Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations: Cancer Research

G. Fehringer, P. Kraft, Paul D. P. Pharoah, Rosalind A. Eeles, N. Chatterjee, Fredrick R. Schumacher, Joellen M. Schildkraut, S. Lindstrom, P. Brennan, H. Bickeboller, Richard S. Houlston, M.T. Landi, N. Caporaso, A. Risch, A. A. Al Olama, Sonja I Berndt, E.L. Giovannucci, H. Gronberg, Zsofia Kote-Jarai, Jun Ma & 118 others K. Muir, M. J. Stampfer, V.L. Stevens, Fredrik Wiklund, W.C. Willett, Ellen L. Goode, J. B. Permuth, Harvey A. Risch, B. M. Reid, S. Bezieau, H. Brenner, T.A. Chan, J. Chang-Claude, T.J. Hudson, J. K. Kocarnik, Polly A. Newcomb, R.E. Schoen, M. L. Slattery, E. White, M. A. Adank, H. Ahsan, K. Aittomaki, L. Baglietto, C. Blomquist, F. Canzian, K. Czene, I. dos Santos Silva, A. H. Eliassen, J.D. Figueroa, D. Flesch-Janys, O. Fletcher, M. Garcia-Closas, M. Gaudet, N. Johnson, P. Hall, A. Hazra, R. Hein, A. Hofman, John L. Hopper, A. Irwanto, M. Johansson, R. Kaaks, M.G. Kibriya, P. Lichtner, J. Liu, E. Lund, E. Makalic, A. Meindl, B. Muller-Myhsok, Taru A. Muranen, H. Nevanlinna, Petra H. Peeters, J. Peto, R. L. Prentice, N. Rahman, Anthony M. J. Sanchez, Daniel F. Schmidt, Rita K. Schmutzler, Melissa C. Southey, R. Tamimi, R.C. Travis, C. Turnbull, A. G. Uitterlinden, M. -Z. Wang, Alice S. Whittemore, X. H. R. Yang, W. Zheng, D. D. Buchanan, G. Casey, David V. Conti, Christopher K. Edlund, S. Gallinger, R. W. Haile, M. Jenkins, L. Le Marchand, L. Li, N.M. Lindor, S. L. Schmit, S. N. Thibodeau, M. O. Woods, T. Rafnar, J. Gudmundsson, S.N. Stacey, K. Stefansson, P. Sulem, A.Y. Chen, Jonathan P Tyrer, David C. Christiani, Y. Wei, H. B. Shen, Z. B. Hu, X.O. Shu, K. Shiraishi, A. Takahashi, Y. Bosse, M. Obeidat, D. Nickle, W. Timens, Matthew L. Freedman, Y.Q. Li, D. Seminara, Stephen J Chanock, J. Gong, U. Peters, Stephen B. Gruber, Christopher I. Amos, Thomas A. Sellers, Douglas F. Easton, David J. Hunter, Christopher A. Haiman, B.E. Henderson, Rayjean J. Hung, Ocac [Unknown], Practical Consortium, Res Hereditary Breast Ovarian Canc, Transdisciplinary Colorectal, Canc African Amer Breast, Canc African Ancestry Prostate

Research output: Contribution to journalArticleAcademicpeer-review

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 atCDKN2B-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. (C) 2016 AACR.
Original languageEnglish
Pages (from-to)5103-5114
Number of pages12
JournalCancer Research
Volume76
DOIs
Publication statusPublished - 2016

