Luo Fada, Mou Weicheng, Zeng Yong, Ouyang Xingwei, Bold Richard J, Krishna Somashekar G, Yamaguchi Atsushi, Zhang Li
Department of Medical School, Kunming University of Science and Technology, Kunming, China.
Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
J Gastrointest Oncol. 2025 Jun 30;16(3):1233-1247. doi: 10.21037/jgo-2025-305. Epub 2025 Jun 27.
Despite extensive observational evidence implicating lifestyle habits, metabolic factors, hormone levels, predisposing genetic conditions, medications, and other exposures, causal inference regarding pancreatic ductal adenocarcinoma (PDAC) risk factors remain contentious due to residual confounding. This Mendelian randomization (MR) meta-analysis was employed to address unresolved etiological controversies and systematically investigate causal relationships between these modifiable factors and clinical outcomes.
We conducted a systematic assessment and meta-analysis focusing on studies that employed MR methods to assess the correlation between impact factors and PDAC. We searched five databases, including PubMed, Embase, Web of Science, Scopus, and Ovid, and ultimately included 82 studies, with 292 independent findings. A meta-analysis was performed on 56 of these influencing factors.
Our study found that several factors may be risk factors for PDAC, including body mass index (BMI) [odds ratio (OR): 1.23, 95% confidence interval (CI): 1.10-1.36], gut microbiota (OR: 1.25, 95% CI: 1.05-1.49), diabetes mellitus (OR: 1.07, 95% CI: 1.02-1.13), body size (OR: 1.72, 95% CI: 1.48-2.00), fasting insulin (OR: 2.23, 95% CI: 1.61-3.09), hip circumference (OR: 1.34, 95% CI: 1.11-1.61) and inflammatory bowel disease (IBD) (OR: 1.18, 95% CI: 1.04-1.34). Conversely, potential protective factors against PDAC included lycopene intake (OR: 0.87, 95% CI: 0.77-0.99) and cathepsin E levels (OR: 0.96, 95% CI: 0.94-0.99), and these factors should be further investigated.
This meta-analysis of MR studies identified several risk and protective factors for pancreatic cancer, with most showing low heterogeneity. However, these findings represent associations, not causality. These findings may inform clinical risk assessment while awaiting further validation. The study highlights the need for continued research focusing on diverse populations, mechanistic studies, longitudinal investigations, and translational work to advance understanding and develop effective strategies for pancreatic cancer prevention and treatment.
尽管有大量观察性证据表明生活方式习惯、代谢因素、激素水平、遗传易感性疾病、药物及其他暴露因素与胰腺癌有关，但由于残留混杂因素，关于胰腺导管腺癌（PDAC）危险因素的因果推断仍存在争议。本孟德尔随机化（MR）荟萃分析旨在解决未解决的病因学争议，并系统研究这些可改变因素与临床结局之间的因果关系。
我们进行了一项系统评估和荟萃分析，重点关注采用MR方法评估影响因素与PDAC之间相关性的研究。我们检索了五个数据库，包括PubMed、Embase、Web of Science、Scopus和Ovid，最终纳入82项研究，有292个独立研究结果。对其中56个影响因素进行了荟萃分析。
我们的研究发现，几个因素可能是PDAC的危险因素，包括体重指数（BMI）[比值比（OR）：1.23，95%置信区间（CI）：1.10 - 1.36]、肠道微生物群（OR：1.25，95%CI：1.05 - 1.49）、糖尿病（OR：1.07，95%CI：1.02 - 1.13）、体型（OR：1.72，95%CI：1.48 - 2.00）、空腹胰岛素（OR：2.23，95%CI：1.61 - 3.09）、臀围（OR：1.34，95%CI：1.11 - 1.61）和炎症性肠病（IBD）（OR：1.18，95%CI：1.04 - 1.34）。相反，PDAC的潜在保护因素包括番茄红素摄入量（OR：0.87，95%CI：0.77 - 0.99）和组织蛋白酶E水平（OR：0.96，95%CI：0.94 - 0.99），这些因素应进一步研究。
这项MR研究的荟萃分析确定了几个胰腺癌的风险和保护因素，大多数显示低异质性。然而，这些发现仅代表关联，而非因果关系。这些发现可为临床风险评估提供参考，同时等待进一步验证。该研究强调需要继续开展针对不同人群的研究、机制研究、纵向调查和转化研究，以增进理解并制定有效的胰腺癌预防和治疗策略。
