Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

Gordon Fehringer; Peter Kraft; Paul D. Pharoah; Rosalind A. Eeles; Nilanjan Chatterjee; Fredrick R. Schumacher; Joellen M. Schildkraut; Sara Lindström; Paul Brennan; Heike Bickeböller; Richard S. Houlston; Maria Teresa Landi; Neil Caporaso; Angela Risch; Ali Amin Al Olama; Sonja I. Berndt; Edward L. Giovannucci; Henrik Grönberg; Zsofia Kote-Jarai; Jing Ma; Kenneth Muir; Meir J. Stampfer; Victoria L. Stevens; Fredrik Wiklund; Walter C. Willett; Ellen L. Goode; Jennifer B. Permuth; Harvey A. Risch; Brett M. Reid; Stephane Bezieau; Hermann Brenner; Andrew T. Chan; Jenny Chang-Claude; Thomas J. Hudson; Jonathan K. Kocarnik; Polly A. Newcomb; Robert E. Schoen; Martha L. Slattery; Emily White; Muriel A. Adank; Habibul Ahsan; Kristiina Aittomäki; Laura Baglietto; Carl Blomquist; Federico Canzian; Kamila Czene; Isabel Dos-Santos-silva; A. Heather Eliassen; Jonine D. Figueroa; Dieter Flesch-Janys; Olivia Fletcher; Montserrat Garcia-Closas; Mia M. Gaudet; Nichola Johnson; Per Hall; Aditi Hazra; Rebecca Hein; Albert Hofman; John L. Hopper; Astrid Irwanto; Mattias Johansson; Rudolf Kaaks; Muhammad G. Kibriya; Peter Lichtner; Jianjun Liu; Eiliv Lund; Enes Makalic; Alfons Meindl; Bertram Müller-Myhsok; Taru A. Muranen; Heli Nevanlinna; Petra H. Peeters; Julian Peto; Ross L. Prentice; Nazneen Rahman; Maria Jose Sanchez; Daniel F. Schmidt; Rita K. Schmutzler; Melissa C. Southey; Rulla Tamimi; Ruth C. Travis; Clare Turnbull; Andre G. Uitterlinden; Zhaoming Wang; Alice S. Whittemore; Xiaohong R. Yang; Wei Zheng; Daniel D. Buchanan; Graham Casey; David V. Conti; Christopher K. Edlund; Steven Gallinger; Robert W. Haile; Mark Jenkins; Loïcle Marchand; Li Li; Noralene M. Lindor; Stephanie L. Schmit; Stephen N. Thibodeau; Michael O. Woods; Thorunn Rafnar; Julius Gudmundsson; Simon N. Stacey; Kari Stefansson; Patrick Sulem; Y. Ann Chen; Jonathan P. Tyrer; David C. Christiani; Yongyue Wei; Hongbing Shen; Zhibin Hu; Xiao Ou Shu; Kouya Shiraishi; Atsushi Takahashi; Yohan Bossé; Ma'en Obeidat; David Nickle; Wim Timens; Matthew L. Freedman; Qiyuan Li; Daniela Seminara; Stephen J. Chanock; Jian Gong; Ulrike Peters; Stephen B. Gruber; Christopher I. Amos; Thomas A. Sellers; Douglas F. Easton; David J. Hunter; Christopher A. Haiman; Brian E. Henderson; Rayjean J. Hung

