常规血/尿生化指标与胰腺癌风险因果关联的孟德尔随机化分析OA

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.