Association between cancer antigen 19-9 and diabetes risk: A prospective and Mendelian randomization study

Aims/Introduction Elevated serum cancer antigen 19-9 (CA19-9) levels have been found in diabetes patients in most observational studies; however, whether there is a causal association between CA19-9 and diabetes mellitus is unclear. Materials and Methods Our study was carried out based on the Dongfeng-Tongji cohort comprising 27,009 individuals. We first investigated the associations between serum CA19-9 levels and incident diabetes mellitus risk in a prospective cohort study (12,700 individuals). Then, we explored the potential causal relationship between CA19-9 and diabetes mellitus risk in a cross-sectional study (3,349 diabetes mellitus patients and 8,341 controls) using Mendelian randomization analysis. A weighted genetic risk score was calculated by adding the CA19-9 increasing alleles in five single-nucleotide polymorphisms (rs17271883, rs3760776 and rs3760775 in FUT6, rs11880333 in CA11, rs265548 in B3GNT3, and rs1047781 in FUT2), which were identified in a previous genome-wide association study on serum CA19-9 levels. Results In the prospective study, a total of 1,004 incident diabetes mellitus patients were diagnosed during a mean 4.54-year follow-up period. Elevated serum CA19-9 level was associated with a higher incident diabetes risk after adjustment for confounders, with a hazard ratio of 1.20 (95% confidence interval 1.11-1.30) per standard deviation (12.17 U/mL) CA19-9 increase. Using the genetic score to estimate the unconfounded effect, we did not find a causal association of CA19-9 with diabetes risk (odds ratio per weighted CA19-9-increasing allele: 0.99, 95% confidence interval 0.94-1.04; P = 0.61). Conclusions The present study did not support a causal association of serum CA19-9 with diabetes risk. CA19-9 might be a potential biomarker of incident diabetes mellitus risk.