doi:10.1158/0008-5472.CAN-15-2980

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

Gordon Fehringer, Peter Kraft, Paul D. Pharoah, Rosalind A. Eeles, Nilanjan Chatterjee, Fredrick R. Schumacher, Joellen M. Schildkraut, Sara Lindström, Paul Brennan, Heike Bickeböller, Richard S. Houlston, Maria Teresa Landi, Neil Caporaso, Angela Risch, Ali Amin Al Olama, Sonja I. Berndt, Edward L. Giovannucci, Henrik Grönberg, Zsofia Kote-Jarai, Jing MaKenneth Muir, Meir J. Stampfer, Victoria L. Stevens, Fredrik Wiklund, Walter C. Willett, Ellen L. Goode, Jennifer B. Permuth, Harvey A. Risch, Brett M. Reid, Stephane Bezieau, Hermann Brenner, Andrew T. Chan, Jenny Chang-Claude, Thomas J. Hudson, Jonathan K. Kocarnik, Polly A. Newcomb, Robert E. Schoen, Martha L. Slattery, Emily White, Muriel A. Adank, Habibul Ahsan, Kristiina Aittomäki, Laura Baglietto, Carl Blomquist, Federico Canzian, Kamila Czene, Isabel Dos-Santos-silva, A. Heather Eliassen, Jonine D. Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Montserrat Garcia-Closas, Mia M. Gaudet, Nichola Johnson, Per Hall, Aditi Hazra, Rebecca Hein, Albert Hofman, John L. Hopper, Astrid Irwanto, Mattias Johansson, Rudolf Kaaks, Muhammad G. Kibriya, Peter Lichtner, Jianjun Liu, Eiliv Lund, Enes Makalic, Alfons Meindl, Bertram Müller-Myhsok, Taru A. Muranen, Heli Nevanlinna, Petra H. Peeters, Julian Peto, Ross L. Prentice, Nazneen Rahman, Maria Jose Sanchez, Daniel F. Schmidt, Rita K. Schmutzler, Melissa C. Southey, Rulla Tamimi, Ruth C. Travis, Clare Turnbull, Andre G. Uitterlinden, Zhaoming Wang, Alice S. Whittemore, Xiaohong R. Yang, Wei Zheng, Daniel D. Buchanan, Graham Casey, David V. Conti, Christopher K. Edlund, Steven Gallinger, Robert W. Haile, Mark Jenkins, Loïcle Marchand, Li Li, Noralene M. Lindor, Stephanie L. Schmit, Stephen N. Thibodeau, Michael O. Woods, Thorunn Rafnar, Julius Gudmundsson, Simon N. Stacey, Kari Stefansson, Patrick Sulem, Y. Ann Chen, Jonathan P. Tyrer, David C. Christiani, Yongyue Wei, Hongbing Shen, Zhibin Hu, Xiao Ou Shu, Kouya Shiraishi, Atsushi Takahashi, Yohan Bossé, Ma'en Obeidat, David Nickle, Wim Timens, Matthew L. Freedman, Qiyuan Li, Daniela Seminara, Stephen J. Chanock, Jian Gong, Ulrike Peters, Stephen B. Gruber, Christopher I. Amos, Thomas A. Sellers, Douglas F. Easton, David J. Hunter, Christopher A. Haiman, Brian E. Henderson, Rayjean J. Hung^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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 at CDKN2BAS1 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 cancerassociated loci, identifying common mechanisms of cancer development and progression.

Original language	English
Pages (from-to)	5103-5114
Number of pages	12
Journal	Cancer Research
Volume	76
Issue number	17
DOIs	https://doi.org/10.1158/0008-5472.CAN-15-2980
Publication status	Published - 1 Sept 2016

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10.1158/0008-5472.CAN-15-2980

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Fehringer, G., Kraft, P., Pharoah, P. D., Eeles, R. A., Chatterjee, N., Schumacher, F. R., Schildkraut, J. M., Lindström, S., Brennan, P., Bickeböller, H., Houlston, R. S., Landi, M. T., Caporaso, N., Risch, A., Al Olama, A. A., Berndt, S. I., Giovannucci, E. L., Grönberg, H., Kote-Jarai, Z., ... Hung, R. J. (2016). Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations. Cancer Research, 76(17), 5103-5114. https://doi.org/10.1158/0008-5472.CAN-15-2980

@article{39a2e08226a44225b7a8912086e09dec,

title = "Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations",

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 CDKN2BAS1 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 cancerassociated loci, identifying common mechanisms of cancer development and progression.",

