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William T. Couldwell and Lisa A. Cannon-Albright


The cause of most pituitary tumors remains unknown, although a genetic contribution is recognized for some. The prevalence of pituitary tumors in the general population is high. Analyzing the Utah Population Database (UPDB), the authors investigated the co-prevalence of other independent primary tumors in patients with known pituitary tumors, both benign and malignant, and in the relatives of these patients.


The authors identified individuals in the Utah Cancer Registry diagnosed with pituitary tumors who also had genealogy data in the UPDB and then calculated relative risks (RRs) of other tumors in these patients and their relatives.


Among the 591 individuals with pituitary tumors, 16 (2.7%) had a malignant pituitary tumor and 77 (13%) had independent primary tumors of other origin. Overall, this is significantly higher than expected (70.6 expected, p = 0.009) within the general population (RR = 1.32, 95% CI 1.06–1.61). A significant excess for several different cancer sites was observed among the first-, second-, and third-degree relatives of the cases, including prostate and other cancers. Independent primary tumors at other sites have markedly elevated co-prevalence in patients harboring pituitary tumors and among their close and distant relatives.


This information will prove useful for counseling patients in whom pituitary tumors have been diagnosed and suggests strong genetic or environmental co-risks for the development of other tumors.

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Diana Abbott, Douglas Brockmeyer, Deborah W. Neklason, Craig Teerlink and Lisa A. Cannon-Albright


A population-based genealogical resource with linked medical data was used to define the observed familial clustering of Chiari malformation Type I (CM-I).


All patients with CM-I were identified from the 2 largest health care providers in Utah; those patients with linked genealogical data were used to test hypotheses regarding familial clustering. Relative risks (RRs) in first-, second-, and third-degree relatives were estimated using internal cohort-specific CM-I rates; the Genealogical Index of Familiality (GIF) test was used to test for an excess of relationships between all patients with CM-I compared with the expected distribution of relationships for matched control sets randomly selected from the resource. Pedigrees with significantly more patients with CM-I than expected (p < 0.05) based on internal rates were identified.


A total of 2871 patients with CM-I with at least 3 generations of genealogical data were identified. Significantly increased RRs were observed for first- and third-degree relatives (RR 4.54, p < 0.001, and RR 1.36, p < 0.001, respectively); the RR for second-degree relatives was elevated, but not significantly (RR 1.20, p = 0.13). Significant excess pairwise relatedness was observed among the patients with CM-I (p < 0.001), and borderline significant excess pairwise relatedness was observed when all relationships closer than first cousins were ignored (p = 0.051). Multiple extended high-risk CM-I pedigrees with closely and distantly related members were identified.


This population-based description of the familial clustering of 2871 patients with CM-I provided strong evidence for a genetic contribution to a predisposition to CM-I.

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Lisa A. Cannon Albright, Nicola J. Camp, James M. Farnham, Joel Macdonald, Keyvan Abtin and Kerry G. Rowe

Object. This study was conducted to investigate the familial and genetic contribution to intracranial, abdominal aortic, and all other types of aneurysms, and to define familial relationships among patients who present with the different aneurysm types.

Methods. The authors used a unique Utah resource to perform population-based analysis of the familial nature of aneurysms. The Utah Population Data Base is a genealogy of the Utah population dating back eight generations, which is combined with death certificate data for the state of Utah dating back to 1904. Taking into account the genetic relationships among all aneurysm cases derived from this resource, the authors used a previously published method to estimate the familiality of different aneurysm types. Using internal, birth-cohort-specific rates of disease calculated from the database, they estimated relative risks by comparing observed to expected rates of aneurysm incidence in defined sets of relatives of probands.

Conclusions. Each of the three aneurysm types investigated showed significant evidence for a genetic component. Relatives of patients with intracranial aneurysms do not appear to be at increased risk for abdominal or other lesions, but relatives of patients with abdominal aortic aneurysms appear to be at increased risk for other types of these lesions.

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Lisa Anne Cannon-Albright