Cite this

Fehringer, G., Kraft, P., Pharoah, P. D. P., Eeles, R. A., Chatterjee, N., Schumacher, F. R., ... African Ancestry Prostate, C. (2016). Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations: Cancer Research. Cancer Research, 76, 5103-5114. https://doi.org/10.1158/0008-5472.can-15-2980
Fehringer, G. ; Kraft, P. ; Pharoah, Paul D. P. ; Eeles, Rosalind A. ; Chatterjee, N. ; Schumacher, Fredrick R. ; Schildkraut, Joellen M. ; Lindstrom, S. ; Brennan, P. ; Bickeboller, H. ; Houlston, Richard S. ; Landi, M.T. ; Caporaso, N. ; Risch, A. ; Al Olama, A. A. ; Berndt, Sonja I ; Giovannucci, E.L. ; Gronberg, H. ; Kote-Jarai, Zsofia ; Ma, Jun ; Muir, K. ; Stampfer, M. J. ; Stevens, V.L. ; Wiklund, Fredrik ; Willett, W.C. ; Goode, Ellen L. ; Permuth, J. B. ; Risch, Harvey A. ; Reid, B. M. ; Bezieau, S. ; Brenner, H. ; Chan, T.A. ; Chang-Claude, J. ; Hudson, T.J. ; Kocarnik, J. K. ; Newcomb, Polly A. ; Schoen, R.E. ; Slattery, M. L. ; White, E. ; Adank, M. A. ; Ahsan, H. ; Aittomaki, K. ; Baglietto, L. ; Blomquist, C. ; Canzian, F. ; Czene, K. ; dos Santos Silva, I. ; Eliassen, A. H. ; Figueroa, J.D. ; Flesch-Janys, D. ; Fletcher, O. ; Garcia-Closas, M. ; Gaudet, M. ; Johnson, N. ; Hall, P. ; Hazra, A. ; Hein, R. ; Hofman, A. ; Hopper, John L. ; Irwanto, A. ; Johansson, M. ; Kaaks, R. ; Kibriya, M.G. ; Lichtner, P. ; Liu, J. ; Lund, E. ; Makalic, E. ; Meindl, A. ; Muller-Myhsok, B. ; Muranen, Taru A. ; Nevanlinna, H. ; Peeters, Petra H. ; Peto, J. ; Prentice, R. L. ; Rahman, N. ; Sanchez, Anthony M. J. ; Schmidt, Daniel F. ; Schmutzler, Rita K. ; Southey, Melissa C. ; Tamimi, R. ; Travis, R.C. ; Turnbull, C. ; Uitterlinden, A. G. ; Wang, M. -Z. ; Whittemore, Alice S. ; Yang, X. H. R. ; Zheng, W. ; Buchanan, D. D. ; Casey, G. ; Conti, David V. ; Edlund, Christopher K. ; Gallinger, S. ; Haile, R. W. ; Jenkins, M. ; Le Marchand, L. ; Li, L. ; Lindor, N.M. ; Schmit, S. L. ; Thibodeau, S. N. ; Woods, M. O. ; Rafnar, T. ; Gudmundsson, J. ; Stacey, S.N. ; Stefansson, K. ; Sulem, P. ; Chen, A.Y. ; Tyrer, Jonathan P ; Christiani, David C. ; Wei, Y. ; Shen, H. B. ; Hu, Z. B. ; Shu, X.O. ; Shiraishi, K. ; Takahashi, A. ; Bosse, Y. ; Obeidat, M. ; Nickle, D. ; Timens, W. ; Freedman, Matthew L. ; Li, Y.Q. ; Seminara, D. ; Chanock, Stephen J ; Gong, J. ; Peters, U. ; Gruber, Stephen B. ; Amos, Christopher I. ; Sellers, Thomas A. ; Easton, Douglas F. ; Hunter, David J. ; Haiman, Christopher A. ; Henderson, B.E. ; Hung, Rayjean J. ; [Unknown], Ocac ; Consortium, Practical ; Hereditary Breast Ovarian Canc, Res ; Colorectal, Transdisciplinary ; African Amer Breast, Canc ; African Ancestry Prostate, Canc. / Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations : Cancer Research. In: Cancer Research. 2016 ; Vol. 76. pp. 5103-5114.
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title = "Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations: Cancer Research",
