Oral leukoplakia and the long‐term risk of upper gastrointestinal cancer deaths in the Linxian dysplasia population

BACKGROUND: To investigate oral leukoplakia (OL) and risk of upper gastrointestinal (UGI) cancer deaths in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. METHODS: A total of 3318 subjects with esophageal squamous dysplasia enrolled on 1 May 1985, and were followed up until 30 September 2015. Participants with OL at baseline were treated as an exposed group, while the remainder was selected as a control group. All subjects were followed monthly and reviewed quarterly by the Linxian Cancer Registry. Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During the 30‐year follow‐up, a total of 902 UGI cancer deaths occurred, including 541 esophageal squamous cell carcinoma (ESCC) related, 284 gastric cardia carcinoma (GCC) related, and 77 gastric noncardia carcinoma (GNCC) related deaths. Relative to subjects without OL, the long‐term risk of ESCC mortality in participants with OL increased by 26.1% (HR = 1.26, 95% CI: 1.05–1.52). In the subgroup analyses, adverse effects of OL on ESCC mortality were observed especially in younger subjects (HR = 1.48, 95% CI: 1.11–1.97), females (HR = 1.44, 95% CI: 1.11–1.89), non‐smokers (HR = 1.44, 95% CI: 1.15–1.81), nondrinkers (HR = 1.28, 95% CI: 1.04–1.57), and individuals with a family history of cancer (HR = 1.37, 95% CI: 1.05–1.79). No associations were observed between OL and risk of GCC and GNCC mortality. CONCLUSIONS: OL may increase the long‐term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non‐smokers, and subjects with a family cancer history. Future studies are needed to explore the potentially etiological mechanism.