Complex interplay between type 2 diabetes mellitus and pancreatic cancer: insights from observational and mendelian randomization analyses.

IF 3.4 2区 医学 Q2 ONCOLOGY
Yuxin Wang, Lu Xie, Ye Gu, Hangbin Jin, Jianfeng Yang, Qiang Liu, Xiaofeng Zhang
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引用次数: 0

Abstract

Background: To investigate the causal relationship between type 2 diabetes mellitus (T2DM), pancreatic cancer (PC) risk and identify the mediating effects of various risk factors on that relationship.

Methods: 581 PC patients and 582 healthy controls who visited our center from January 2013 to December 2023 were included in this retrospective study. Multivariable logistic regression was performed to evaluate the association between T2DM and PC through odds ratios (ORs) and 95% confidence intervals (CIs). Mendelian randomization (MR) studies were then conducted to explore the causal relationship between T2DM and PC, and causal mediation analysis (CMA) to examine the mediating role of common risk factors.

Results: After adjusting for confounding factors, retrospective analysis revealed significant association between new-onset diabetes mellitus (NODM) and PC risk, with insulin treatment also linked to increased PC development. The standard inverse-variance weighted (IVW) method indicated that genetic susceptibility to T2DM was associated with an increased risk of developing PC (OR = 1.11; 95% CI = 1.034-1.193). Furthermore, MR showed T2DM, insulin treatment, FGF-4, and sulfhydryl oxidase 2 may be independently associated with the prevalence of PC. Specially, CMA demonstrated that insulin treatment, FGF4, and sulfhydryl oxidase 2 mediate the pathway from T2DM to PC, contributing 56.8%, 55.8%, and 5.9% of the total effect, respectively.

Conclusion: This study supports the association between T2DM, specifically NODM, and increased PC risk, with insulin therapy, FGF4, and sulfhydryl oxidase 2 mediating this pathway. Further research is required to elucidate the mechanisms underlying these mediating effects.

Clinical trial number: not applicable.

2型糖尿病和胰腺癌之间复杂的相互作用:来自观察性和孟德尔随机分析的见解。
背景:探讨2型糖尿病(T2DM)与胰腺癌(PC)风险之间的因果关系,并确定各种危险因素在两者关系中的中介作用。方法:选取2013年1月至2023年12月在我中心就诊的581例PC患者和582例健康对照者进行回顾性研究。通过比值比(or)和95%置信区间(ci),采用多变量logistic回归来评估T2DM和PC之间的关系。然后通过孟德尔随机化(MR)研究来探索T2DM和PC之间的因果关系,并通过因果中介分析(CMA)来检验常见危险因素的中介作用。结果:在调整混杂因素后,回顾性分析显示新发糖尿病(NODM)与PC风险之间存在显著关联,胰岛素治疗也与PC发展增加有关。标准反方差加权(IVW)方法显示,T2DM遗传易感性与PC发病风险增加相关(OR = 1.11;95% ci = 1.034-1.193)。此外,磁共振显示T2DM、胰岛素治疗、FGF-4和巯基氧化酶2可能与PC患病率独立相关。特别地,CMA表明胰岛素治疗、FGF4和巯基氧化酶2介导T2DM到PC的通路,分别占总效应的56.8%、55.8%和5.9%。结论:本研究支持T2DM(特别是NODM)和PC风险增加与胰岛素治疗、FGF4和巯基氧化酶2介导这一途径有关。需要进一步的研究来阐明这些中介作用的机制。临床试验号:不适用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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