胰腺导管腺癌危险因素在导管内乳头状黏液性肿瘤进展中的作用。
Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression.
作者信息
Gentiluomo Manuel, Corradi Chiara, Arcidiacono Paolo Giorgio, Crippa Stefano, Falconi Massimo, Belfiori Giulio, Farinella Riccardo, Apadula Laura, Lauri Gaetano, Bina Niccolò, Rizzato Cosmeri, Canzian Federico, Morelli Luca, Capurso Gabriele, Campa Daniele
机构信息
Department of Biology, University of Pisa, Pisa, Italy.
Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
出版信息
Front Oncol. 2023 Jun 6;13:1172606. doi: 10.3389/fonc.2023.1172606. eCollection 2023.
INTRODUCTION
Pancreatic ductal adenocarcinoma (PDAC) is lethal due to its late diagnosis and lack of successful treatments. A possible strategy to reduce its death burden is prevention. Intraductal papillary mucinous neoplasms (IPMNs) are precursors of PDAC. It is difficult to estimate the incidence of IPMNs because they are asymptomatic. Two recent studies reported pancreatic cysts in 3% and 13% of scanned subjects. The possibility of identifying a subgroup of IPMN patients with a higher probability of progression into cancer could be instrumental in increasing the survival rate. In this study, genetic and non-genetic PDAC risk factors were tested in a group of IPMN patients under surveillance.
METHODS
A retrospective study was conducted on 354 IPMN patients enrolled in two Italian centres with an average follow-up of 64 months. With the use of DNA extracted from blood, collected at IPMN diagnosis, all patients were genotyped for 30 known PDAC risk loci. The polymorphisms were analysed individually and grouped in an unweighted polygenic score (PGS) in relation to IPMN progression. The ABO blood group and non-genetic PDAC risk factors were also analysed. IPMN progression was defined based on the development of worrisome features and/or high-risk stigmata during follow-up.
RESULTS
Two genetic variants (rs1517037 and rs10094872) showed suggestive associations with an increment of IPMN progression. After correction for multiple testing, using the Bonferroni correction, none of the variants showed a statistically significant association. However, associations were observed for the non-genetic variables, such as smoking status, comparing heavy smokers with light smokers (HR = 3.81, 95% 1.43-10.09, = 0.007), and obesity (HR = 2.46, 95% CI 1.22-4.95, = 0.012).
CONCLUSION
In conclusion, this study is the first attempt to investigate the presence of shared genetic background between PDAC risk and IPMN progression; however, the results suggest that the 30 established PDAC susceptibility polymorphisms are not associated with clinical IPMN progression in a sample of 354 patients. However, we observed indications of cigarette smoking and body mass index (BMI) involvement in IPMN progression. The biological mechanism that could link these two risk factors to progression could be chronic inflammation, of which both smoking and obesity are strong promoters.
引言
胰腺导管腺癌（PDAC）因其诊断较晚且缺乏有效的治疗方法而具有致命性。降低其死亡负担的一种可能策略是预防。导管内乳头状黏液性肿瘤（IPMNs）是PDAC的癌前病变。由于IPMNs无症状，因此很难估计其发病率。最近的两项研究报告称，在接受扫描的受试者中，胰腺囊肿的发生率分别为3%和13%。识别出一组进展为癌症可能性更高的IPMN患者，这对于提高生存率可能具有重要意义。在本研究中，对一组接受监测的IPMN患者进行了遗传和非遗传PDAC风险因素检测。
方法
对在意大利两个中心登记的354例IPMN患者进行回顾性研究，平均随访64个月。利用在IPMN诊断时采集的血液中提取的DNA，对所有患者进行30个已知PDAC风险位点的基因分型。对多态性进行单独分析，并根据IPMN进展情况将其分组为未加权多基因评分（PGS）。还分析了ABO血型和非遗传PDAC风险因素。IPMN进展是根据随访期间出现令人担忧的特征和/或高风险特征来定义的。
结果
两个基因变异（rs1517037和rs10094872）显示出与IPMN进展增加存在提示性关联。在使用Bonferroni校正进行多重检验校正后，没有一个变异显示出统计学上的显著关联。然而，在非遗传变量方面观察到了关联，例如吸烟状况，重度吸烟者与轻度吸烟者相比（HR = 3.81，95% 1.43 - 10.09，P = 0.007），以及肥胖（HR = 2.46，95% CI 1.22 - 4.95，P = 0.012）。
结论
总之，本研究首次尝试探究PDAC风险与IPMN进展之间是否存在共同的遗传背景；然而，结果表明，在354例患者的样本中，30个已确定的PDAC易感性多态性与临床IPMN进展无关。然而，我们观察到吸烟和体重指数（BMI）与IPMN进展有关。将这两个风险因素与进展联系起来的生物学机制可能是慢性炎症，吸烟和肥胖都是慢性炎症的强烈促进因素。
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