Valente Roberto, Hayes Alastair J, Haugvik Sven-Petter, Hedenström Per, Siuka Darko, Korsæth Emilie, Kämmerer Daniel, Robinson Stuart M, Maisonneuve Patrick, Delle Fave Gianfranco, Lindkvist Bjorn, Capurso Gabriele
Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy.
Department of General SurgeryRoyal Infirmary of Edinburgh, Edinburgh, UK.
Endocr Relat Cancer. 2017 Aug;24(8):405-414. doi: 10.1530/ERC-17-0040. Epub 2017 May 31.
Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case-control study was conducted to examine the association of selected environmental, family and medical exposure factors using a standardized questionnaire in face-to-face interviews. A ratio of 1:3 cases to controls were sex and age matched at each study site. Adjusted univariate and multivariate logistic regression analysis were performed for statistically significant factors. The following results were obtained: In 201 cases and 603 controls, non-recent onset diabetes (OR 2.09, CI 1.27-3.46) was associated with an increased occurrence of PNENs. The prevalence of non-recent onset diabetes was higher both in cases with metastatic disease (TNM stage III-IV) or advanced grade (G3) at the time of diagnosis. The use of metformin in combination with insulin was also associated with a more aggressive phenotype. Drinking coffee was more frequent in cases with localized disease at diagnosis. Our study concluded that non-recent onset diabetes was associated with an increased occurrence of PNENs and the combination of metformin and insulin was consistent with a more aggressive PNEN phenotype. In contrast to previous studies, smoking, alcohol and first-degree family history of cancer were not associated with PNEN occurrence.
胰腺神经内分泌肿瘤（PNENs）在所有胰腺肿瘤中的患病率为10%。据报道，近几十年来其发病率与胰腺腺癌的发病率同步上升。PNENs相对罕见，在少数发表了潜在危险因素的机构中，研究结果存在异质性。我们的目的是调查来自多个机构的欧洲人群中散发性PNENs发生的潜在风险因素与保护因素之间的关联。开展了一项欧洲多中心病例对照研究，通过标准化问卷进行面对面访谈，以检验选定的环境、家族和医疗暴露因素之间的关联。在每个研究地点，病例与对照的比例为1:3，按性别和年龄匹配。对具有统计学意义的因素进行了单变量和多变量调整逻辑回归分析。结果如下：在201例病例和603例对照中，非近期发病的糖尿病（比值比2.09，可信区间1.27 - 3.46）与PNENs发生率增加相关。在诊断时患有转移性疾病（TNM分期III - IV期）或高级别（G3级）的病例中，非近期发病糖尿病的患病率更高。二甲双胍与胰岛素联合使用也与更具侵袭性的表型相关。在诊断时患有局限性疾病的病例中，喝咖啡更为频繁。我们的研究得出结论，非近期发病的糖尿病与PNENs发生率增加相关，二甲双胍和胰岛素联合使用与更具侵袭性的PNEN表型一致。与既往研究不同，吸烟、饮酒和癌症一级家族史与PNENs的发生无关。