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 atCDKN2B-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. (C) 2016 AACR.",
author = "G. Fehringer and P. Kraft and Pharoah, {Paul D. P.} and Eeles, {Rosalind A.} and N. Chatterjee and Schumacher, {Fredrick R.} and Schildkraut, {Joellen M.} and S. Lindstrom and P. Brennan and H. Bickeboller and Houlston, {Richard S.} and M.T. Landi and N. Caporaso and A. Risch and {Al Olama}, {A. A.} and Berndt, {Sonja I} and E.L. Giovannucci and H. Gronberg and Zsofia Kote-Jarai and Jun Ma and K. Muir and Stampfer, {M. J.} and V.L. Stevens and Fredrik Wiklund and W.C. Willett and Goode, {Ellen L.} and Permuth, {J. B.} and Risch, {Harvey A.} and Reid, {B. M.} and S. Bezieau and H. Brenner and T.A. Chan and J. Chang-Claude and T.J. Hudson and Kocarnik, {J. K.} and Newcomb, {Polly A.} and R.E. Schoen and Slattery, {M. L.} and E. White and Adank, {M. A.} and H. Ahsan and K. Aittomaki and L. Baglietto and C. Blomquist and F. Canzian and K. Czene and {dos Santos Silva}, I. and Eliassen, {A. H.} and J.D. Figueroa and D. Flesch-Janys and O. Fletcher and M. Garcia-Closas and M. Gaudet and N. Johnson and P. Hall and A. Hazra and R. Hein and A. Hofman and Hopper, {John L.} and A. Irwanto and M. Johansson and R. Kaaks and M.G. Kibriya and P. Lichtner and J. Liu and E. Lund and E. Makalic and A. Meindl and B. Muller-Myhsok and Muranen, {Taru A.} and H. Nevanlinna and Peeters, {Petra H.} and J. Peto and Prentice, {R. L.} and N. Rahman and Sanchez, {Anthony M. J.} and Schmidt, {Daniel F.} and Schmutzler, {Rita K.} and Southey, {Melissa C.} and R. Tamimi and R.C. Travis and C. Turnbull and Uitterlinden, {A. G.} and Wang, {M. -Z.} and Whittemore, {Alice S.} and Yang, {X. H. R.} and W. Zheng and Buchanan, {D. D.} and G. Casey and Conti, {David V.} and Edlund, {Christopher K.} and S. Gallinger and Haile, {R. W.} and M. Jenkins and {Le Marchand}, L. and L. Li and N.M. Lindor and Schmit, {S. L.} and Thibodeau, {S. N.} and Woods, {M. O.} and T. Rafnar and J. Gudmundsson and S.N. Stacey and K. Stefansson and P. Sulem and A.Y. Chen and Tyrer, {Jonathan P} and Christiani, {David C.} and Y. Wei and Shen, {H. B.} and Hu, {Z. B.} and X.O. Shu and K. Shiraishi and A. Takahashi and Y. Bosse and M. Obeidat and D. Nickle and W. Timens and Freedman, {Matthew L.} and Y.Q. Li and D. Seminara and Chanock, {Stephen J} and J. Gong and U. Peters and Gruber, {Stephen B.} and Amos, {Christopher I.} and Sellers, {Thomas A.} and Easton, {Douglas F.} and Hunter, {David J.} and Haiman, {Christopher A.} and B.E. Henderson and Hung, {Rayjean J.} and Ocac [Unknown] and Practical Consortium and {Hereditary Breast Ovarian Canc}, Res and Transdisciplinary Colorectal and {African Amer Breast}, Canc and {African Ancestry Prostate}, Canc",
