Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles British Journal of Cancer Year : 2020

Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function

Abstract

Background Genome-wide association studies (GWASes) have identified many noncoding germline single-nucleotide polymorphisms (SNPs) that are associated with an increased risk of developing cancer. However, how these SNPs affect cancer risk is still largely unknown. Methods We used a systems biology approach to analyse the regulatory role of cancer-risk SNPs in thirteen tissues. By using data from the Genotype-Tissue Expression (GTEx) project, we performed an expression quantitative trait locus (eQTL) analysis. We represented both significant cis- and trans-eQTLs as edges in tissue-specific eQTL bipartite networks. Results Each tissue-specific eQTL network is organised into communities that group sets of SNPs and functionally related genes. When mapping cancer-risk SNPs to these networks, we find that in each tissue, these SNPs are significantly overrepresented in communities enriched for immune response processes, as well as tissue-specific functions. Moreover, cancer-risk SNPs are more likely to be 'cores' of their communities, influencing the expression of many genes within the same biological processes. Finally, cancer-risk SNPs preferentially target oncogenes and tumour-suppressor genes, suggesting that they may alter the expression of these key cancer genes. Conclusions This approach provides a new way of understanding genetic effects on cancer risk and provides a biological context for interpreting the results of GWAS cancer studies.
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hal-02964020 , version 1 (14-12-2023)

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Maud Fagny, John Platig, Marieke Lydia Kuijjer, Xihong Lin, John Quackenbush. Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function. British Journal of Cancer, 2020, 122 (4), pp.569-577. ⟨10.1038/s41416-019-0614-3⟩. ⟨hal-02964020⟩
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