Back to Search
Start Over
Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer
- Source :
- Journal of the National Cancer Institute. 107(11)
- Publication Year :
- 2014
-
Abstract
- 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. © The Author 2015. Published by Oxford University Press. All rights reserved.
- Subjects :
- Oncology
Male
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Colorectal cancer
Genome-wide association study
Breast Neoplasms
Disease
Mouse model of colorectal and intestinal cancer
Biology
Article
Breast cancer
Prostate
Internal medicine
medicine
Humans
Lung cancer
Adaptor Proteins, Signal Transducing
Inflammation
Ovarian Neoplasms
Lung, ovary, prostate, breast, and colorectal cancer
Intracellular Signaling Peptides and Proteins
Prostatic Neoplasms
Proteins
medicine.disease
3. Good health
medicine.anatomical_structure
Female
Ovarian cancer
Colorectal Neoplasms
Genome-Wide Association Study
Signal Transduction
Subjects
Details
- ISSN :
- 14602105
- Volume :
- 107
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of the National Cancer Institute
- Accession number :
- edsair.doi.dedup.....c6da352f7f0e292600b42323fb2c0e2b