Diabetes, Smoking, Alcohol Use, and Family History of Cancer as Risk Factors for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

Abstract

Background and Aims: Risk factors for pancreatic neuroendocrine tumors (PNETs) are not well understood. The aim of this systematic review was to assess if diabetes mellitus, smoking, alcohol use, and family history of cancer are risk factors for PNETs. Methods: MEDLINE and abstracts from the European and North American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for studies published until October 2013. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Five studies evaluating 4 individual populations were included (study accrual period 2000-2011) into the meta-analysis, involving 827 cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All studies had a case-control design and described regional series. The pooled adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p < 0.01; I² = 60.4%) for history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I² = 45.8%) for ever smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I² = 0.0%) for heavy smoking, 1.09 (95% CI: 0.64-1.85; p = 0.75; I² = 85.2%) for ever alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I² = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p < 0.01; I² = 0.0%) for first-degree family history of cancer. Conclusions: Diabetes mellitus and first-degree family history of cancer are associated with an increased risk of sporadic PNET. There was also a trend for diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a risk factor for PNET, but there was considerable heterogeneity in the meta-analysis. These results suggest the need for a larger, homogeneous, international study for the clarification of risk factors for the occurrence of PNET.

Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study

“…With respect to the association between diabetes and PNETs risk, several studies141517 including two meta-analyses1225 have consistently indicated diabetes as a potential risk factor for development of PNETs. Hassan et al .…”

“…Many epidemiological studies have evaluated risk factors for pancreatic adenocarcinomas91011; however, little is known about the possible role of environmental risk factors for sporadic PNETs12. Several potential risk factors have been postulated for PNETs, which include social economic factors, family history of cancer (FHC), smoking habits, alcohol consumption, body mass index (BMI) and type 2 diabetes1314151617.…”

Pancreatic Exocrine Insufficiency in Pancreatic Cancer

“…Nevertheless, it is noteworthy that the malabsorption of fat generally does not occur until pancreatic lipase and trypsin levels fall to below 5%–10% of normal production. Table 1 summarizes the different mechanisms underlying intraluminal pancreatic enzyme deficiency (Table 1) [7,8,9,10]. …”

“…Ductal adenocarcinoma and its variants make up more than 90% of all malignant exocrine pancreatic tumors, while pancreatic endocrine tumors display a low incidence (1%) but a considerable prevalence (around 10% of all pancreatic masses) [9]. Rarer tumors include cell acinar carcinomas, sarcomas, and tumors of uncertain histogenesis, which account for a minority of cases [10].…”

Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors

“…PNETs have been poorly studied, due to their rarity, and compared to other cancer types very little is known regarding either environmental or genetic risk factors for their occurrence. The role of traditional cancer risk factors such as smoking and alcohol consumption seems controversial678. On the contrary, type two diabetes (T2D) and family history of cancer have been consistently associated with PNET risk78.…”