usha , Hamann, Ute , Mitev, Vanio , Kosma, Veli‐Matti , Setiawan, Veronica Wendy , Kristensen, Vessela, Vogel, Walther , Zheng, Wei , Sieh, Weiva , Blot, William J. , Kluźniak, Wojciech , Gao, Yu‐Tang , Schumacher, Fredrick R. , Freedman, Matthew L., Dunning, Alison M. , Simard, Jacques , Haiman, Christopher A. , Sellers, Thomas A. , Hunter, David J. , Henderson, Brian E., Kraft, Peter , Gayther, Simon A. , Easton, Douglas F. , Chenevix‐Trench, Georgia , Eeles, Rosalind A. , Lambrechts, Diether , Lu, Karen H. , Durocher, Francine , Zheng, Wei , Thorne, Heather , Lambrechts, Diether , Chen, Kexin , Vachon, Celine, Tyrer, Jonathan P. , Kote‐Jarai, Zsofia , Investigators, ABCTB, Gentry‐Maharaj, Aleksandra , Wolk, Alicja , Kierzek, Andrzej , Cox, Angela , Rudolph, Anja , Cancer), AOCS Study Group & Australian Cancer Study (Ovarian, BioResource, APCB, Ziogas, Argyrios , Karlan, Beth Y. , Vachon, Celine M. , Cybulski, Cezary , Slavov, Chavdar , Ambrosone, Christine B. , Teerlink, Craig C. , Stram, Daniel O. , Cramer, Daniel W. , Edwards, Digna R. Velez , Bandera, Elisa V. , Poole, Elizabeth M. , Song, Fengju , Modugno, Francesmary , Wiklund, Fredrik E. , Giles, Graham G. , Risch, Harvey A. , Nevanlinna, Heli , Anton‐Culver, Hoda , Gronwald, Jacek , Doherty, Jennifer A. , Permuth, Jennifer B. , Dennis, Joe , Park, Jong Y. , Czene, Kamila , Khaw, Kay‐Tee , Investigators, kConFab, Moysich, Kirsten B., FitzGerald, Liesel M. , Cook, Linda S. , Cannon‐Albright, Lisa , Hooning, Maartje J. , Aly, Markus , Sanderson, Maureen , Lush, Michael J. , Hildebrandt, Michelle A.T. , Rahman, Nazneen , Investigators, NBCS, Wang, Qin, Cai, Qiuyin , Li, Qiyuan , Bützow, Ralf C. , Milne, Roger L. , Berndt, Sonja I. , Kjær, Susanne K. , Pejovic, Tanja B. , Network, the GENICA, Key, Tim , Kristensen, Vessela N. , Arndt, Volker , Shu, Xiao‐Ou , Berchuck, Andrew , Spurdle, Amanda B. , Chanock, Stephen Jacob , Couch, Fergus J. , Hall, Per N , Pharoah, Paul D.P. , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , Tworoger, Shelley S , Webb, Penelope M , Eccles, Diana , Menon, Usha , Lawrenson, Kate , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Michael, Agnieszka , Maclnnis, Robert , Matsuo, Keitaro , Dunning, Alison M , Heitz, Florian , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , García-Closas, Montserrat , Schmidt, Marjanka K , Ekici, Arif B , Moisse, Matthieu , Michailidou, Kyriaki , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Kar, Siddhartha , Batra, Jyotsna , Clements, Judith , Setiawan, Veronica W , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Bojesen, Stig E , Schoemaker, Minouk J , Goodman, Marc T , Wildiers, Hans , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , McDonnell, Shannon K , Kang, Daehee
Cancer Discovery | July 18, 2016 | Volume: 6 | Issue: 9 | Pages: 1052-1067
Abstract Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type–specific expression quantitative trait locus and enhancer–gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. Significance: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052–67. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 932
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.
A targeted genetic association study of epithelial ovarian cancer susceptibility
Earp, Madalene A. , Winham, Stacey J. , Sicotte, Hugues , Chien, Jeremy , Goodman, Marc T. , Levine, Douglas A. , Monteiro, Álvaro N.A. , Ness, Roberta B., Pearce, Celeste Leigh, Rossing, Mary Anne, Tworoger, Shelley S. , Wentzensen, Nicolas , Bisogna, Maria, Brinton, Louise A. , Brooks‐Wilson, Angela , Carney, Michael E. , Cunningham, Julie M. , Edwards, Robert P., Fogarty, Zachary C. , Iversen, Edwin S., Kraft, Peter , Le, Nhu D. , Lin, Hui‐Yi , Lissowska, Jolanta , Moysich, Kirsten B. , Olson, Sara H. , Pike, Malcolm C. , Rider, David N., Terry, Kathryn L. , Thompson, Pamela J., Vierkant, Robert A. , Vitonis, Allison F., Wu, Anna H. , Phelan, Catherine M., Schildkraut, Joellen M. , Chen, Y. Ann , Sellers, Thomas A. , Goode, Ellen L. , Earp, Madalene, Larson, Nicholas, Larson, Nicholas B. , Permuth, Jennifer B. , Anton‐Culver, Hoda , Bandera, Elisa V. , Berchuck, Andrew , Cook, Linda S. , Cramer, Daniel W. , Doherty, Jennifer A. , Larson, Melissa C. , Modugno, Francesmary , Poole, Elizabeth M. , Berg, David Van Den , Wilkens, Lynne R. , Yang, Hannah , Ziogas, Argyrios , Fridley, Brooke L. , Winham, Stacey J , Tworoger, Shelley S , Vierkant, Robert A , Chien, Jeremey , Monteiro, Alvaro N , Moysich, Kirsten , Lissowska, Jolanta , Brooks-Wilson, Angela R , Lin, Hui-Yi , Fogarty, Zachary C , Kraft, Peter , Goodman, Marc T
Oncotarget | February 2, 2016 | Volume: 7 | Issue: 7 | Pages: 7381-7389