The effects of genetically determined plasma methyltransferases on digestive system cancers: a comprehensive...

The causal relationship between plasma methyltransferase protein concentrations and the onset of digestive system cancers remains unclear. This study employed a Mendelian randomization (MR) analysis to explore potential causal relationships.

A bidirectional two-sample MR analysis was conducted to systematically investigate causal associations. Data from the FinnGen Biobank and the European Bioinformatics Institute (EBI) were used for verification. This analysis focused on 14 types of methyltransferases and 5 types of digestive system cancers.

The analysis identified specific methyltransferases associated with increased risks for certain digestive system malignancies. Notably, dual verification confirmed that HEMK2 is associated with an increased risk of colorectal cancer [Odds Ratio (OR) = 1.28; 95% CI: 1.06-1.55 for FinnGen; OR = 1.18; 95% CI: 1.07-1.29 for EBI] and liver cancer (OR = 2.31; 95% CI: 1.29-4.14 for FinnGen; OR = 1.38; 95% CI: 1.08-1.76 for EBI). NTMT1 was also associated with colorectal cancer (OR = 1.16; 95% CI: 1.03-1.30 for FinnGen; OR = 1.10; 95% CI: 1.04-1.17 for EBI) and liver cancer (OR = 1.59; 95% CI: 1.11-2.27 for FinnGen; OR = 1.21;95%CI: 1.04-1.40 for EBI). We also found that some methyltransferases exhibit either harmful or protective effects in digestive system cancers; however, these findings have not been validated by another independent database. Therefore, the interpretation of these results requires caution.

This study reveals that certain methyltransferases are associated with an increased risk of some digestive system cancers. HEMK2 and NTMT1 emerged as candidate genetically predicted biomarkers, meriting further research to elucidate their mechanistic functions and potential clinical applicability. Furthermore, as all genetic information in this study originates from European cohorts, the conclusions are primarily relevant to this population and necessitate validation in diverse ethnic groups.