Familial Esophageal Squamous Cell Carcinoma with damaging rare/germline mutations in KCNJ12/KCNJ18 and GPRIN2 genes

Cancer Genet. 2018 Feb;221:46-52. doi: 10.1016/j.cancergen.2017.11.011. Epub 2017 Dec 23.


In Iran, esophageal cancer is the fourth common cancers in women and sixth common cancers in men. Here we evaluated the importance of familial risk factors and the role of genetic predisposition in Esophageal Squamous Cell Carcinoma (ESCC) using Whole-Exome Sequencing (WES). Germline damaging mutations were identified in WES data from 9 probands of 9 unrelated ESCC pedigrees. Mutations were confirmed with Sanger sequencing and evaluated amplification-refractory mutation system-Polymerase Chain Reaction (ARMS-PCR) in 50 non-related ethnically matched samples and in complete genomics database. Sixteen candidate variants were detected in ESCC 9 probands. Four of these 16 variants were rare damaging mutations including novel mutations in KCNJ12/KCNJ18, and GPRIN2 genes. This WES study in Iranian patients with ESCC, provides insight into the identification of novel germline mutations in familial ESCC. Our data suggest an association between specific mutations and increased risk of ESCC.

Keywords: Familial Esophageal Squamous Cell Carcinoma; Whole-Exome Sequencing; environmental factor; genetic predisposition; germline mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Potassium Channels, Inwardly Rectifying / metabolism


  • Carrier Proteins
  • GPRIN2 protein, human
  • KCNJ18 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Potassium Channels, Inwardly Rectifying