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Family History of Cancer and Associated Risk of Developing Neuroendocrine Tumors: A Case-Control Study

Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: James C. Yao, Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-2828; Fax: 713-745-1163. E-mail: jyao{at}mdanderson.org

Background: Carcinoids are rare neuroendocrine tumors (NET). Familial clusterings of NETs are rarely reported, except for a small proportion associated with multiple endocrine neoplasia syndrome type 1. We evaluated the effect of positive family history of NET as well as other cancers on the development of NETs arising at five different locations.

Methods: We conducted a retrospective, hospital-based, case-control study involving 740 patients with histologically confirmed NETs and 924 healthy controls. Information on family history of cancer was collected, and unconditional logistic regression analysis was used to determine adjusted odds ratios (AOR) and 95% confidence intervals (CI).

Results: The authors observed a significant relationship between first-degree relatives with cancers and the development of NETs arising at the small intestine, stomach, lung, and pancreas; AORs (95% CI) were 1.6 (1.1-2.4), 2.5 (1.1-6.3), 2.6 (1.5-4.5), and 1.8 (1.1-3.1), respectively. A first-degree family history of esophageal cancer was significantly associated with pancreatic NETs; AOR, 5.6 (95% CI, 1.1-29.6). There was a 70% and 130% increased risk of developing small intestinal NETs among subjects with family histories of colorectal cancer and prostate cancer, respectively. Moreover, individuals with a family history of lung cancer had a 2-fold increase in risk of developing pulmonary NETs.

Conclusions: Having a first-degree relative with any cancer in general, and NET in particular, was a risk factor for NETs. The elevated risk of developing NETs extended to individuals with a family history of other cancers (not NETs) among first-degree relatives. These results suggested that risk of NETs may be partially explained by genetic factors. (Cancer Epidemiol Biomarkers Prev 2008;17(4):959–65)