Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, Florida.
Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida.
Cancer Epidemiol Biomarkers Prev. 2023 Sep 1;32(9):1265-1269. doi: 10.1158/1055-9965.EPI-23-0453.
There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer.
Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes.
No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample.
Genetic predisposition to NAFLD is not associated with pancreatic cancer risk.
Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.
非酒精性脂肪性肝病（NAFLD）是否与胰腺癌易感性相关，目前数据存在争议。本研究采用孟德尔随机化（MR）方法，探讨了遗传易患 NAFLD 与胰腺癌风险之间的关系。
利用 PanScan 胰腺癌症队列研究（病例 n=5090，对照 n=8733）和 PanC4 胰腺癌症病例对照研究（病例 n=4163，对照 n=3792）的全基因组关联研究（GWAS）数据，分别采用四种不同的 MR 方法[逆方差加权（IVW）、MR-Egger、简单中位数和惩罚加权中位数]分析 68 种遗传变异与 NAFLD 遗传易感性的关系。然后，我们使用逻辑回归计算比值比（OR）和 95%置信区间（CI），根据肥胖和糖尿病等 PC 危险因素对每个 MR 方法与胰腺癌风险的关系进行评估。
在 PanScan 或 PanC4 样本中，遗传预测的 NAFLD 与胰腺癌风险之间均无关联[例如，PanScan，IVW OR，1.04；95%CI，0.88-1.22；MR-Egger OR，0.89；95%CI，0.65-1.21；PanC4，IVW OR，1.07；95%CI，0.90-1.27；MR-Egger OR，0.93；95%CI，0.67-1.28]。四种 MR 方法均未提示遗传预测的 NAFLD 与胰腺癌风险之间存在关联。
遗传易患 NAFLD 与胰腺癌风险无关。
鉴于 NAFLD 与代谢状况密切相关，NAFLD 与胰腺癌之间的任何关联都可能反映宿主代谢紊乱（如肥胖、糖尿病或代谢综合征），而不一定反映 NAFLD 与胰腺癌之间的因果关系。
