Peduzzi Giulia, Archibugi Livia, Farinella Riccardo, de Leon Pisani Ruggero Ponz, Vodickova Ludmila, Vodicka Pavel, Kraja Bledar, Sainz Juan, Bars-Cortina David, Daniel Neil, Silvestri Roberto, Uysal-Onganer Pinar, Landi Stefano, Dulińska-Litewka Joanna, Comandatore Annalisa, Campa Daniele, Hughes David J, Rizzato Cosmeri
Department of Biology, University of Pisa, Pisa, Italy.
Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy.
Semin Cancer Biol. 2025 Aug;113:100-129. doi: 10.1016/j.semcancer.2025.05.004. Epub 2025 May 12.
Pancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma (PDAC), is a significant global health issue with high mortality rates. PDAC, though only 3 % of cancer diagnoses, causes 7 % of cancer deaths due to its severity and asymptomatic early stages. Risk factors include lifestyle choices, environmental exposures, and genetic predispositions. Conditions like new-onset type 2 diabetes and chronic pancreatitis also contribute significantly. Modifiable risk factors include smoking, alcohol consumption, non-alcoholic fatty pancreatic disease (NAFPD), and obesity. Smoking and heavy alcohol consumption increase PC risk, while NAFPD and obesity, particularly central adiposity, contribute through chronic inflammation and insulin resistance. Refined sugar and sugar-sweetened beverages (SSBs) are also linked to increased PC risk, especially among younger individuals. Hormonal treatments and medications like statins, aspirin, and metformin have mixed results on PC risk, with some showing protective effects. The gut microbiome influences PC through the gut-pancreas axis, with disruptions leading to inflammation and carcinogenesis. Exposure to toxic substances, including heavy metals and chemicals, is associated with increased PC risk. Glycome changes, such as abnormal glycosylation patterns, are significant in PDAC development and offer potential for early diagnosis. Interactions between environmental and genetic factors are crucial in PDAC susceptibility. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) linked to PDAC, but gene-environment interactions remain largely unexplored. Future research should focus on polygenic risk scores (PRS) and large-scale studies to better understand these interactions and their impact on PDAC risk.
胰腺癌（PC），尤其是胰腺导管腺癌（PDAC），是一个严重的全球健康问题，死亡率很高。PDAC虽然仅占癌症诊断病例的3%，但因其严重性和早期无症状性，却导致了7%的癌症死亡。风险因素包括生活方式选择、环境暴露和遗传易感性。新发2型糖尿病和慢性胰腺炎等病症也有显著影响。可改变的风险因素包括吸烟、饮酒、非酒精性脂肪性胰腺疾病（NAFPD）和肥胖。吸烟和大量饮酒会增加患胰腺癌的风险，而NAFPD和肥胖，尤其是腹型肥胖，则通过慢性炎症和胰岛素抵抗起作用。精制糖和含糖饮料（SSB）也与胰腺癌风险增加有关，尤其是在年轻人中。激素治疗以及他汀类药物、阿司匹林和二甲双胍等药物对胰腺癌风险的影响不一，有些显示出保护作用。肠道微生物群通过肠-胰腺轴影响胰腺癌，其紊乱会导致炎症和致癌作用。接触包括重金属和化学物质在内的有毒物质与胰腺癌风险增加有关。糖组变化，如异常糖基化模式，在PDAC发展中具有重要意义，并为早期诊断提供了潜力。环境和遗传因素之间的相互作用在PDAC易感性中至关重要。全基因组关联研究（GWAS）已经确定了几个与PDAC相关的单核苷酸多态性（SNP），但基因-环境相互作用在很大程度上仍未得到探索。未来的研究应侧重于多基因风险评分（PRS）和大规模研究，以更好地理解这些相互作用及其对PDAC风险的影响。