note = "M1 - 17 ISI Document Delivery No.: DU6BU Times Cited: 0 Cited Reference Count: 47 Fehringer, Gordon Kraft, Peter Pharoah, Paul D. Eeles, Rosalind A. Chatterjee, Nilanjan Schumacher, Fredrick R. Schildkraut, Joellen M. Lindstrom, Sara Brennan, Paul Bickeboller, Heike Houlston, Richard S. Landi, Maria Teresa Caporaso, Neil Risch, Angela Al Olama, Ali Amin Berndt, Sonja I. Giovannucci, Edward L. Gronberg, Henrik Kote-Jarai, Zsofia Ma, Jing Muir, Kenneth Stampfer, Meir J. Stevens, Victoria L. Wiklund, Fredrik Willett, Walter C. Goode, Ellen L. Permuth, Jennifer B. Risch, Harvey A. Reid, Brett M. Bezieau, Stephane Brenner, Hermann Chan, Andrew T. Chang-Claude, Jenny Hudson, Thomas J. Kocarnik, Jonathan K. Newcomb, Polly A. Schoen, Robert E. Slattery, Martha L. White, Emily Adank, Muriel A. Ahsan, Habibul Aittomaki, Kristiina Baglietto, Laura Blomquist, Carl Canzian, Federico Czene, Kamila dos-Santos-Silva, Isabel Eliassen, A. Heather Figueroa, Jonine D. Flesch-Janys, Dieter Fletcher, Olivia Garcia-Closas, Montserrat Gaudet, Mia M. Johnson, Nichola Hall, Per Hazra, Aditi Hein, Rebecca Hofman, Albert Hopper, John L. Irwanto, Astrid Johansson, Mattias Kaaks, Rudolf Kibriya, Muhammad G. Lichtner, Peter Liu, Jianjun Lund, Eiliv Makalic, Enes Meindl, Alfons Muller-Myhsok, Bertram Muranen, Taru A. Nevanlinna, Heli Peeters, Petra H. Peto, Julian Prentice, Ross L. Rahman, Nazneen Sanchez, Maria Jose Schmidt, Daniel F. Schmutzler, Rita K. Southey, Melissa C. Tamimi, Rulla Travis, Ruth C. Turnbull, Clare Uitterlinden, Andre 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 Le Marchand, Loic Li, Li Lindor, Noralene M. Schmit, Stephanie L. Thibodeau, Stephen N. Woods, Michael O. Rafnar, Thorunn Gudmundsson, Julius Stacey, Simon N. Stefansson, Kari Sulem, Patrick Chen, Y. Ann Tyrer, Jonathan P. Christiani, David C. Wei, Yongyue Shen, Hongbing Hu, Zhibin Shu, Xiao-Ou Shiraishi, Kouya Takahashi, Atsushi Bosse, Yohan Obeidat, Ma'en Nickle, David Timens, Wim Freedman, Matthew L. Li, Qiyuan Seminara, Daniela Chanock, Stephen J. Gong, Jian Peters, Ulrike Gruber, Stephen B. Amos, Christopher I. Sellers, Thomas A. Easton, Douglas F. Hunter, David J. Haiman, Christopher A. Henderson, Brian E. Hung, Rayjean J. Hung, Rayjean/A-7439-2013; Zheng, Wei/O-3351-2013; Brenner, Hermann/B-4627-2017; Risch, Angela/H-2669-2013 Zheng, Wei/0000-0003-1226-070X; Brenner, Hermann/0000-0002-6129-1572; Risch, Angela/0000-0002-8026-5505; Muranen, Taru/0000-0002-5895-1808; Houlston, Richard/0000-0002-5268-0242 Cancer Research UK [10119, 10124, A10118, A10119, A10124, A12014, A16561, A5660, A8339]; Medical Research Council [G0700491]; NCATS NIH HHS [UL1 TR001863]; NCI NIH HHS [R01 CA050385, P30 CA023108, P30 CA071789, R01 CA055769, R01 CA074386, R01 CA092824, R01 CA121197, R01 CA127219, R01 CA133996, U01 CA137088, U01 CA164973, U19 CA148065, U19 CA148107, U19 CA148112, U19 CA148127, U19 CA148537, UM1 CA167551, UM1 CA176726]; NIH HHS [S10 OD020069] 0 4 8 AMER ASSOC CANCER RESEARCH PHILADELPHIA CANCER RES",
year = "2016",
doi = "10.1158/0008-5472.can-15-2980",
language = "English",
volume = "76",
pages = "5103--5114",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",

