目的:散发性GEP-NEN的危险因素仍未明确。确定主要临床风险因素代表了这项研究的目的,该研究由三个意大利NENs转诊中心进行。
方法:我们进行了一项回顾性病例对照研究,包括148个连续散发性GEP-NENs和210个年龄和性别匹配的对照。我们收集了临床特征的数据,癌症家族史和其他潜在危险因素。
结果:平均年龄为58.3±15.8岁;50%的男性,原发部位为胰腺(50.7%),其次是回肠(22.3%)。62.8%和29.1%的病例分别为G1和G2;40%的病例在诊断时患有局部晚期或转移性疾病。GEP-NENs的独立危险因素是:非神经内分泌GEP癌家族史(OR2.16,95%CI1.31-3.55,p=0.003),2型糖尿病(T2DM)(OR2.5,95%CI1.39-4.51,p=0.002)和肥胖(OR1.88,95%CI1.18-2.99,p=0.007)。在T2DM受试者中,二甲双胍的使用是一个保护因素(OR0.28,95%CI0.08-0.93,p=0.049)。T2DM还与更晚期(OR2.39,95%CI1.05-5.46,p=0.035)和进行性疾病(OR2.47,95%CI1.08-5.34,p=0.03)相关。按主要地点对案件进行分层,胰腺NENs的独立危险因素是T2DM(OR2.57,95%CI1.28-5.15,p=0.008)和肥胖(OR1.98,95%CI1.11-3.52,p=0.020),而对于非神经内分泌GEP癌(OR2.46,95%CI1.38-4.38,p=0.003)和肥胖(OR1.90,95%CI1.08-3.33,p=0.026)的肠道NENs家族史。
结论:这项研究加强了非神经内分泌GEP癌家族史的作用,T2DM和肥胖是GEP-NENs的独立危险因素,提示二甲双胍作为T2DM受试者的保护因素。如果确认,这些发现可能对GEP-NENs的预防策略产生重大影响.
OBJECTIVE: Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs.
METHODS: We performed a retrospective
case-control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors.
RESULTS: Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31-3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39-4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18-2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08-0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05-5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08-5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28-5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11-3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38-4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08-3.33, p = 0.026).
CONCLUSIONS: This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.