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Multitrait GWAS and functional validation reveal genetic loci for gastric cancer - PubMed

4 hours ago
  • #GWAS
  • #Genetic Loci
  • #Gastric Cancer
  • Gastric cancer is a leading cause of cancer-related death, especially in East Asia.
  • Genome-wide association study (GWAS) data from BioBank Japan reveals shared genetic associations between gastric cancer and 25 other phenotypes, notably cardiovascular conditions like angina pectoris and myocardial infarction.
  • Mendelian randomization supports a causal relationship between these traits and gastric cancer risk.
  • Multitrait GWAS analysis identifies a novel pleiotropic locus at 12q22 (rs12814712), shared between gastric cancer and cardiovascular traits.
  • Functional experiments show the risk allele at rs12814712 reduces transcriptional activity and downregulates nearby genes, particularly VEZT.
  • Overexpression of VEZT and NR2C1 in gastric cancer cells suppresses proliferation and migration, while their knockdown promotes malignancy.
  • The study highlights rs12814712 as a novel susceptibility locus for gastric cancer and its regulatory role in disease-related gene networks.