Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study

Chikatoshi Katada; Tetsuji Yokoyama; Tomonori Yano; Yasuaki Furue; Haruhisa Suzuki; Kenji Ishido; Keiko Yamamoto; Hiroyoshi Nakanishi; Tomoyuki Koike; Masashi Tamaoki; Noboru Kawata; Motohiro Hirao; Yoshiro Kawahara; Takashi Ogata; Atsushi Katagiri; Takenori Yamanouchi; Hirofumi Kiyokawa; Hirofumi Kawakubo; Maki Konno; Akira Yokoyama; Shinya Ohashi; Tai Omori; Tadakazu Shimoda; Atsushi Ochiai; Hideki Ishikawa; Akira Yokoyama; Manabu Muto; Japan Esophageal Cohort Study Group

doi:10.1016/j.lanwpc.2026.101798

Alcohol consumption, smoking, and the implications of their cessations for field carcinogenesis in the esophagus: a 10-year prospective cohort study

Lancet Reg Health West Pac. 2026 Jan 20:67:101798. doi: 10.1016/j.lanwpc.2026.101798. eCollection 2026 Feb.

Authors

Chikatoshi Katada¹, Tetsuji Yokoyama², Tomonori Yano³, Yasuaki Furue⁴, Haruhisa Suzuki^{5

6}, Kenji Ishido⁷, Keiko Yamamoto⁸, Hiroyoshi Nakanishi⁹, Tomoyuki Koike¹⁰, Masashi Tamaoki¹, Noboru Kawata¹¹, Motohiro Hirao¹², Yoshiro Kawahara¹³, Takashi Ogata¹⁴, Atsushi Katagiri¹⁵, Takenori Yamanouchi¹⁶, Hirofumi Kiyokawa¹⁷, Hirofumi Kawakubo¹⁸, Maki Konno¹⁹, Akira Yokoyama¹, Shinya Ohashi¹, Tai Omori¹⁸, Tadakazu Shimoda²⁰, Atsushi Ochiai²¹, Hideki Ishikawa²², Akira Yokoyama²³, Manabu Muto¹; Japan Esophageal Cohort Study Group

Collaborators

Japan Esophageal Cohort Study Group:
Keisuke Hori, Hiroyuki Okada, Takeshi Shinozaki, Keiko Minashi, Yasumasa Matsuo, Takashi Tsuda, Yuichi Shimizu, Satoshi Abiko, Kohei Takizawa, Naomi Kakushima, Noriaki Hasuike, Takako Yoshii, Norisuke Nakayama, Nozomu Kobayashi, Hisashi Doyama, Kenichi Takemura, Masahiro Saito, Ichiro Oda, Satoru Nonaka, Yasumasa Ezoe, Yutaro Kubota, Kazuo Konishi, Satoshi Tanabe, Toshimasa Tsujinaka, Toshiyuki Yoshio

Affiliations

¹ Department of Medical Oncology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan.
² Department of Health Promotion, National Institute of Public Health, 2-3-6 Minami, Wako, Saitama, 351-0197, Japan.
³ Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan.
⁴ Department of Endoscopy, Saitama Cancer Center, 780, Kitaadachi-gun, Saitama, 362-0806, Japan.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
⁶ Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
⁷ Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa, 252-0375, Japan.
⁸ Division of Endoscopy, Hokkaido University Hospital, Kita 14 jo, Nishi 5 chome, Kitaku, Sapporo, 060-8648, Japan.
⁹ Department of Gastroenterology, Ishikawa Prefectural Central Hospital, 2-1 Kuratsuki-Higashi, Kanazawa, Ishikawa, 920-8530, Japan.
¹⁰ Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
¹¹ Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumicho, Suntougun, Shizuoka, 411-8777, Japan.
¹² Department of Surgery, NHO Osaka National Hospital, 2-1-14 Hoenzaka, Tyuoku, Osaka, 540-0006, Japan.
¹³ Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
¹⁴ Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
¹⁵ Division of Gastroenterology, Department of Medicine, Showa Medical University Hospital, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
¹⁶ Department of Gastroenterology, Kumamoto Regional Medical Center, 5-16-10 Honjyo, Tyuuou, Kumamoto, 860-0811, Japan.
¹⁷ Department of Gastroenterology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.
¹⁸ Department of Surgery, Kawasaki Municipal Kawasaki Hospital, 12-1 Sinkawa dori, Kawasaki ku, Kawasaki City, Kanagawa, 210-0013, Japan.
¹⁹ Department of Gastroenterology, Tochigi Cancer Center, 4-9-13 Yonan, Utsunomiya, Tochigi, 320-0834, Japan.
²⁰ Department of Diagnostic Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi -cho, Suntogun, Nagaizumi, 411-8777, Japan.
²¹ Exploratory Oncology Research and Clinicai Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.
²² Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
²³ Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, 5-3-1 Nobi, Yokosuka, Kanagawa, 239-0841, Japan.

Abstract

Background: Alcohol and tobacco are established carcinogens, which promote field carcinogenesis for esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the long-term effects of alcohol and tobacco cessations, and background mucosal status, on risk for metachronous ESCC (mESCC) after endoscopic resection (ER).

Methods: This was a multicentre prospective cohort study of patients with intramucosal ESCC treated by ER. All participants received structured education on cessation, and underwent regular endoscopic surveillance. Patients were stratified by Lugol-voiding lesion (LVL) grade (A: none, B: 1-9, C: ≥10). The impacts of alcohol and smoking cessation on field carcinogenesis were assessed.

Findings: Among 331 enrolled patients, the median follow-up was 120 months (range: 1.3-176.9). The cumulative incidences of mESCC were 10.4%, 27.2%, and 61.8% in grades A, B, and C, respectively. An increment of 1 unit (22 g ethanol) of alcohol consumption and higher LVL grade independently increased the risk for mESCC. Alcohol or smoking cessation reduced this risk (hazard ratio [HR] 0.52, 95% confidence interval [CI]: 0.31-0.88; HR 0.44, 95% CI: 0.25-0.78, respectively), and combined cessation had the greatest impact (HR 0.21, 95% CI: 0.07-0.65). Complete cessation, rather than partial reduction, was necessary to achieve meaningful risk reduction.

Interpretation: Alcohol and tobacco exposure, and a large number of LVL, are major determinants of mESCC. Complete cessation markedly reduces risk, underscoring the importance of behavioural interventions for secondary prevention of field carcinogenesis after ER.

Funding: National Cancer Center Research and Development Fund 36, Japan.

Keywords: Alcohol; Esophageal squamous cell carcinoma; Field carcinogenesis; Lugol-voiding lesion; Metachronous cancer; Tobacco.