title: Diabetes, smoking, alcohol use, and family history of cancer as risk factors for pancreatic neuroendocrine tumors: a systematic review and meta-analysis.
abstract: OBJECTIVE
  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; I(2) = 60.4%) for history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I(2) = 45.8%) for ever smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I(2) = 0.0%) for heavy smoking, 1.09 (95% CI: 0.64-1.85; p = 0.75; I(2) = 85.2%) for ever alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I(2) = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p < 0.01; I(2) = 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.
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway.
authors.forename: Sven-Petter
authors.initials: SP
authors.lastname: Haugvik
authors.forename: Per
authors.initials: P
authors.lastname: Hedenström
authors.forename: Emilie
authors.initials: E
authors.lastname: Korsæth
authors.forename: Roberto
authors.initials: R
authors.lastname: Valente
authors.forename: Alastair
authors.initials: A
authors.lastname: Hayes
authors.forename: Darko
authors.initials: D
authors.lastname: Siuka
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Ivar Prydz
authors.initials: IP
authors.lastname: Gladhaug
authors.forename: Björn
authors.initials: B
authors.lastname: Lindkvist
authors.forename: Gabriele
authors.initials: G
authors.lastname: Capurso
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D006801:Humans; D018358:Neuroendocrine Tumors / Q000453:epidemiology*; D009656:North America / Q000453:epidemiology; D010190:Pancreatic Neoplasms / Q000453:epidemiology*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*