}

Fehringer, G, Kraft, P, Pharoah, PDP, Eeles, RA, Chatterjee, N, Schumacher, FR, Schildkraut, JM, Lindstrom, S, Brennan, P, Bickeboller, H, Houlston, RS, Landi, MT, Caporaso, N, Risch, A, Al Olama, AA, Berndt, SI, Giovannucci, EL, Gronberg, H, Kote-Jarai, Z, Ma, J, Muir, K, Stampfer, MJ, Stevens, VL, Wiklund, F, Willett, WC, Goode, EL, Permuth, JB, Risch, HA, Reid, BM, Bezieau, S, Brenner, H, Chan, TA, Chang-Claude, J, Hudson, TJ, Kocarnik, JK, Newcomb, PA, Schoen, RE, Slattery, ML, White, E, Adank, MA, Ahsan, H, Aittomaki, K, Baglietto, L, Blomquist, C, Canzian, F, Czene, K, dos Santos Silva, I, Eliassen, AH, Figueroa, JD, Flesch-Janys, D, Fletcher, O, Garcia-Closas, M, Gaudet, M, Johnson, N, Hall, P, Hazra, A, Hein, R, Hofman, A, Hopper, JL, Irwanto, A, Johansson, M, Kaaks, R, Kibriya, MG, Lichtner, P, Liu, J, Lund, E, Makalic, E, Meindl, A, Muller-Myhsok, B, Muranen, TA, Nevanlinna, H, Peeters, PH, Peto, J, Prentice, RL, Rahman, N, Sanchez, AMJ, Schmidt, DF, Schmutzler, RK, Southey, MC, Tamimi, R, Travis, RC, Turnbull, C, Uitterlinden, AG, Wang, M-Z, Whittemore, AS, Yang, XHR, Zheng, W, Buchanan, DD, Casey, G, Conti, DV, Edlund, CK, Gallinger, S, Haile, RW, Jenkins, M, Le Marchand, L, Li, L, Lindor, NM, Schmit, SL, Thibodeau, SN, Woods, MO, Rafnar, T, Gudmundsson, J, Stacey, SN, Stefansson, K, Sulem, P, Chen, AY, Tyrer, JP, Christiani, DC, Wei, Y, Shen, HB, Hu, ZB, Shu, XO, Shiraishi, K, Takahashi, A, Bosse, Y, Obeidat, M, Nickle, D, Timens, W, Freedman, ML, Li, YQ, Seminara, D, Chanock, SJ, Gong, J, Peters, U, Gruber, SB, Amos, CI, Sellers, TA, Easton, DF, Hunter, DJ, Haiman, CA, Henderson, BE, Hung, RJ, [Unknown], O, Consortium, P, Hereditary Breast Ovarian Canc, R, Colorectal, T, African Amer Breast, C & African Ancestry Prostate, C 2016, 'Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations: Cancer Research' Cancer Research, vol. 76, pp. 5103-5114. https://doi.org/10.1158/0008-5472.can-15-2980

