Simple SummaryIt is thought that allergic diseases could hamper or trigger carcinogenesis by enhancing host immune defenses or persisting inflammation, respectively. The gastrointestinal (GI) tract plays a crucial role in building the immune system via the gut barrier and through communicating with the microbiome. We hypothesized that allergic diseases may be linked with the occurrence of GI tract cancers. Analyzing national health check-up data, we found that, overall, allergic diseases which consist of allergic rhinitis, asthma, and atopic dermatitis reduced the risk of malignancy in the esophagus, stomach, colorectum, and liver. Given that gastric and liver cancers are typical infection-related malignancies, the inverse associations between allergic diseases and the subsequent development of GI cancers in the present study supports the cancer immunosurveillance hypothesis. This result could provide a clue for the novel approach to the prevention and treatment of GI cancers.AbstractThe aim of this study was to investigate the effect of allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, on the development of gastrointestinal (GI) cancers. We analyzed 9,892,633 Korean adults who underwent a medical check-up in the year 2009, and they were followed up until the year 2017. Allergic diseases and cancers were defined using the International Classification of Disease Codes. A Cox proportional hazards model was adapted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). During a 7.3-year follow-up period, 48,045 patients were diagnosed with cancer. For all-combined allergic diseases, significant inverse associations were observed for cancers of the esophagus, stomach, colorectum, and liver (adjusted hazard ratios (aHRs [95% confidence interval, CI] 0.86 [0.82–0.91], 0.93 [0.91–0.94], 0.95 [0.93–0.96], and 0.90 [0.88–0.92], respectively). The sex-stratified analysis showed that the preventive effect of allergic diseases was persistent in gastric, colorectal, and liver cancers regardless of sex, while the inverse associations with esophageal and pancreatic cancers were observed only in men (aHR [95% CI] 0.84 [0.80–0.89] and 0.96 [0.93–0.99]). Allergic diseases, particularly allergic rhinitis, in adults were significantly associated with a decreased risk of most GI cancers, except for gallbladder and biliary tract cancers.