Risk stratification of synchronous gastric cancers including alcohol‐related genetic polymorphisms
Sho Asonuma, Waku Hatta, Tomoyuki Koike, Hideki Okata, Kaname Uno, Wataru Iwai, Masashi Saito, Makoto Yonechi, Daisuke Fukushi, Shoichi Kayaba, Ryosuke Kikuchi, Hirotaka Ito, Jun Fushiya, Ryuhei Maejima, Yasuhiko Abe, Masashi Kawamura, Junya Honda, Yutaka Kondo, Naohiro Dairaku, Shusuke Toda, Kenta Watanabe, Kiichi Takahashi, Hiroharu Echigo, Yasuaki Abe, Hiroyuki Endo, Tomoki Okata, Tatsuya Hoshi, Kenji Kinoshita, Madoka Kisoi, Tomohiro Nakamura, Naoki Nakaya, Katsunori Iijima, Atsushi Masamune- Gastroenterology
- Hepatology
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.