Open AccessADH 1B and ALDH 2 are associated with metachronous SCC after endoscopic submucosal dissection of esophageal squamous cell carcinoma
Author(s) -
Kagemoto Kenichi,
Urabe Yuji,
Miwata Tomohiro,
Oka Shiro,
Ochi Hidenori,
Kitadai Yasuhiko,
Tanaka Shinji,
Chayama Kazuaki
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.705
Subject(s) - hazard ratio , esophageal squamous cell carcinoma , confidence interval , endoscopic submucosal dissection , gastroenterology , medicine , proportional hazards model , incidence (geometry) , odds ratio , carcinoma , surgery , physics , optics
A previous genome‐wide association study identified two novel esophageal squamous cell carcinoma ( ESCC ) susceptibility genes, ADH 1B and ALDH 2 . We investigated the characteristics of ESCC , and the relationship between metachronous esophageal and/or pharyngeal squamous cell carcinoma ( SCC ) and the ADH 1B & ALDH 2 risk alleles. One hundred and seventeen superficial ESCC patients who underwent treatment with endoscopic submucosal dissection ( ESD ) were followed up using endoscopy for ≥12 months. First, we performed a replication analysis to confirm the relationship between ESCC and the ADH 1B & ALDH 2 risk alleles using 117 superficial ESCC cases and 1125 healthy controls. Next, we investigated the incidence and genetic/environmental factors associated with metachronous SCC development after ESD . We also analyzed the potential risk factors for metachronous SCC development using Cox's proportional hazards model. rs1229984 GG located on ADH 1B and rs671 GA located on ALDH 2 were significantly associated with ESCC progression ( P = 7.93 × 10 −4 and P = 1.04 × 10 −5 ). Patients with rs1229984 GG , those with rs671 GA , smokers, heavy alcohol drinkers (44 g/day ethanol), and presence of multiple Lugol‐voiding lesions ( LVL s) developed metachronous SCC more frequently ( P = 3.20 × 10 −3 , 7.00 × 10 −4 , 4.00 × 10 −4 , 2.15 × 10 −2 , and 4.41 × 10 −3 , respectively), with hazard ratios were 2.84 (95% confidence interval [ CI ] = 1.43–5.63), 4.57 (95% CI = 1.80–15.42), 4.84 (95% CI = 1.89–16.41), and 2.34 (95% CI = 1.12–5.31), respectively. Multiple logistic regression analysis revealed that rs1229984 GG , rs671 GA , and smoking status were independently associated with the risk of developing metachronous SCC s after ESD . Moreover, we found cumulative effects of these two genetic factors (rs1229984 GG and rs671 GA ) and one environmental factor (tobacco smoking) which appear to increase metachrous SCC s after ESD of ESCC risk approximately nearly 12‐fold. Our findings elucidated the crucial role of multiple genetic variations in ADH 1B and ALDH 2 as biomarkers of metachronous ESCC .