Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Diabetes Investig. 2020 May;11(3):585-593. doi: 10.1111/jdi.13166. Epub 2019 Nov 28.
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.
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.
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).
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.
目的/引言：在大多数观察性研究中，糖尿病患者的血清肿瘤相关抗原 19-9（CA19-9）水平升高；然而，CA19-9 与糖尿病之间是否存在因果关系尚不清楚。
我们的研究基于包含 27009 人的东风-同济队列进行。我们首先在一项前瞻性队列研究（12700 人）中研究了血清 CA19-9 水平与新发糖尿病风险之间的关联。然后，我们使用孟德尔随机化分析在横断面研究（3349 例糖尿病患者和 8341 例对照）中探讨 CA19-9 与糖尿病风险之间的潜在因果关系。通过在先前的血清 CA19-9 水平全基因组关联研究中鉴定的五个单核苷酸多态性（FUT6 中的 rs17271883、rs3760776 和 rs3760775、CA11 中的 rs11880333、B3GNT3 中的 rs265548 和 FUT2 中的 rs1047781），计算 CA19-9 增加的等位基因的加权遗传风险评分。
在前瞻性研究中，在平均 4.54 年的随访期间，共诊断出 1004 例新发糖尿病患者。在调整混杂因素后，升高的血清 CA19-9 水平与更高的新发糖尿病风险相关，每标准偏差（12.17 U/mL）CA19-9 增加的风险比为 1.20（95%置信区间 1.11-1.30）。使用遗传评分估计未混杂的影响，我们没有发现 CA19-9 与糖尿病风险之间存在因果关系（每增加一个加权 CA19-9 增加的等位基因的比值比：0.99，95%置信区间 0.94-1.04；P=0.61）。
本研究不支持血清 CA19-9 与糖尿病风险之间的因果关系。CA19-9 可能是新发糖尿病风险的潜在生物标志物。
