Open AccessAreca nut is associated with younger age of diagnosis, poor chemoradiotherapy response, and shorter overall survival in esophageal squamous cell carcinoma
Author(s) -
ChangHan Chen,
Hung-I Lu,
Yu Ming Wang,
YenHao Chen,
Chien-Ming Lo,
WanTing Huang,
Shau-Hsuan Li
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0172752
Subject(s) - areca , medicine , esophageal squamous cell carcinoma , chemoradiotherapy , oncology , esophageal cancer , young adult , carcinoma , nut , overall survival , cancer , engineering , structural engineering
Objective Areca nut chewing is carcinogenic to humans. However, little is known about the impact of areca nut chewing on esophageal squamous cell carcinoma (ESCC). Methods We retrospectively reviewed 286 ESCC patients who received surgery or preoperative chemoradiotherapy followed by surgery at our institution. Background characteristics including areca nut chewing history were analyzed. The 4-nitroquinoline 1-oxide (4-NQO)-induced murine ESCC model was used to test the impact of arecoline, a main constituent of areca nut, on ESCC. Results Compared to patients without areca nut chewing history, patients with areca nut chewing history had overall a younger age of onset (Mean age: 56.75 versus 52.68 yrs, P<0.001) and significantly worse overall survival than those without areca nut chewing history (P = 0.026). Among patients who received surgery, the overall survival rates were not significantly different between those with or without areca nut chewing history. Among patients who received preoperative chemoradiotherapy followed by surgery, those with areca nut chewing history had a significantly lower pathologic complete response rate (P = 0.002) and lower overall survival rate (P = 0.002) than those without. In the murine ESCC model, the incidence of esophageal invasive squamous cell carcinoma was 40% in mice exposed to concomitant 4-NQO and arecoline treatment for 8 weeks and 6% in mice exposed to 4-NQO only for 8 weeks (P = 0.037). Conclusions Our results indicate that areca nut chewing history is significantly associated with younger age of onset, poor response to chemoradiotherapy, and shorter overall survival in ESCC patients. Arecoline, a main constituent of areca nut, accelerates esophageal tumorigenesis in the 4-NQO-induced murine ESCC model.