Metastatic Patterns of Duodenopancreatic Neuroendocrine Tumors in Patients With Multiple Endocrine Neoplasia Type 1

Abstract Context Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease caused by the loss of function of the MEN1 gene, a tumor-suppressor gene that encodes the protein menin. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine tumors (dpNET), pituitary tumors (PIT), adrenal adenomas, and bronchopulmonary (bp-NET), thymic, and gastric neuroendocrine tumors. More insight into factors influencing the age-related penetrance of MEN1 manifestations could provide clues for more personalized screening programs. Objective To investigate whether genetic anticipation plays a role in the largest known MEN1 families in the Netherlands. Methods All Dutch MEN1 families with ≥ 10 affected members in ≥ 2 successive generations were identified. Age at detection of the different MEN1-related manifestations were compared among generations using regression analyses adjusted for competing risks. To correct for the beneficial effect of being under surveillance, manifestations occurring during surveillance were also separately compared. Results A total of 152 MEN1 patients from 10 families were included. A significantly decreased age at detection of pHPT, dpNET, PIT, and bp-NET was found in successive generations (P < 0.0001). Adjusted analyses led to the same results. Conclusions These results suggest the presence of genetic anticipation. However, due to a risk of residual bias, the results must be interpreted with caution. After independent validation in other cohorts and further translational research investigating the molecular mechanisms explaining this phenomenon in MEN1, the results might add to future, more personalized, screening protocols and earlier screening for future generations of MEN1 patients.

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No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-2615 ◽

2015 ◽

Vol 100 (10) ◽

pp. 3850-3855 ◽

Cited By ~ 4

Author(s):

Sjoerd Nell ◽

Rachel S. van Leeuwaarde ◽

Carolina R. C. Pieterman ◽

Joanne M. de Laat ◽

Ad R. Hermus ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Metastatic Disease ◽

Cumulative Incidence ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

Blood Type ◽

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Abo Blood Type

Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood type O was proposed as an additional factor to personalize screening criteria for neuroendocrine tumors in MEN1 patients. Objective: The aim of this study was to assess the association between blood type O and the occurrence of neuroendocrine tumors in the national Dutch MEN1 cohort. Design: This is a cohort study using the Dutch National MEN1 database, which includes more than 90% of the Dutch MEN1 population. Demographic and clinical data were analyzed by blood type. Chi-square tests and Fisher exact tests were used to determine the association between blood type O and occurrence of neuroendocrine tumors. A cumulative incidence analysis (Gray's test) was performed to assess the equality of cumulative incidence of neuroendocrine tumors in blood type groups, taking death into account as a competing risk. Results: The ABO blood type of 200 of 322 MEN1 patients was known. Demographic and clinical characteristics were similar among blood type O and non-O type cohorts. The occurrence of neuroendocrine tumors of the lung, thymus, pancreas, and gastrointestinal tract was equally distributed across the blood type O and non-O type cohorts (Grays's test for equality; P = 0.72). Furthermore, we found no association between blood type O and the occurrence of metastatic disease or survival. Conclusions: An association between blood type O and the occurrence of neuroendocrine tumors in MEN1 patients was not confirmed. For this reason, the addition of the blood type to screening and surveillance practice seems not to be of additional value for identifying MEN1 patients at risk for the development of neuroendocrine tumors, metastatic disease, or a shortened survival.

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