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations : Cancer Research. / Fehringer, G.; Kraft, P.; Pharoah, Paul D. P.; Eeles, Rosalind A.; Chatterjee, N.; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindstrom, S.; Brennan, P.; Bickeboller, H.; Houlston, Richard S.; Landi, M.T.; Caporaso, N.; Risch, A.; Al Olama, A. A.; Berndt, Sonja I; Giovannucci, E.L.; Gronberg, H.; Kote-Jarai, Zsofia; Ma, Jun; Muir, K.; Stampfer, M. J.; Stevens, V.L.; Wiklund, Fredrik; Willett, W.C.; Goode, Ellen L.; Permuth, J. B.; Risch, Harvey A.; Reid, B. M.; Bezieau, S.; Brenner, H.; Chan, T.A.; Chang-Claude, J.; Hudson, T.J.; Kocarnik, J. K.; Newcomb, Polly A.; Schoen, R.E.; Slattery, M. L.; White, E.; Adank, M. A.; Ahsan, H.; Aittomaki, K.; Baglietto, L.; Blomquist, C.; Canzian, F.; Czene, K.; dos Santos Silva, I.; Eliassen, A. H.; Figueroa, J.D.; Flesch-Janys, D.; Fletcher, O.; Garcia-Closas, M.; Gaudet, M.; Johnson, N.; Hall, P.; Hazra, A.; Hein, R.; Hofman, A.; Hopper, John L.; Irwanto, A.; Johansson, M.; Kaaks, R.; Kibriya, M.G.; Lichtner, P.; Liu, J.; Lund, E.; Makalic, E.; Meindl, A.; Muller-Myhsok, B.; Muranen, Taru A.; Nevanlinna, H.; Peeters, Petra H.; Peto, J.; Prentice, R. L.; Rahman, N.; Sanchez, Anthony M. J.; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, R.; Travis, R.C.; Turnbull, C.; Uitterlinden, A. G.; Wang, M. -Z.; Whittemore, Alice S.; Yang, X. H. R.; Zheng, W.; Buchanan, D. D.; Casey, G.; Conti, David V.; Edlund, Christopher K.; Gallinger, S.; Haile, R. W.; Jenkins, M.; Le Marchand, L.; Li, L.; Lindor, N.M.; Schmit, S. L.; Thibodeau, S. N.; Woods, M. O.; Rafnar, T.; Gudmundsson, J.; Stacey, S.N.; Stefansson, K.; Sulem, P.; Chen, A.Y.; Tyrer, Jonathan P; Christiani, David C.; Wei, Y.; Shen, H. B.; Hu, Z. B.; Shu, X.O.; Shiraishi, K.; Takahashi, A.; Bosse, Y.; Obeidat, M.; Nickle, D.; Timens, W.; Freedman, Matthew L.; Li, Y.Q.; Seminara, D.; Chanock, Stephen J; Gong, J.; Peters, U.; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, B.E.; Hung, Rayjean J.; [Unknown], Ocac; Consortium, Practical; Hereditary Breast Ovarian Canc, Res; Colorectal, Transdisciplinary; African Amer Breast, Canc; African Ancestry Prostate, Canc.

In: Cancer Research, Vol. 76, 2016, p. 5103-5114.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

T2 - Cancer Research

AU - Fehringer, G.

AU - Kraft, P.

AU - Pharoah, Paul D. P.

AU - Eeles, Rosalind A.

AU - Chatterjee, N.

AU - Schumacher, Fredrick R.

AU - Schildkraut, Joellen M.

AU - Lindstrom, S.

AU - Brennan, P.

AU - Bickeboller, H.

AU - Houlston, Richard S.

AU - Landi, M.T.

AU - Caporaso, N.

AU - Risch, A.

AU - Al Olama, A. A.

AU - Berndt, Sonja I

AU - Giovannucci, E.L.

AU - Gronberg, H.

AU - Kote-Jarai, Zsofia

AU - Ma, Jun

AU - Muir, K.

AU - Stampfer, M. J.

AU - Stevens, V.L.

AU - Wiklund, Fredrik

AU - Willett, W.C.

AU - Goode, Ellen L.

AU - Permuth, J. B.

AU - Risch, Harvey A.

AU - Reid, B. M.

AU - Bezieau, S.

AU - Brenner, H.

AU - Chan, T.A.

AU - Chang-Claude, J.

AU - Hudson, T.J.

AU - Kocarnik, J. K.

AU - Newcomb, Polly A.

AU - Schoen, R.E.

AU - Slattery, M. L.

AU - White, E.

AU - Adank, M. A.

AU - Ahsan, H.

AU - Aittomaki, K.

AU - Baglietto, L.

