title: Evidence for a heritable contribution to neuroendocrine tumors of the small intestine.
abstract: Small intestinal neuroendocrine tumors (SI-NETs) are rare tumors arising from the enterochromaffin cells of the gut. Having a first-degree relative with a SI-NET has been shown to confer a substantial risk arising from shared environment and genetics. Heritable risk was examined using a computerized genealogy linked to historical statewide cancer data. A population-based analysis of the observed familial clustering of SI-NETs was performed to assess the genetic risk in distant relatives. A test for significant excess relatedness of 384 individuals with genealogy data and histologically confirmed SI-NETs was performed by comparing pairwise relatedness of cases to 1000 sets of matched controls. Overall significant excess pairwise relatedness was found for the 384 cases (P<0.001) and was still observed when closer than first cousin relationships were ignored (P=0.041). Relative risks (RRs) for SI-NETs were estimated as a ratio of observed to expected number of SI-NET cases among each relationship class. Siblings have a 13.4-fold (P<0.0001) and parents have a 6.5-fold (P=0.143) RR, suggesting both genetic and environmental influences. The risk extends out to third-degree relatives with a 2.3-fold RR (P=0.008). Metachronous cancers were also reported in 26% of the SI-NET cases demonstrating an increased RR of colon, bladder, non-Hodgkin lymphoma, melanoma, and prostate cancers. Although SI-NETs are rare, relatives of these cases are at a significantly elevated risk of developing a SI-NET due to heritable genetic factors. Definition of the genetic risk factors will be an important tool for earlier diagnosis and better outcomes for SI-NETs.
authors.affiliation: Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA Deb.neklason@hci.utah.edu.
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Neklason
authors.affiliation: Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA.
authors.forename: James
authors.initials: J
authors.lastname: VanDerslice
authors.affiliation: Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.affiliation: Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA Division of Genetic EpidemiologyDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USAHuntsman Cancer InstituteUniversity of Utah, 2000 Circle of Hope, Room 3265, Salt Lake City, Utah 84112-5550, USADivision of Public HealthDepartment of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USAGeorge E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, Utah, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D012307:Risk Factors
keywords: familial; genetics; neuroendocrine tumor; population; relative risk; small intestine