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

Publication ,  Journal Article
Hung, RJ; Ulrich, CM; Goode, EL; Brhane, Y; Muir, K; Chan, AT; Marchand, LL; Schildkraut, J; Witte, JS; Eeles, R; Boffetta, P; Spitz, MR ...
Published in: J Natl Cancer Inst
November 2015

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. 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.

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Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

November 2015

Volume

107

Issue

11

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proteins
  • Prostatic Neoplasms
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Male
  • Lung Neoplasms
  • Intracellular Signaling Peptides and Proteins
  • Inflammation
  • Humans
 

Citation

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Hung, R. J., Ulrich, C. M., Goode, E. L., Brhane, Y., Muir, K., Chan, A. T., … GAME-ON Network, . (2015). Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer. J Natl Cancer Inst, 107(11). https://doi.org/10.1093/jnci/djv246
Hung, Rayjean J., Cornelia M. Ulrich, Ellen L. Goode, Yonathan Brhane, Kenneth Muir, Andrew T. Chan, Loic Le Marchand, et al. “Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.J Natl Cancer Inst 107, no. 11 (November 2015). https://doi.org/10.1093/jnci/djv246.
Hung RJ, Ulrich CM, Goode EL, Brhane Y, Muir K, Chan AT, et al. Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer. J Natl Cancer Inst. 2015 Nov;107(11).
Hung, Rayjean J., et al. “Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.J Natl Cancer Inst, vol. 107, no. 11, Nov. 2015. Pubmed, doi:10.1093/jnci/djv246.
Hung RJ, Ulrich CM, Goode EL, Brhane Y, Muir K, Chan AT, Marchand LL, Schildkraut J, Witte JS, Eeles R, Boffetta P, Spitz MR, Poirier JG, Rider DN, Fridley BL, Chen Z, Haiman C, Schumacher F, Easton DF, Landi MT, Brennan P, Houlston R, Christiani DC, Field JK, Bickeböller H, Risch A, Kote-Jarai Z, Wiklund F, Grönberg H, Chanock S, Berndt SI, Kraft P, Lindström S, Al Olama AA, Song H, Phelan C, Wentzensen N, Peters U, Slattery ML, GECCO, Sellers TA, FOCI, Casey G, Gruber SB, CORECT, Hunter DJ, DRIVE, Amos CI, Henderson B, GAME-ON Network. Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer. J Natl Cancer Inst. 2015 Nov;107(11).
Journal cover image

Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

November 2015

Volume

107

Issue

11

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proteins
  • Prostatic Neoplasms
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Male
  • Lung Neoplasms
  • Intracellular Signaling Peptides and Proteins
  • Inflammation
  • Humans