Risk factors associated with neuroendocrine tumors: A U.S.-based case-control study

Carcinoids are rare neuroendocrine tumors (NETs); however, their incidence has significantly increased in the United States over the past 30 years. Little is known about the epidemiology of these cancers and their associated risk factors. We evaluated the independent effects of multiple risk factors associated with NETs arising at 5 disease sites (small intestine, stomach, lung, pancreas and rectum). We conducted a retrospective, hospital-based, case-control study involving 740 patients with histologically confirmed NETs and 924 healthy controls. Information on different risk factors was collected, and unconditional logistic regression analysis was used to determine adjusted odds ratios (AORs) and 95% confidence interval (CI) by the maximum-likelihood method. Smoking and alcohol consumption were not associated with NETs development in either men or women. However, a family history of cancer was a significant risk factor for all NETs. A long-term history of diabetes mellitus was a significant risk factor for gastric NETs (AOR = 5.6; 95% CI, 2.1-14.5), particularly in women (AOR = 8.4; 95% CI, 1.9-38.1). Diabetes modified the risk among women with a positive family history of cancer for the development of gastric NETs (AOR = 52.2; 95% CI, 5.5-491.5). Our results suggest that the risk of NETs may mostly explained by genetic factors. The increased risk of gastric NETs in women with both diabetes and a positive family history of cancer suggest that women may have a greater genetic susceptibility to NETs than men.