Mendelian randomization analysis for identifying circulating inflammatory cytokines and risk of pancreatic cancers

Inflammation is intricately linked to the emergence and advancement of most cancers, playing a pivotal role in their malignant transformation. Observational evidence revealed the role of cytokines in pancreatic cancer (PC) carcinogenesis. However, observational studies may be limited by small sample sizes, confounding factors, and reverse causality when establishing a correlation between inflammatory cytokines and PC risk.

Conducting a two-sample Mendelian randomization analysis, we investigated the potential relationship between inflammatory cytokines in circulation and pancreatic cancer. Data from the most extensive genome-wide association studies (GWAS) on cytokines were utilized, involving 31 112 individuals of European descent. Additionally, the PC GWAS from the Integrative Epidemiology Unit (IEU) analysis of Finnish Biobank data was included, consisting of 605 PC cases and 218 187 controls of European ancestry.

Around 47 cytokines were systematically screened, which revealed that circulating levels of IL-1ra (OR: 0.63; 95% CIs: 0.46-0.87; P-value: 4.9 × 10-4), IP-10 (OR: 0.33; 95% CIs: 0.18-0.59; P-value: 1.8 × 10-4) and macrophage inflammatory protein (MIP)-1a (OR: 1.37; 95% CIs: 1.08-1.75; P-value: 1 × 10-2) predicted by genetic criteria were prominently linked to an elevated risk of overall PC.

Further evidence indicates that certain inflammatory cytokines play critical roles in PC carcinogenesis and that specific inflammatory cytokines can be targeted to prevent PC. Nevertheless, additional research is necessary to assess the potential of these cytokines in detecting PC at an early stage.