Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Fredrick R. Schumacher; Stephanie L. Schmit; Shuo Jiao; Christopher K. Edlund; Hansong Wang; Ben Zhang; Li Hsu; Shu Chen Huang; Christopher P. Fischer; John F. Harju; Gregory E. Idos; Flavio Lejbkowicz; Frank J. Manion; Kevin McDonnell; Caroline E. McNeil; Marilena Melas; Hedy S. Rennert; Wei Shi; Duncan C. Thomas; David J. Van Den Berg; Carolyn M. Hutter; Aaron K. Aragaki; Katja Butterbach; Bette J. Caan; Christopher S. Carlson; Stephen J. Chanock; Keith R. Curtis; Charles S. Fuchs; Manish Gala; Edward L. Giocannucci; Stephanie M. Gogarten; Richard B. Hayes; Brian Henderson; David J. Hunter; Rebecca D. Jackson; Laurence N. Kolonel; Charles Kooperberg; Sebastian Kury; Andrea Lacroix; Cathy C. Laurie; Cecelia A. Laurie; Mathiew Lemire; David Levine; Jing Ma; Karen W. Makar; Conghui Qu; Darin Taverna; Cornelia M. Ulrich; Kana Wu; Suminori Kono; Dee W. West; Sonja I. Berndt; Stephane Bezieau; Hermann Brenner; Peter T. Campbell; Andrew T. Chan; Jenny Chang-Claude; Gerhard A. Coetzee; David V. Conti; David Duggan; Jane C. Figueiredo; Barbara K. Fortini; Steven J. Gallinger; W. James Gauderman; Graham Giles; Roger Green; Robert Haile; Tabitha A. Harrison; Michael Hoffmeister; John L. Hopper; Thomas J. Hudson; Eric Jacobs; Motoki Iwasaki; Sun Ha Jee; Mark Jenkins; Wei Hua Jia; Amit Joshi; Li Li; Noralene M. Lindor; Keitaro Matsuo; Victor Moreno; Bhramar Mukherjee; Polly A. Newcomb; John D. Potter; Leon Raskin; Gad Rennert; Stephanie Rosse; Gianluca Severi; Robert E. Schoen; Daniela Seminara; Xiao Ou Shu; Martha L. Slattery; Shoichiro Tsugane; Emily White; Yong Bing Xiang; Brent W. Zanke; Wei Zheng; Loic Le Marchand; Graham Casey; Stephen B. Gruber; Ulrike Peters

doi:10.1038/ncomms8138

Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Fredrick R. Schumacher, Stephanie L. Schmit, Shuo Jiao, Christopher K. Edlund, Hansong Wang, Ben Zhang, Li Hsu, Shu Chen Huang, Christopher P. Fischer, John F. Harju, Gregory E. Idos, Flavio Lejbkowicz, Frank J. Manion, Kevin McDonnell, Caroline E. McNeil, Marilena Melas, Hedy S. Rennert, Wei Shi, Duncan C. Thomas, David J. Van Den BergCarolyn M. Hutter, Aaron K. Aragaki, Katja Butterbach, Bette J. Caan, Christopher S. Carlson, Stephen J. Chanock, Keith R. Curtis, Charles S. Fuchs, Manish Gala, Edward L. Giocannucci, Stephanie M. Gogarten, Richard B. Hayes, Brian Henderson, David J. Hunter, Rebecca D. Jackson, Laurence N. Kolonel, Charles Kooperberg, Sebastian Kury, Andrea Lacroix, Cathy C. Laurie, Cecelia A. Laurie, Mathiew Lemire, David Levine, Jing Ma, Karen W. Makar, Conghui Qu, Darin Taverna, Cornelia M. Ulrich, Kana Wu, Suminori Kono, Dee W. West, Sonja I. Berndt, Stephane Bezieau, Hermann Brenner, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Gerhard A. Coetzee, David V. Conti, David Duggan, Jane C. Figueiredo, Barbara K. Fortini, Steven J. Gallinger, W. James Gauderman, Graham Giles, Roger Green, Robert Haile, Tabitha A. Harrison, Michael Hoffmeister, John L. Hopper, Thomas J. Hudson, Eric Jacobs, Motoki Iwasaki, Sun Ha Jee, Mark Jenkins, Wei Hua Jia, Amit Joshi, Li Li, Noralene M. Lindor, Keitaro Matsuo, Victor Moreno, Bhramar Mukherjee, Polly A. Newcomb, John D. Potter, Leon Raskin, Gad Rennert, Stephanie Rosse, Gianluca Severi, Robert E. Schoen, Daniela Seminara, Xiao Ou Shu, Martha L. Slattery, Shoichiro Tsugane, Emily White, Yong Bing Xiang, Brent W. Zanke, Wei Zheng, Loic Le Marchand, Graham Casey, Stephen B. Gruber, Ulrike Peters

Research output: Contribution to journal › Article › peer-review

118 Scopus citations

Abstract

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.

