Research Papers:

Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma

Xin Li _, Liming Liang, Immaculata De Vivo, Jean Y. Tang and Jiali Han

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Oncotarget. 2016; 7:36885-36895. https://doi.org/10.18632/oncotarget.9212

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Xin Li1, Liming Liang1, Immaculata De Vivo1,2, Jean Y. Tang3, Jiali Han4

1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

2Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

3Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA

4Department of Epidemiology, Fairbanks School of Public Health, Indiana University, and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA

Correspondence to:

Jiali Han, e-mail: [email protected]

Keywords: expression-related SNPs (eSNPs), pathway analysis, basal cell carcinoma (BCC), genome-wide association study (GWAS), pathway databases

Received: November 10, 2015     Accepted: April 24, 2016     Published: May 6, 2016


Genome-wide association studies (GWASs) have primarily focused on the association between individual genetic markers and risk of disease. We applied a novel approach that integrates skin expression-related single-nucleotide polymorphisms (eSNPs) and pathway analysis for GWAS of basal cell carcinoma (BCC) to identify potential novel biological pathways. We evaluated the associations between 70,932 skin eSNPs and risk of BCC among 2,323 cases and 7,275 controls of European ancestry, and then assigned them to the pathways defined by KEGG, GO, and BioCarta databases. Three KEGG pathways (colorectal cancer, actin cytoskeleton, and BCC), two GO pathways (cellular component disassembly in apoptosis, and nucleus organization), and four BioCarta pathways (Ras signaling, T cell receptor signaling, natural killer cell-mediated cytotoxicity, and links between Pyk2 and Map Kinases) showed significant association with BCC risk with p-value<0.05 and FDR<0.2. These pathways also ranked at top in sensitivity analyses. Two positive controls in KEGG, the hedgehog pathway and the BCC pathway, showed significant association with BCC risk in both main and sensitivity analyses. Our results indicate that SNPs that are undetectable by conventional GWASs are significantly associated with BCC when tested as pathways. Biological studies of these gene groups suggest their potential roles in the etiology of BCC.

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