Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females

Sci Rep. 2021 Oct 11;11(1):20150. doi: 10.1038/s41598-021-99790-z.

Abstract

Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n = 117) were drinkers or smokers, whereas 45% of the female patients (n = 33) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alcohol Drinking / trends*
  • Biomarkers, Tumor / genetics*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Esophagus / metabolism
  • Esophagus / pathology*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Genomics
  • Humans
  • Male
  • Non-Smokers / statistics & numerical data*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Retrospective Studies
  • Risk Factors

Substances

  • Biomarkers, Tumor