Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer

GAME-ON Network, GECCO, FOCI, CORECT, DRIVE

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

RESULTS: We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003).

CONCLUSIONS: Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer.

BACKGROUND: Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted.

METHODS: We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided.

Original languageEnglish (US)
JournalJournal of the National Cancer Institute
Volume107
Issue number11
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

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Ovarian Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Breast Neoplasms
Inflammation
Neoplasms
Genome-Wide Association Study
cdc Genes
National Cancer Institute (U.S.)
Innate Immunity
Meta-Analysis
Immune System

ASJC Scopus subject areas

  • Medicine(all)

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Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers : Lung, Ovary, Prostate, Breast, and Colorectal Cancer. / GAME-ON Network; GECCO; FOCI; CORECT; DRIVE.

In: Journal of the National Cancer Institute, Vol. 107, No. 11, 01.11.2015.

Research output: Contribution to journalArticle

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title = "Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer",
abstract = "RESULTS: We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003).CONCLUSIONS: Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer.BACKGROUND: Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted.METHODS: We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided.",
author = "{GAME-ON Network} and GECCO and FOCI and CORECT and DRIVE and Hung, {Rayjean J.} and Ulrich, {Cornelia M.} and Goode, {Ellen L} and Yonathan Brhane and Kenneth Muir and Chan, {Andrew T.} and Marchand, {Loic L e} and Joellen Schildkraut and Witte, {John S.} and Rosalind Eeles and Paolo Boffetta and Spitz, {Margaret R.} and Poirier, {Julia G.} and Rider, {David N.} and Fridley, {Brooke L.} and Zhihua Chen and Christopher Haiman and Fredrick Schumacher and Easton, {Douglas F.} and Landi, {Maria T eresa} and Paul Brennan and Richard Houlston and Christiani, {David C.} and Field, {John K.} and Heike Bickeb{\"o}ller and Angela Risch and Zsofia Kote-Jarai and Fredrik Wiklund and Henrik Gr{\"o}nberg and Stephen Chanock and Berndt, {Sonja I.} and Peter Kraft and Sara Lindstr{\"o}m and {Al Olama}, {Ali A min} and Honglin Song and Catherine Phelan and Nicholas Wentzensen and Ulrike Peters and Slattery, {Martha L.} and Sellers, {Thomas A.} and Graham Casey and Gruber, {Stephen B.} and Hunter, {David J.} and Amos, {Christopher I.} and Brian Henderson",
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TY - JOUR

T1 - Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers

T2 - Lung, Ovary, Prostate, Breast, and Colorectal Cancer

AU - GAME-ON Network

AU - GECCO

AU - FOCI

AU - CORECT

AU - DRIVE

AU - Hung, Rayjean J.

AU - Ulrich, Cornelia M.

AU - Goode, Ellen L

AU - Brhane, Yonathan

AU - Muir, Kenneth

AU - Chan, Andrew T.

AU - Marchand, Loic L e

AU - Schildkraut, Joellen

AU - Witte, John S.

AU - Eeles, Rosalind

AU - Boffetta, Paolo

AU - Spitz, Margaret R.

AU - Poirier, Julia G.

AU - Rider, David N.

AU - Fridley, Brooke L.

AU - Chen, Zhihua

AU - Haiman, Christopher

AU - Schumacher, Fredrick

AU - Easton, Douglas F.

AU - Landi, Maria T eresa

AU - Brennan, Paul

AU - Houlston, Richard

AU - Christiani, David C.

AU - Field, John K.

AU - Bickeböller, Heike

AU - Risch, Angela

AU - Kote-Jarai, Zsofia

AU - Wiklund, Fredrik

AU - Grönberg, Henrik

AU - Chanock, Stephen

AU - Berndt, Sonja I.

AU - Kraft, Peter

AU - Lindström, Sara

AU - Al Olama, Ali A min

AU - Song, Honglin

AU - Phelan, Catherine

AU - Wentzensen, Nicholas

AU - Peters, Ulrike

AU - Slattery, Martha L.

AU - Sellers, Thomas A.

AU - Casey, Graham

AU - Gruber, Stephen B.

AU - Hunter, David J.

AU - Amos, Christopher I.

AU - Henderson, Brian

PY - 2015/11/1

Y1 - 2015/11/1

N2 - RESULTS: We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003).CONCLUSIONS: Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer.BACKGROUND: Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted.METHODS: We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided.

AB - RESULTS: We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003).CONCLUSIONS: Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer.BACKGROUND: Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted.METHODS: We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided.

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U2 - 10.1093/jnci/djv246

DO - 10.1093/jnci/djv246

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