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Multicenter Study
. 2024 Aug;39(8):1554-1562.
doi: 10.1111/jgh.16570. Epub 2024 Apr 16.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms

Sho Asonuma  1 , Waku Hatta  2 , Tomoyuki Koike  2 , Hideki Okata  1 , Kaname Uno  1 , Wataru Iwai  3 , Masashi Saito  3 , Makoto Yonechi  4 , Daisuke Fukushi  4 , Shoichi Kayaba  5 , Ryosuke Kikuchi  6 , Hirotaka Ito  7 , Jun Fushiya  8 , Ryuhei Maejima  9 , Yasuhiko Abe  10 , Masashi Kawamura  11 , Junya Honda  12 , Yutaka Kondo  13 , Naohiro Dairaku  14 , Shusuke Toda  15 , Kenta Watanabe  16 , Kiichi Takahashi  17 , Hiroharu Echigo  18 , Yasuaki Abe  19 , Hiroyuki Endo  20 , Tomoki Okata  21 , Tatsuya Hoshi  22 , Kenji Kinoshita  23 , Madoka Kisoi  23 , Tomohiro Nakamura  24 , Naoki Nakaya  25 , Katsunori Iijima  16 , Atsushi Masamune  2
Affiliations
Multicenter Study

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms

Sho Asonuma et al. J Gastroenterol Hepatol. 2024 Aug.

Abstract

Background and aim: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk.

Methods: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study.

Results: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001).

Conclusions: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Keywords: ADH1B; ALDH2; Risk stratification; Synchronous gastric cancers.

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