The association between non‐alcoholic fatty liver disease (with or without metabolic syndrome) and extrahepatic cancer development

Abstract Background and Aim This study was designed to determine whether non‑alcoholic fatty liver disease (NAFLD), with or without metabolic syndrome (MetS), is a risk factor for cancer development. Methods We conducted a retrospective longitudinal study at the Center for Preventive Medicine, St. Luke's International Hospital. Among all participants who underwent a health checkup between 2005 and 2019, cancer development tendencies were compared between those who were diagnosed with NAFLD and those who were not. Further evaluation was conducted among NAFLD‐diagnosed participants with versus without MetS in the same manner. Those with a history of a specific liver disease, any type of cancer, or alcohol consumption in any amount at the time of the initial visit were excluded from the study. Results Data were collected from 30 172 participants who underwent health checkups, among whom 4394 (14.6%) had NAFLD. Over the 14‐year follow‐up period, 2086 participants (6.9%) developed cancer. Participants with NAFLD had a higher incidence of digestive organ neoplasms (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.07–1.67), especially in the stomach (OR: 1.40, 95% CI: 1.02–1.94) and small intestine (OR: 2.80, 95% CI: 0.87–8.96), than did those without NAFLD. Participants with NAFLD and MetS had significantly lower rates of neoplasms in respiratory and intrathoracic organs (OR: 0.35 95% CI: 0.14–0.88) and male genital organs (OR: 0.46 95% CI: 0.24–0.87) than did individuals without NAFLD. Conclusions Non‐alcoholic fatty liver disease is associated with the development of gastrointestinal malignancies, while MetS is a negative risk factor for lung and prostate cancer.