AU - Blomquist, C.

AU - Canzian, F.

AU - Czene, K.

AU - dos Santos Silva, I.

AU - Eliassen, A. H.

AU - Figueroa, J.D.

AU - Flesch-Janys, D.

AU - Fletcher, O.

AU - Garcia-Closas, M.

AU - Gaudet, M.

AU - Johnson, N.

AU - Hall, P.

AU - Hazra, A.

AU - Hein, R.

AU - Hofman, A.

AU - Hopper, John L.

AU - Irwanto, A.

AU - Johansson, M.

AU - Kaaks, R.

AU - Kibriya, M.G.

AU - Lichtner, P.

AU - Liu, J.

AU - Lund, E.

AU - Makalic, E.

AU - Meindl, A.

AU - Muller-Myhsok, B.

AU - Muranen, Taru A.

AU - Nevanlinna, H.

AU - Peeters, Petra H.

AU - Peto, J.

AU - Prentice, R. L.

AU - Rahman, N.

AU - Sanchez, Anthony M. J.

AU - Schmidt, Daniel F.

AU - Schmutzler, Rita K.

AU - Southey, Melissa C.

AU - Tamimi, R.

AU - Travis, R.C.

AU - Turnbull, C.

AU - Uitterlinden, A. G.

AU - Wang, M. -Z.

AU - Whittemore, Alice S.

AU - Yang, X. H. R.

AU - Zheng, W.

AU - Buchanan, D. D.

AU - Casey, G.

AU - Conti, David V.

AU - Edlund, Christopher K.

AU - Gallinger, S.

AU - Haile, R. W.

AU - Jenkins, M.

AU - Le Marchand, L.

AU - Li, L.

AU - Lindor, N.M.

AU - Schmit, S. L.

AU - Thibodeau, S. N.

AU - Woods, M. O.

AU - Rafnar, T.

AU - Gudmundsson, J.

AU - Stacey, S.N.

AU - Stefansson, K.

AU - Sulem, P.

AU - Chen, A.Y.

AU - Tyrer, Jonathan P

AU - Christiani, David C.

AU - Wei, Y.

AU - Shen, H. B.

AU - Hu, Z. B.

AU - Shu, X.O.

AU - Shiraishi, K.

AU - Takahashi, A.

AU - Bosse, Y.

AU - Obeidat, M.

AU - Nickle, D.

AU - Timens, W.

AU - Freedman, Matthew L.

AU - Li, Y.Q.

AU - Seminara, D.

AU - Chanock, Stephen J

AU - Gong, J.

AU - Peters, U.

AU - Gruber, Stephen B.

AU - Amos, Christopher I.

AU - Sellers, Thomas A.

AU - Easton, Douglas F.

AU - Hunter, David J.

AU - Haiman, Christopher A.

AU - Henderson, B.E.

AU - Hung, Rayjean J.

