Analyzing the impact of lifestyle and clinical risk factors related to metabolism on the occurrence of digestive system cancers in East Asian populations using a two-sample Mendelian randomization approach

Metabolism-related lifestyle and clinical risk factors play a crucial role in the development of digestive system cancers (DSCs), including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), biliary tract cancer (BTC), and pancreatic cancer (PC). A recent study conducted by researchers delved into the intricate relationship between these risk factors and the onset of DSCs using Mendelian randomization (MR) design.

The study, adhering to the STROBE-MR guidelines, was based on three fundamental assumptions: the relevance assumption, independence assumption, and exclusion restriction assumption. These assumptions formed the basis for designing the MR study, which aimed to explore the associations between 19 predominant metabolism-related lifestyle and clinical risk factors and the development of DSCs. These risk factors were categorized into four groups: lifestyle factors, physical factors, serum parameters, and metabolic comorbidities.

To investigate the potential associations between these risk factors and DSCs, the researchers utilized instrumental variables (IVs) in the MR analysis. IVs for various traits such as lifestyle factors, physical factors, serum parameters, and metabolic comorbidities were collected from different sources focusing on populations of East Asian ancestry. Quality control measures were implemented to ensure the reliability of the instrumental single nucleotide polymorphisms (SNPs) of the risk factors.

GWAS summary statistics of the associations between genetic variants and the development of EC, GC, CRC, HCC, BTC, and PC were retrieved from the Biobank Japan (BBJ), which contains data from approximately 200,000 participants recruited from medical institutions in Japan. The researchers also addressed participant overlap in the MR analysis to avoid inflated type I errors.

Statistical analysis was conducted meticulously, including harmonizing GWAS data, detecting pleiotropic outliers, testing for horizontal pleiotropy, and confirming associations with significant risk factors for cancer. Various MR methods were employed to ensure consistency in the results, and scatter plots were used for visualization. The study applied a Bonferroni-corrected significance level to determine the strength of associations between risk factors and DSCs.

Overall, the study provided valuable insights into the complex interplay between metabolism-related lifestyle and clinical risk factors and the development of DSCs. By utilizing MR design and rigorous statistical analysis, the researchers were able to shed light on the potential impact of these risk factors on the onset of various digestive system cancers. The findings of this study could have significant implications for future research and clinical practice in the field of oncology.