Abstract
<title>Abstract</title> <p> Background <italic>Helicobacter pylori</italic> -uninfected gastric cancers are rare and predominantly undifferentiated. We investigated clinical factors associated with <italic>H. pylori</italic> -uninfected undifferentiated-type early gastric cancer (HPUGC). Methods This single-center retrospective matched analysis included 132 patients who underwent endoscopic submucosal dissection for HPUGC between December 2007 and December 2021 and 5788 <italic>H. pylori</italic> -uninfected individuals without gastric cancer who underwent screening endoscopy in 2021. Propensity score matching was performed for age and sex. Results After matching, 131 participants were included in each group. Smoking history, current smoking, and median Brinkman index were higher in the HPUGC group than in controls (70.2% vs. 42.0%, 42.0% vs. 13.0%, and 340 vs. 0, respectively; all P < 0.001). Receiver operating characteristic analysis identified a Brinkman index of 170 as an exploratory cutoff. A Brinkman index ≥ 170 was independently associated with HPUGC in multivariable analysis (odds ratio, 5.06; 95% confidence interval, 2.89–8.87). Conclusions Smoking exposure was associated with HPUGC. The exploratory cutoff requires validation. Further studies should determine whether smoking exposure can contribute to risk stratification in <italic>H. pylori</italic> -uninfected individuals. </p>