Original language	English (US)
Article number	7138
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8138
State	Published - Jul 7 2015
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms8138

Cite this

Schumacher, F. R., Schmit, S. L., Jiao, S., Edlund, C. K., Wang, H., Zhang, B., Hsu, L., Huang, S. C., Fischer, C. P., Harju, J. F., Idos, G. E., Lejbkowicz, F., Manion, F. J., McDonnell, K., McNeil, C. E., Melas, M., Rennert, H. S., Shi, W., Thomas, D. C., ... Peters, U. (2015). Genome-wide association study of colorectal cancer identifies six new susceptibility loci. Nature communications, 6, [7138]. https://doi.org/10.1038/ncomms8138

Schumacher, FR, Schmit, SL, Jiao, S, Edlund, CK, Wang, H, Zhang, B, Hsu, L, Huang, SC, Fischer, CP, Harju, JF, Idos, GE, Lejbkowicz, F, Manion, FJ, McDonnell, K, McNeil, CE, Melas, M, Rennert, HS, Shi, W, Thomas, DC, Van Den Berg, DJ, Hutter, CM, Aragaki, AK, Butterbach, K, Caan, BJ, Carlson, CS, Chanock, SJ, Curtis, KR, Fuchs, CS, Gala, M, Giocannucci, EL, Gogarten, SM, Hayes, RB, Henderson, B, Hunter, DJ, Jackson, RD, Kolonel, LN, Kooperberg, C, Kury, S, Lacroix, A, Laurie, CC, Laurie, CA, Lemire, M, Levine, D, Ma, J, Makar, KW, Qu, C, Taverna, D, Ulrich, CM, Wu, K, Kono, S, West, DW, Berndt, SI, Bezieau, S, Brenner, H, Campbell, PT, Chan, AT, Chang-Claude, J, Coetzee, GA, Conti, DV, Duggan, D, Figueiredo, JC, Fortini, BK, Gallinger, SJ, Gauderman, WJ, Giles, G, Green, R, Haile, R, Harrison, TA, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jacobs, E, Iwasaki, M, Jee, SH, Jenkins, M, Jia, WH, Joshi, A, Li, L, Lindor, NM, Matsuo, K, Moreno, V, Mukherjee, B, Newcomb, PA, Potter, JD, Raskin, L, Rennert, G, Rosse, S, Severi, G, Schoen, RE, Seminara, D, Shu, XO, Slattery, ML, Tsugane, S, White, E, Xiang, YB, Zanke, BW, Zheng, W, Le Marchand, L, Casey, G, Gruber, SB & Peters, U 2015, 'Genome-wide association study of colorectal cancer identifies six new susceptibility loci', Nature communications, vol. 6, 7138. https://doi.org/10.1038/ncomms8138

@article{c97b7624f1b24ad2b885480a78cc9431,

title = "Genome-wide association study of colorectal cancer identifies six new susceptibility loci",

