Routine blood and urine biochemical biomarkers in relation to pancreatic cancer risk: a Mendelian randomization analysis

Abstract:

Background and Aims Early detection of pancreatic cancer (PC) remains challenging, and conventional biomarkers such as CA19-9 are inadequate for population screening. Routine blood and urine biochemical markers are widely accessible and reflect systemic physiological status; however, their causal relationships with PC risk remain unclear. Therefore, this study aimed to systematically evaluate the potential causal associations between 35 routine biochemical biomarkers and pancreatic cancer risk using a two-sample Mendelian randomization (MR) framework.Methods A two-sample MR study was conducted using genome-wide association study (GWAS) summary data from the UK Biobank for 35 biochemical traits. Outcome data for PC were obtained from the FinnGen consortium (release R12). The inverse-variance weighted (IVW) method was used as the primary analysis, complemented by MR-Egger, weighted median, and weighted mode approaches. Sensitivity analyses were performed to assess robustness.Results Two kidney function-related traits showed consistent causal associations with PC risk. Genetically predicted higher serum creatinine levels were associated with an 18% increased risk of PC per 1-standard deviation increment (OR=1.18, 95% CI=1.03-1.36, P=0.019), whereas higher estimated glomerular filtration rate (eGFR) was associated with a 17% reduced risk (OR=0.83, 95% CI=0.72-0.97, P=0.016). Sensitivity analyses supported the robustness of these findings, with no evidence of substantial heterogeneity or horizontal pleiotropy.Conclusions This MR study provides genetic evidence supporting a potential causal role of kidney function-related pathways in pancreatic cancer. Serum creatinine and eGFR may serve as promising host-related biomarkers for risk stratification and early detection, warranting further mechanistic and prospective validation.