Association of the presence of allergic disease with subsequent risk of liver cancer in a nationwide retrospective cohort among Koreans

Abstract

A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68–0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62–0.85) but not ICC (aHR, 0.95; 95% CI 0.73–1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62–0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52–0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71–1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71–1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44–0.81) and 0.77 (95% CI 0.64–0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63–0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.

Mendelian Randomization Analyses of Chronic Immune-Mediated Diseases, Circulating Inflammatory Biomarkers, and Cytokines in Relation to Liver Cancer

“…Similar positive associations were observed for type 1 diabetes and systemic lupus erythematosus [44,45]. Kim et al reported a significantly negative association (multivariable-adjusted hazard ratio = 0.80) between asthma and liver cancer [46]. However, using MR analyses, we did not detect a genetic association between these inflammatory diseases and liver cancer.…”

Treatment with Antihistamines and the Risk of Liver Cancer in Patients with Viral Hepatitis: A Multi-Center Cohort Study

“…The strengths of the present study included a large cohort of patients from multiple hospitals and the adjustment of confounders, including age, sex, comorbidities, laboratory data of liver function tests, and comedications. To mitigate potential confounding by indication, diseases with antihistamine indications were incorporated as covariates [ 39 , 40 ]. Furthermore, sensitivity and validation tests were conducted, which yielded consistent results.…”

Atopic dermatitis and risk of 14 site‐specific cancers: A Mendelian randomization study

“…Recent cohort studies conducted in England and Denmark revealed no indication of an association between AD and most cancers, with the exception of lymphoma 8 . However, some studies showed clearly reduced risks for some other types of cancer 9,10 . For instance, a population‐based study in Korea involving a total of 24,089 participants found that AD was significantly associated with a reduced risk of gastric cancer 10 .…”

“…8 However, some studies showed clearly reduced risks for some other types of cancer. 9,10 For instance, a population-based study in Korea involving a total of 24,089 participants found that AD was significantly associated with a reduced risk of gastric cancer. 10 So far, the evidence connecting AD and cancer risk in humans has been based on observational studies, which are susceptible to confounding and reverse causation.…”