abstract = "Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.",

author = "Schumacher, {Fredrick R.} and Schmit, {Stephanie L.} and Shuo Jiao and Edlund, {Christopher K.} and Hansong Wang and Ben Zhang and Li Hsu and Huang, {Shu Chen} and Fischer, {Christopher P.} and Harju, {John F.} and Idos, {Gregory E.} and Flavio Lejbkowicz and Manion, {Frank J.} and Kevin McDonnell and McNeil, {Caroline E.} and Marilena Melas and Rennert, {Hedy S.} and Wei Shi and Thomas, {Duncan C.} and {Van Den Berg}, {David J.} and Hutter, {Carolyn M.} and Aragaki, {Aaron K.} and Katja Butterbach and Caan, {Bette J.} and Carlson, {Christopher S.} and Chanock, {Stephen J.} and Curtis, {Keith R.} and Fuchs, {Charles S.} and Manish Gala and Giocannucci, {Edward L.} and Gogarten, {Stephanie M.} and Hayes, {Richard B.} and Brian Henderson and Hunter, {David J.} and Jackson, {Rebecca D.} and Kolonel, {Laurence N.} and Charles Kooperberg and Sebastian Kury and Andrea Lacroix and Laurie, {Cathy C.} and Laurie, {Cecelia A.} and Mathiew Lemire and David Levine and Jing Ma and Makar, {Karen W.} and Conghui Qu and Darin Taverna and Ulrich, {Cornelia M.} and Kana Wu and Suminori Kono and West, {Dee W.} and Berndt, {Sonja I.} and Stephane Bezieau and Hermann Brenner and Campbell, {Peter T.} and Chan, {Andrew T.} and Jenny Chang-Claude and Coetzee, {Gerhard A.} and Conti, {David V.} and David Duggan and Figueiredo, {Jane C.} and Fortini, {Barbara K.} and Gallinger, {Steven J.} and Gauderman, {W. James} and Graham Giles and Roger Green and Robert Haile and Harrison, {Tabitha A.} and Michael Hoffmeister and Hopper, {John L.} and Hudson, {Thomas J.} and Eric Jacobs and Motoki Iwasaki and Jee, {Sun Ha} and Mark Jenkins and Jia, {Wei Hua} and Amit Joshi and Li Li and Lindor, {Noralene M.} and Keitaro Matsuo and Victor Moreno and Bhramar Mukherjee and Newcomb, {Polly A.} and Potter, {John D.} and Leon Raskin and Gad Rennert and Stephanie Rosse and Gianluca Severi and Schoen, {Robert E.} and Daniela Seminara and Shu, {Xiao Ou} and Slattery, {Martha L.} and Shoichiro Tsugane and Emily White and Xiang, {Yong Bing} and Zanke, {Brent W.} and Wei Zheng and {Le Marchand}, Loic and Graham Casey and Gruber, {Stephen B.} and Ulrike Peters",

note = "Funding Information: CORECT: this work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-09-002, NIH/NCI U19 CA148107. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CORECT consortium, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CORECT Consortium. ASTERISK: we are very grateful to Dr Bruno Buecher without whom this project would not have existed. We also thank all those who agreed to participate in this study, including the patients and the healthy control persons, as well as all the physicians, technicians and students. DACHS: we thank all participants and cooperating clinicians, and Ute Handte-Daub, Renate Hettler-Jensen, Utz Benscheid, Muhabbet Celik and Ursula Eilber for excellent technical assistance. GECCO: we thank all those at the GECCO Coordinating Center for helping bring together the data and people that made this project possible. HPFS, NHS and PHS: we acknowledge Patrice Soule and Hardeep Ranu of the Dana-Farber Harvard Cancer Center High-Throughput Polymorphism Core who assisted in the genotyping for NHS, HPFS and PHS under the supervision of Dr Immaculata Devivo and Dr David Hunter, Qin (Carolyn) Guo and Lixue Zhu who assisted in programming for NHS and HPFS and Haiyan Zhang who assisted in programming for the PHS. We thank the participants and staff of the Nurses{\textquoteright} Health Study and the Health Professionals Follow-Up Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. We assume full responsibility for analyses and interpretation of these data. PLCO: we thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff or the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information Management Services Inc., Ms Barbara O{\textquoteright}Brien and staff, Westat Inc. and Drs Bill Kopp, Wen Shao and staff, SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions for making this study possible. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI. PMH: we thank the study participants and staff of the Hormones and Colon Cancer study. WHI: we thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://cleo.whi.org/researchers/ Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf. ACC: we thank all study participants and research staff of all studies for their contributions and commitment to this project, Regina Courtney for DNA preparation and Jing He for data processing. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = jul,

day = "7",

doi = "10.1038/ncomms8138",

language = "English (US)",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Genome-wide association study of colorectal cancer identifies six new susceptibility loci

AU - Schumacher, Fredrick R.

AU - Schmit, Stephanie L.

AU - Jiao, Shuo

AU - Edlund, Christopher K.

AU - Wang, Hansong

AU - Zhang, Ben

AU - Hsu, Li

AU - Huang, Shu Chen

AU - Fischer, Christopher P.

AU - Harju, John F.

AU - Idos, Gregory E.

AU - Lejbkowicz, Flavio

AU - Manion, Frank J.

AU - McDonnell, Kevin

AU - McNeil, Caroline E.

AU - Melas, Marilena

AU - Rennert, Hedy S.

AU - Shi, Wei

AU - Thomas, Duncan C.

AU - Van Den Berg, David J.

AU - Hutter, Carolyn M.

AU - Aragaki, Aaron K.

AU - Butterbach, Katja

AU - Caan, Bette J.

AU - Carlson, Christopher S.

AU - Chanock, Stephen J.

AU - Curtis, Keith R.

