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

• Main Authors: Zhaoyang Li, Jing Wang, Xu Han, Fei Wang, Hua Hu, Jing Yuan, Ping Yao, Sheng Wei, Huan Guo, Dan Zheng, Yuhan Tang, Handong Yang, Meian He
• Format: Article
• Language: English
• Published: Wiley 2020-05-01
• Series: Journal of Diabetes Investigation
• Subjects: Cancer antigen 19‐9; Diabetes mellitus; Mendelian randomization
• Online Access: https://doi.org/10.1111/jdi.13166
• ISSN: 2040-1116; 2040-1124

Abstract 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.