Causal effects of smoking, alcohol consumption, and coffee intake on hepatobiliary and pancreatic diseases: A Mendelian randomization study

Background: Hepatobiliary and pancreatic diseases, such as cirrhosis, hepatocellular carcinoma, cholelithiasis, and pancreatitis, are major global health challenges. Lifestyle factors like smoking, alcohol consumption, and coffee intake are commonly studied for their health impacts. However, observational studies often face issues with confounding factors and reverse causality, making it difficult to establish causal relationships. Methods: This research uses Mendelian randomization (MR) to investigate the causal effects of smoking, alcohol use, and coffee intake on 10 hepatobiliary and pancreatic diseases. Genetic data from the Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) and self-reported GWAS were used to derive instrumental variables (IVs). The outcomes were obtained from the FinnGen and UK Biobank cohorts. Univariable and multivariable MR analyses were conducted to assess the associations. Results: Genetic predisposition to tobacco use was associated with increased risks of acute pancreatitis, alcoholic hepatitis, chronic pancreatitis, cirrhosis, gallstones, liver cancer, and pancreatic cancer. Alcohol consumption was linked to acute pancreatitis, chronic pancreatitis, alcoholic liver disease, hepatic cancer, and cholangitis. Coffee intake showed minimal associations, with a slight protective effect against non-alcoholic steatohepatitis. Conclusions: This study confirms the harmful effects of inhaling tobacco and consuming alcohol on hepatobiliary and pancreatic diseases. It highlights the need for public health strategies to reduce tobacco use and heavy alcohol consumption. Coffee intake showed minimal effects, suggesting further research is needed to understand its relationship with hepatobiliary health.