AU - Fuchs, Charles S.

AU - Gala, Manish

AU - Giocannucci, Edward L.

AU - Gogarten, Stephanie M.

AU - Hayes, Richard B.

AU - Henderson, Brian

AU - Hunter, David J.

AU - Jackson, Rebecca D.

AU - Kolonel, Laurence N.

AU - Kooperberg, Charles

AU - Kury, Sebastian

AU - Lacroix, Andrea

AU - Laurie, Cathy C.

AU - Laurie, Cecelia A.

AU - Lemire, Mathiew

AU - Levine, David

AU - Ma, Jing

AU - Makar, Karen W.

AU - Qu, Conghui

AU - Taverna, Darin

AU - Ulrich, Cornelia M.

AU - Wu, Kana

AU - Kono, Suminori

AU - West, Dee W.

AU - Berndt, Sonja I.

AU - Bezieau, Stephane

AU - Brenner, Hermann

AU - Campbell, Peter T.

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Coetzee, Gerhard A.

AU - Conti, David V.

AU - Duggan, David

AU - Figueiredo, Jane C.

AU - Fortini, Barbara K.

AU - Gallinger, Steven J.

AU - Gauderman, W. James

AU - Giles, Graham

AU - Green, Roger

AU - Haile, Robert

AU - Harrison, Tabitha A.

AU - Hoffmeister, Michael

AU - Hopper, John L.

AU - Hudson, Thomas J.

AU - Jacobs, Eric

AU - Iwasaki, Motoki

AU - Jee, Sun Ha

AU - Jenkins, Mark

AU - Jia, Wei Hua

AU - Joshi, Amit

AU - Li, Li

AU - Lindor, Noralene M.

AU - Matsuo, Keitaro

AU - Moreno, Victor

AU - Mukherjee, Bhramar

AU - Newcomb, Polly A.

AU - Potter, John D.

AU - Raskin, Leon

AU - Rennert, Gad

AU - Rosse, Stephanie

AU - Severi, Gianluca

AU - Schoen, Robert E.

AU - Seminara, Daniela

AU - Shu, Xiao Ou

AU - Slattery, Martha L.

AU - Tsugane, Shoichiro

AU - White, Emily

AU - Xiang, Yong Bing

AU - Zanke, Brent W.

AU - Zheng, Wei

AU - Le Marchand, Loic

AU - Casey, Graham

AU - Gruber, Stephen B.

AU - Peters, Ulrike

N1 - Funding Information: CORECT: this work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-09-002, NIH/NCI U19 CA148107. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CORECT consortium, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CORECT Consortium. ASTERISK: we are very grateful to Dr Bruno Buecher without whom this project would not have existed. We also thank all those who agreed to participate in this study, including the patients and the healthy control persons, as well as all the physicians, technicians and students. DACHS: we thank all participants and cooperating clinicians, and Ute Handte-Daub, Renate Hettler-Jensen, Utz Benscheid, Muhabbet Celik and Ursula Eilber for excellent technical assistance. GECCO: we thank all those at the GECCO Coordinating Center for helping bring together the data and people that made this project possible. HPFS, NHS and PHS: we acknowledge Patrice Soule and Hardeep Ranu of the Dana-Farber Harvard Cancer Center High-Throughput Polymorphism Core who assisted in the genotyping for NHS, HPFS and PHS under the supervision of Dr Immaculata Devivo and Dr David Hunter, Qin (Carolyn) Guo and Lixue Zhu who assisted in programming for NHS and HPFS and Haiyan Zhang who assisted in programming for the PHS. We thank the participants and staff of the Nurses’ Health Study and the Health Professionals Follow-Up Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. We assume full responsibility for analyses and interpretation of these data. PLCO: we thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff or the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information Management Services Inc., Ms Barbara O’Brien and staff, Westat Inc. and Drs Bill Kopp, Wen Shao and staff, SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions for making this study possible. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI. PMH: we thank the study participants and staff of the Hormones and Colon Cancer study. WHI: we thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://cleo.whi.org/researchers/ Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf. ACC: we thank all study participants and research staff of all studies for their contributions and commitment to this project, Regina Courtney for DNA preparation and Jing He for data processing. Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2015/7/7

Y1 - 2015/7/7

N2 - Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.

AB - Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.

UR - http://www.scopus.com/inward/record.url?scp=84936745391&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936745391&partnerID=8YFLogxK

U2 - 10.1038/ncomms8138

DO - 10.1038/ncomms8138

M3 - Article

C2 - 26151821

AN - SCOPUS:84936745391

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 7138

ER -

Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this