Smoking, alcohol and family history of cancer as risk factors for small intestinal neuroendocrine tumors: a systematic review and meta-analysis.

OBJECTIVES: Risk factors for small intestinal neuroendocrine tumors (SI-NETs) are not well understood. The aim of this systematic literature review was to identify risk factors for SI-NET and to further assess these by meta-analysis.

MATERIAL AND METHODS: PubMed and abstracts from the ENETS and NANETS were searched for studies published until May 2015. Eligible studies were selected according to the PRISMA statement.

RESULTS: Seven studies evaluating six individual populations were included (study accrual period 1980-2012) in the meta-analysis, involving 765 (range 17-325) cases and 502,282 (range 52-498,376) controls. All studies were case-control by design. The following risk factors were reported in ≥2 studies: family history of any cancer, family history of colorectal cancer, ever alcohol use and ever smoking. The pooled OR was 1.34 (95% CI: 1.12-1.60; p < .01; I2  = 0.0%) for family history of any cancer, 1.43 (95% CI: 1.15-1.79; p < .01; I2  = 0.0%) for family history of colorectal cancer, 1.04 (95% CI: 0.63-1.72; p = .87; I2  = 65.0%) for ever alcohol use and 1.40 (95% CI: 1.06-1.86; p < .05; I2  = 49.3%) for ever smoking.

CONCLUSIONS: Family history of any cancer, family history of colorectal cancer and history of ever smoking were associated with an increased risk of SI-NET by meta-analysis. Alcohol consumption was not a significant risk factor for SI-NET. However, the studies reporting smoking and alcohol had a high degree of heterogeneity. Therefore, further studies are needed for clarification of smoking and alcohol as risk factors for the occurrence of SI-NET.