AU - [Unknown], Ocac

AU - Consortium, Practical

AU - Hereditary Breast Ovarian Canc, Res

AU - Colorectal, Transdisciplinary

AU - African Amer Breast, Canc

AU - African Ancestry Prostate, Canc

N1 - M1 - 17 ISI Document Delivery No.: DU6BU Times Cited: 0 Cited Reference Count: 47 Fehringer, Gordon Kraft, Peter Pharoah, Paul D. Eeles, Rosalind A. Chatterjee, Nilanjan Schumacher, Fredrick R. Schildkraut, Joellen M. Lindstrom, Sara Brennan, Paul Bickeboller, Heike Houlston, Richard S. Landi, Maria Teresa Caporaso, Neil Risch, Angela Al Olama, Ali Amin Berndt, Sonja I. Giovannucci, Edward L. Gronberg, Henrik Kote-Jarai, Zsofia Ma, Jing Muir, Kenneth Stampfer, Meir J. Stevens, Victoria L. Wiklund, Fredrik Willett, Walter C. Goode, Ellen L. Permuth, Jennifer B. Risch, Harvey A. Reid, Brett M. Bezieau, Stephane Brenner, Hermann Chan, Andrew T. Chang-Claude, Jenny Hudson, Thomas J. Kocarnik, Jonathan K. Newcomb, Polly A. Schoen, Robert E. Slattery, Martha L. White, Emily Adank, Muriel A. Ahsan, Habibul Aittomaki, Kristiina Baglietto, Laura Blomquist, Carl Canzian, Federico Czene, Kamila dos-Santos-Silva, Isabel Eliassen, A. Heather Figueroa, Jonine D. Flesch-Janys, Dieter Fletcher, Olivia Garcia-Closas, Montserrat Gaudet, Mia M. Johnson, Nichola Hall, Per Hazra, Aditi Hein, Rebecca Hofman, Albert Hopper, John L. Irwanto, Astrid Johansson, Mattias Kaaks, Rudolf Kibriya, Muhammad G. Lichtner, Peter Liu, Jianjun Lund, Eiliv Makalic, Enes Meindl, Alfons Muller-Myhsok, Bertram Muranen, Taru A. Nevanlinna, Heli Peeters, Petra H. Peto, Julian Prentice, Ross L. Rahman, Nazneen Sanchez, Maria Jose Schmidt, Daniel F. Schmutzler, Rita K. Southey, Melissa C. Tamimi, Rulla Travis, Ruth C. Turnbull, Clare Uitterlinden, Andre 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 Le Marchand, Loic Li, Li Lindor, Noralene M. Schmit, Stephanie L. Thibodeau, Stephen N. Woods, Michael O. Rafnar, Thorunn Gudmundsson, Julius Stacey, Simon N. Stefansson, Kari Sulem, Patrick Chen, Y. Ann Tyrer, Jonathan P. Christiani, David C. Wei, Yongyue Shen, Hongbing Hu, Zhibin Shu, Xiao-Ou Shiraishi, Kouya Takahashi, Atsushi Bosse, Yohan Obeidat, Ma'en Nickle, David Timens, Wim Freedman, Matthew L. Li, Qiyuan Seminara, Daniela Chanock, Stephen J. Gong, Jian Peters, Ulrike Gruber, Stephen B. Amos, Christopher I. Sellers, Thomas A. Easton, Douglas F. Hunter, David J. Haiman, Christopher A. Henderson, Brian E. Hung, Rayjean J. Hung, Rayjean/A-7439-2013; Zheng, Wei/O-3351-2013; Brenner, Hermann/B-4627-2017; Risch, Angela/H-2669-2013 Zheng, Wei/0000-0003-1226-070X; Brenner, Hermann/0000-0002-6129-1572; Risch, Angela/0000-0002-8026-5505; Muranen, Taru/0000-0002-5895-1808; Houlston, Richard/0000-0002-5268-0242 Cancer Research UK [10119, 10124, A10118, A10119, A10124, A12014, A16561, A5660, A8339]; Medical Research Council [G0700491]; NCATS NIH HHS [UL1 TR001863]; NCI NIH HHS [R01 CA050385, P30 CA023108, P30 CA071789, R01 CA055769, R01 CA074386, R01 CA092824, R01 CA121197, R01 CA127219, R01 CA133996, U01 CA137088, U01 CA164973, U19 CA148065, U19 CA148107, U19 CA148112, U19 CA148127, U19 CA148537, UM1 CA167551, UM1 CA176726]; NIH HHS [S10 OD020069] 0 4 8 AMER ASSOC CANCER RESEARCH PHILADELPHIA CANCER RES

PY - 2016

Y1 - 2016

N2 - 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 atCDKN2B-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. (C) 2016 AACR.

AB - 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 atCDKN2B-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. (C) 2016 AACR.

U2 - 10.1158/0008-5472.can-15-2980

DO - 10.1158/0008-5472.can-15-2980

M3 - Article

VL - 76

SP - 5103

EP - 5114

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

ER -