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

Colorectal Transdisciplinary (CORECT) Study, Ovarian Cancer Association Consortium (OCAC), The PRACTICAL Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), African American Breast Cancer Consortium (AABC), African Ancestry Prostate Cancer Consortium (AAPC)

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)5103-5114
Number of pages12
JournalCancer Research
Volume76
Issue number17
DOIs
StatePublished - Sep 1 2016

Fingerprint

Ovarian Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Genome
Breast Neoplasms
Lung
Breast
Neoplasms
Genome-Wide Association Study
Squamous Cell Carcinoma
Gene Expression
Adenocarcinoma of lung

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Colorectal Transdisciplinary (CORECT) Study, Ovarian Cancer Association Consortium (OCAC), The PRACTICAL Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), African American Breast Cancer Consortium (AABC), & African Ancestry Prostate Cancer Consortium (AAPC) (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

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations. / Colorectal Transdisciplinary (CORECT) Study; Ovarian Cancer Association Consortium (OCAC); The PRACTICAL Consortium; Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON); African American Breast Cancer Consortium (AABC); African Ancestry Prostate Cancer Consortium (AAPC).

In: Cancer Research, Vol. 76, No. 17, 01.09.2016, p. 5103-5114.

Research output: Contribution to journalArticle

Colorectal Transdisciplinary (CORECT) Study, Ovarian Cancer Association Consortium (OCAC), The PRACTICAL Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), African American Breast Cancer Consortium (AABC) & African Ancestry Prostate Cancer Consortium (AAPC) 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
Colorectal Transdisciplinary (CORECT) Study, Ovarian Cancer Association Consortium (OCAC), The PRACTICAL Consortium, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), African American Breast Cancer Consortium (AABC), African Ancestry Prostate Cancer Consortium (AAPC). Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations. Cancer Research. 2016 Sep 1;76(17):5103-5114. https://doi.org/10.1158/0008-5472.CAN-15-2980
Colorectal Transdisciplinary (CORECT) Study ; Ovarian Cancer Association Consortium (OCAC) ; The PRACTICAL Consortium ; Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) ; African American Breast Cancer Consortium (AABC) ; African Ancestry Prostate Cancer Consortium (AAPC). / Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations. In: Cancer Research. 2016 ; Vol. 76, No. 17. pp. 5103-5114.
@article{4c92be6044c8479da9b2f988a33a266d,
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 = "{Colorectal Transdisciplinary (CORECT) Study} and {Ovarian Cancer Association Consortium (OCAC)} and {The PRACTICAL Consortium} and {Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)} and {African American Breast Cancer Consortium (AABC)} and {African Ancestry Prostate Cancer Consortium (AAPC)} and 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 Lindor, {Noralane Morey} and Thibodeau, {Stephen N}",
year = "2016",
month = "9",
day = "1",
doi = "10.1158/0008-5472.CAN-15-2980",
language = "English (US)",
volume = "76",
pages = "5103--5114",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "17",

}

TY - JOUR

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

AU - Colorectal Transdisciplinary (CORECT) Study

AU - Ovarian Cancer Association Consortium (OCAC)

AU - The PRACTICAL Consortium

AU - Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)

AU - African American Breast Cancer Consortium (AABC)

AU - African Ancestry Prostate Cancer Consortium (AAPC)

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 - Lindor, Noralane Morey

AU - Thibodeau, Stephen N

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 - http://www.scopus.com/inward/record.url?scp=84986888945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986888945&partnerID=8YFLogxK

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

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

M3 - Article

C2 - 27197191

AN - SCOPUS:84986888945

VL - 76

SP - 5103

EP - 5114

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 17

ER -