In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 6, No. 21 ( 2020-05-22)
Abstract:
The biological effects of susceptibility loci are rarely reported in gastric tumorigenesis. We conducted a large-scale cross-ancestry genetic study in 18,852 individuals and identified the potential causal variant rs3850997 T 〉 G at 16p13 significantly associated with a decreased risk of gastric cancer [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.83 to 0.91, P = 2.13 × 10 −9 ]. This risk effect was mediated through the mapped long noncoding RNA GCLET ( Gastric Cancer Low-Expressed Transcript ; OR indirect = 0.987, 95% CI = 0.975 to 0.999, P = 0.018). Mechanistically, rs3850997 exerted an allele-specific long-range regulatory effect on GCLET by affecting the binding affinity of CTCF. Furthermore, GCLET increased FOXP2 expression by competing with miR-27a-3p, and this regulation remarkably affected in vitro, in vivo, and clinical gastric cancer phenotypes. The findings highlight the genetic functions and implications for the etiology and pathology of cancers.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.aay5525
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
detail.hit.zdb_id:
2810933-8
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