author = "Gordon Fehringer and Peter Kraft and Pharoah, \{Paul D.\} and Eeles, \{Rosalind A.\} and Nilanjan Chatterjee and Schumacher, \{Fredrick R.\} and Schildkraut, \{Joellen M.\} and Sara Lindstr{\"o}m and Paul Brennan and Heike Bickeb{\"o}ller and Houlston, \{Richard S.\} and Landi, \{Maria Teresa\} and Neil Caporaso and Angela Risch and \{Al Olama\}, \{Ali Amin\} and Berndt, \{Sonja I.\} and Giovannucci, \{Edward L.\} and Henrik Gr{\"o}nberg and Zsofia Kote-Jarai and Jing Ma and Kenneth Muir and Stampfer, \{Meir J.\} and Stevens, \{Victoria L.\} and Fredrik Wiklund and Willett, \{Walter C.\} and Goode, \{Ellen L.\} and Permuth, \{Jennifer B.\} and Risch, \{Harvey A.\} and Reid, \{Brett M.\} and Stephane Bezieau and Hermann Brenner and Chan, \{Andrew T.\} and Jenny Chang-Claude and Hudson, \{Thomas J.\} and Kocarnik, \{Jonathan K.\} and Newcomb, \{Polly A.\} and Schoen, \{Robert E.\} and Slattery, \{Martha L.\} and Emily White and Adank, \{Muriel A.\} and Habibul Ahsan and Kristiina Aittom{\"a}ki and Laura Baglietto and Carl Blomquist and Federico Canzian and Kamila Czene and Isabel Dos-Santos-silva and Eliassen, \{A. Heather\} and Figueroa, \{Jonine D.\} and Dieter Flesch-Janys and Olivia Fletcher and Montserrat Garcia-Closas and Gaudet, \{Mia M.\} and Nichola Johnson and Per Hall and Aditi Hazra and Rebecca Hein and Albert Hofman and Hopper, \{John L.\} and Astrid Irwanto and Mattias Johansson and Rudolf Kaaks and Kibriya, \{Muhammad G.\} and Peter Lichtner and Jianjun Liu and Eiliv Lund and Enes Makalic and Alfons Meindl and Bertram M{\"u}ller-Myhsok and Muranen, \{Taru A.\} and Heli Nevanlinna and Peeters, \{Petra H.\} and Julian Peto and Prentice, \{Ross L.\} and Nazneen Rahman and Sanchez, \{Maria Jose\} and Schmidt, \{Daniel F.\} and Schmutzler, \{Rita K.\} and Southey, \{Melissa C.\} and Rulla Tamimi and Travis, \{Ruth C.\} and Clare Turnbull and Uitterlinden, \{Andre G.\} and Zhaoming Wang and Whittemore, \{Alice S.\} and Yang, \{Xiaohong R.\} and Wei Zheng and Buchanan, \{Daniel D.\} and Graham Casey and Conti, \{David V.\} and Edlund, \{Christopher K.\} and Steven Gallinger and Haile, \{Robert W.\} and Mark Jenkins and Lo{\"i}cle Marchand and Li Li and Lindor, \{Noralene M.\} and Schmit, \{Stephanie L.\} and Thibodeau, \{Stephen N.\} and Woods, \{Michael O.\} and Thorunn Rafnar and Julius Gudmundsson and Stacey, \{Simon N.\} and Kari Stefansson and Patrick Sulem and Chen, \{Y. Ann\} and Tyrer, \{Jonathan P.\} and Christiani, \{David C.\} and Yongyue Wei and Hongbing Shen and Zhibin Hu and Shu, \{Xiao Ou\} and Kouya Shiraishi and Atsushi Takahashi and Yohan Boss{\'e} and Ma'en Obeidat and David Nickle and Wim Timens and Freedman, \{Matthew L.\} and Qiyuan Li and Daniela Seminara and Chanock, \{Stephen J.\} and Jian Gong and Ulrike 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 Henderson, \{Brian E.\} and Hung, \{Rayjean J.\}",

year = "2016",

month = sep,

day = "1",

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.",

number = "17",

}

Fehringer, G, Kraft, P, Pharoah, PD, Eeles, RA, Chatterjee, N, Schumacher, FR, Schildkraut, JM, Lindström, S, Brennan, P, Bickeböller, H, Houlston, RS, Landi, MT, Caporaso, N, Risch, A, Al Olama, AA, Berndt, SI, Giovannucci, EL, Grönberg, 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, AT, Chang-Claude, J, Hudson, TJ, Kocarnik, JK, Newcomb, PA, Schoen, RE, Slattery, ML, White, E, Adank, MA, Ahsan, H, Aittomäki, 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, MM, 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, Müller-Myhsok, B, Muranen, TA, Nevanlinna, H, Peeters, PH, Peto, J, Prentice, RL, Rahman, N, Sanchez, MJ, Schmidt, DF, Schmutzler, RK, Southey, MC, Tamimi, R, Travis, RC, Turnbull, C, Uitterlinden, AG, Wang, Z, Whittemore, AS, Yang, XR, Zheng, W, Buchanan, DD, Casey, G, Conti, DV, Edlund, CK, Gallinger, S, Haile, RW, Jenkins, M, Marchand, L, Li, L, Lindor, NM, Schmit, SL, Thibodeau, SN, Woods, MO, Rafnar, T, Gudmundsson, J, Stacey, SN, Stefansson, K, Sulem, P, Chen, YA, Tyrer, JP, Christiani, DC, Wei, Y, Shen, H, Hu, Z, Shu, XO, Shiraishi, K, Takahashi, A, Bossé, Y, Obeidat, M, Nickle, D, Timens, W, Freedman, ML, Li, Q, Seminara, D, Chanock, SJ, Gong, J, Peters, U, Gruber, SB, Amos, CI, Sellers, TA, Easton, DF, Hunter, DJ, Haiman, CA, Henderson, BE & Hung, RJ 2016, 'Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations', Cancer Research, vol. 76, no. 17, pp. 5103-5114. https://doi.org/10.1158/0008-5472.CAN-15-2980

TY - JOUR

T1 - Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

AU - Fehringer, Gordon

AU - Kraft, Peter

AU - Pharoah, Paul D.

AU - Eeles, Rosalind A.

AU - Chatterjee, Nilanjan

AU - Schumacher, Fredrick R.

