Risk SNP-Mediated Enhancer-Promoter Interaction Drives Colorectal Cancer through Both FADS2 and AP002754.2

Cancer Research
Jianbo TianXiaoping Miao

Abstract

Although genome-wide association studies (GWAS) have identified more than 100 colorectal cancer risk loci, most of the biological mechanisms associated with these loci remain unclear. Here we first performed a comprehensive expression quantitative trait loci analysis in colorectal cancer tissues adjusted for multiple confounders to test the determinants of germline variants in established GWAS susceptibility loci on mRNA and long noncoding RNA (lncRNA) expression. Combining integrative functional genomic/epigenomic analyses and a large-scale population study consisting of 6,024 cases and 10,022 controls, we then prioritized rs174575 with a C>G change as a potential causal candidate for colorectal cancer at 11q12.2, as its G allele was associated with an increased risk of colorectal cancer (OR = 1.26; 95% confidence interval = 1.17-1.36; P = 2.57 × 10-9). rs174575 acted as an allele-specific enhancer to distally facilitate expression of both FADS2 and lncRNA AP002754.2 via long-range enhancer-promoter interaction loops, which were mediated by E2F1. AP002754.2 further activated a transcriptional activator that upregulated FADS2 expression. FADS2, in turn, was overexpressed in colorectal cancer tumor tissues and functioned as a po...Continue Reading

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Citations

Jan 8, 2021·Annals of the Rheumatic Diseases·Akari SuzukiKazuhiko Yamamoto
Jul 3, 2021·International Journal of Molecular Sciences·Arina O DegtyarevaTatiana I Merkulova
Jul 3, 2021·International Journal of Molecular Sciences·Jiřina HofmanováJan Vondráček
Aug 31, 2021·World Journal of Gastrointestinal Oncology·Yan-Dong MiaoDeng-Hai Mi
Oct 13, 2021·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Bin LiRong Zhong

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