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

• Published in: Scientific reports Vol. 11; no. 1; p. 20150
• Main Authors: Onozato, Yusuke, Sasaki, Yu, Abe, Yasuhiko, Sato, Hidenori, Yagi, Makoto, Mizumoto, Naoko, Kon, Takashi, Sakai, Takayuki, Ito, Minami, Umehara, Matsuki, Koseki, Ayumi, Ueno, Yoshiyuki
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.10.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Aged; Alcohol Drinking - trends; Alcohol use; Biomarkers, Tumor - genetics; Drinking behavior; Epithelium; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - pathology; Esophagus; Esophagus - metabolism; Esophagus - pathology; Female; Females; Follow-Up Studies; Gene Expression Profiling; Genomics; Humans; Male; Males; Non-Smokers - statistics & numerical data; Polymorphism, Single Nucleotide; Prognosis; Retrospective Studies; Risk Factors; Smoking; Squamous cell carcinoma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-99790-z

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.