AU - Schildkraut, Joellen M.

AU - Lindström, Sara

AU - Brennan, Paul

AU - Bickeböller, Heike

AU - Houlston, Richard S.

AU - Landi, Maria Teresa

AU - Caporaso, Neil

AU - Risch, Angela

AU - Al Olama, Ali Amin

AU - Berndt, Sonja I.

AU - Giovannucci, Edward L.

AU - Grönberg, Henrik

AU - Kote-Jarai, Zsofia

AU - Ma, Jing

AU - Muir, Kenneth

AU - Stampfer, Meir J.

AU - Stevens, Victoria L.

AU - Wiklund, Fredrik

AU - Willett, Walter C.

AU - Goode, Ellen L.

AU - Permuth, Jennifer B.

AU - Risch, Harvey A.

AU - Reid, Brett M.

AU - Bezieau, Stephane

AU - Brenner, Hermann

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Hudson, Thomas J.

AU - Kocarnik, Jonathan K.

AU - Newcomb, Polly A.

AU - Schoen, Robert E.

AU - Slattery, Martha L.

AU - White, Emily

AU - Adank, Muriel A.

AU - Ahsan, Habibul

AU - Aittomäki, Kristiina

AU - Baglietto, Laura

AU - Blomquist, Carl

AU - Canzian, Federico

AU - Czene, Kamila

AU - Dos-Santos-silva, Isabel

AU - Eliassen, A. Heather

AU - Figueroa, Jonine D.

AU - Flesch-Janys, Dieter

AU - Fletcher, Olivia

AU - Garcia-Closas, Montserrat

AU - Gaudet, Mia M.

AU - Johnson, Nichola

AU - Hall, Per

AU - Hazra, Aditi

AU - Hein, Rebecca

AU - Hofman, Albert

AU - Hopper, John L.

AU - Irwanto, Astrid

AU - Johansson, Mattias

AU - Kaaks, Rudolf

AU - Kibriya, Muhammad G.

AU - Lichtner, Peter

AU - Liu, Jianjun

AU - Lund, Eiliv

AU - Makalic, Enes

AU - Meindl, Alfons

AU - Müller-Myhsok, Bertram

AU - Muranen, Taru A.

AU - Nevanlinna, Heli

AU - Peeters, Petra H.

AU - Peto, Julian

AU - Prentice, Ross L.

AU - Rahman, Nazneen

AU - Sanchez, Maria Jose

AU - Schmidt, Daniel F.

AU - Schmutzler, Rita K.

AU - Southey, Melissa C.

AU - Tamimi, Rulla

AU - Travis, Ruth C.

AU - Turnbull, Clare

AU - Uitterlinden, Andre G.

AU - Wang, Zhaoming

AU - Whittemore, Alice S.

AU - Yang, Xiaohong R.

AU - Zheng, Wei

AU - Buchanan, Daniel D.

AU - Casey, Graham

AU - Conti, David V.

AU - Edlund, Christopher K.

AU - Gallinger, Steven

AU - Haile, Robert W.

AU - Jenkins, Mark

AU - Marchand, Loïcle

AU - Li, Li

AU - Lindor, Noralene M.

AU - Schmit, Stephanie L.

AU - Thibodeau, Stephen N.

AU - Woods, Michael O.

AU - Rafnar, Thorunn

AU - Gudmundsson, Julius

AU - Stacey, Simon N.

AU - Stefansson, Kari

AU - Sulem, Patrick

AU - Chen, Y. Ann

AU - Tyrer, Jonathan P.

AU - Christiani, David C.

AU - Wei, Yongyue

AU - Shen, Hongbing

AU - Hu, Zhibin

AU - Shu, Xiao Ou

AU - Shiraishi, Kouya

AU - Takahashi, Atsushi

AU - Bossé, Yohan

AU - Obeidat, Ma'en

AU - Nickle, David

AU - Timens, Wim

AU - Freedman, Matthew L.

AU - Li, Qiyuan

AU - Seminara, Daniela

AU - Chanock, Stephen J.

AU - Gong, Jian

AU - Peters, Ulrike

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, Brian E.

AU - Hung, Rayjean J.

PY - 2016/9/1

Y1 - 2016/9/1

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 at CDKN2BAS1 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 cancerassociated loci, identifying common mechanisms of cancer development and progression.

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 at CDKN2BAS1 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 cancerassociated loci, identifying common mechanisms of cancer development and progression.

UR - https://www.scopus.com/pages/publications/84986888945

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

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

M3 - Article

C2 - 27197191

AN - SCOPUS:84986888945

SN - 0008-5472

VL - 76

SP - 5103

EP - 5114

JO - Cancer Research

JF - Cancer Research

IS - 17

ER -

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

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