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ADH1B and ALDH2 are associated with metachronous SCC after endoscopic submucosal dissection of esophageal squamous cell carcinoma.

ABSTRACT: A previous genome-wide association study identified two novel esophageal squamous cell carcinoma (ESCC) susceptibility genes, ADH1B and ALDH2. We investigated the characteristics of ESCC, and the relationship between metachronous esophageal and/or pharyngeal squamous cell carcinoma (SCC) and the ADH1B & ALDH2 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 ADH1B & ALDH2 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 ADH1B and rs671 GA located on ALDH2 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 (LVLs) 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 SCCs 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 SCCs after ESD of ESCC risk approximately nearly 12-fold. Our findings elucidated the crucial role of multiple genetic variations in ADH1B and ALDH2 as biomarkers of metachronous ESCC.

SUBMITTER: Kagemoto K

PROVIDER: S-EPMC4944865 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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ADH1B and ALDH2 are associated with metachronous SCC after endoscopic submucosal dissection of esophageal squamous cell carcinoma.

Kagemoto Kenichi K Urabe Yuji Y Miwata Tomohiro T Oka Shiro S Ochi Hidenori H Kitadai Yasuhiko Y Tanaka Shinji S Chayama Kazuaki K

Cancer medicine 20160331 7

A previous genome-wide association study identified two novel esophageal squamous cell carcinoma (ESCC) susceptibility genes, ADH1B and ALDH2. We investigated the characteristics of ESCC, and the relationship between metachronous esophageal and/or pharyngeal squamous cell carcinoma (SCC) and the ADH1B & ALDH2 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, ...[more]

PMID: 27038040

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Project description:Background There is limited reporting of treatment options for early esophageal squamous cell carcinoma in esophageal-gastric fundal varices patients. Historically, surgery is the preferred treatment for squamous cell carcinoma; however, esophagectomy is associated with higher complications and death rates. The difficulty of such an operation was the varicose veins around the mucosa of the lesion. Possibility of concomitant intraoperative fatal bleeding. Previous studies have proved the effectiveness of endoscopic mucosal resection (EMR) paired with endoscopic injection sclerotherapy (EIS) for treating early esophageal cancers on esophageal varices. Case Description We reported an effective endoscopic treatment of such conditions in a 62-year-old man with liver cirrhosis. After seeking informed consent, we performed endoscopic submucosal dissection (ESD) of early esophageal squamous cell carcinoma after the eradication of esophageal-gastric fundal varices using EIS. The resection margins indicated negative for carcinoma and dysplasia, suggesting that no recurrence and complication occurred. The patient was discharged 5 days after ESD without any complications including perforation or bleeding. No complaint from the patient was received during the 1-week follow-up, and the patient was tolerating solid food. The pathological result of the two lesions both showed moderately differentiated squamous cell carcinoma of the esophagus, T1bN0M0. The resection margins suggested negative for both carcinoma and dysplasia according to pathological examination. There was no recurrence or adverse event during follow-up. Conclusions Our case presented the successful treatment of esophageal squamous cell carcinoma on esophageal-gastric fundal varices. This indicated that patients with cirrhosis and portal hypertension could also be treated with ESD, which could reduce trauma and discomfort and improve their quality of life. We recommend future studies to further investigate the indications of using endoscopic treatment for patients with cirrhosis.

Dataset Information

ADH1B and ALDH2 are associated with metachronous SCC after endoscopic submucosal dissection of esophageal squamous cell carcinoma.

Publications

ADH1B and ALDH2 are associated with metachronous SCC after endoscopic submucosal dissection of esophageal squamous cell carcinoma.

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