Studies on a longitudinal relationship between smoking status and intestinal metaplasia (IM), a premalignant lesion of stomach cancer, are limited. Here we examined the association of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of endoscopic IM. This cohort study included 199,235 Korean adults free of endoscopic IM who underwent upper endoscopy at baseline and subsequent visits and who were followed for up to 6.8 years (median, 3.7 years). Former and current smoking status and pack-years based on self-reports were associated with an increased risk of new-onset IM in men but not in women. However, urinary cotinine levels were positively associated with incident IM in a dose-response manner in both men and women. For men, the multivariable-adjusted HR [95% confidence interval (CI)] for incident IM comparing the urinary cotinine levels of 50 to 99 ng/mL, 100 to 499 ng/mL, and ≥500 ng/mL with <50 ng/mL were 1.20 (0.94-1.55), 1.26 (1.14-1.40), and 1.54 (1.44-1.64), respectively, whereas for women, corresponding HR (95% CI) were 0.75 (0.19-2.99), 1.86 (1.20-2.88), and 1.57 (1.07-2.30), respectively. These associations were observed when changes in smoking status and other confounders were updated during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, urinary cotinine levels were independently associated with an increased incidence of endoscopic IM in a dose-response manner. Collectively, these data confirm smoking as an independent risk factor for the development of gastric IM, a precursor lesion of stomach cancer. SIGNIFICANCE: A large-scale cohort study of nearly 200,000 adults associates smoking with increased risk for gastric intestinal metaplasia, a precursor lesion of stomach cancer.
©2018 American Association for Cancer Research.