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

Hassan, Manal M.; Phan, Alexandria T.; Li, Donghui; Dagohoy, Cecile G.; Leary, Colleen; Yao, James C.

doi:10.1158/1055-9965.epi-07-0750

Cited by 50 publications

(63 citation statements)

References 30 publications

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“…A family history of cancer appears to be a strong risk factor for development of all types of carcinoids. Ileal carcinoids have been found to be strongly associated with cancers of the gastrointestinal tract and prostate [27]. These data are in line with reports of increased numbers of malignancies in patients with carcinoid disease [18,19,28].…”

Section: Profiling Of Susceptibility Genes For Ileal Carcinoidssupporting

confidence: 81%

Profiling of Ileal Carcinoids

Nilsson

2012

Neuroendocrinology

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Identification of common molecular mechanisms is needed to facilitate the development of new treatment options for patients with ileal carcinoids. Purpose of Review: Recent profiling studies on ileal carcinoids were examined to obtain a comprehensive view of risk factors, genetic aberrations, and transcriptional alterations. Special attention was paid to mechanisms that could provide novel targets for therapy. Results: Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) at IL12A and DAD1 are associated with an increased risk of ileal carcinoids. Genomic profiling revealed distinct patterns of copy-number alterations in ileal carcinoids. Two groups of carcinoids could be identified by hierarchical clustering. A major group of tumors was characterized by loss on chromosome 18 followed by additional losses on chromosomes 3p, 11q, and 13. Three minimal common regions of deletions were identified at 18q21.1–q21.31, 18q22.1–q22.2, and 18q22.3–q23. A minor group of tumors was characterized by clustered gains on chromosomes 4, 5, 7, 14, and 20. Expression profiling identified three groups of ileal carcinoids by principal component analysis. Tumor progression was associated with changes in gene expression including downregulation of MIR133A. Candidate genes for targeted therapy included ERBB2/HER2, DAD1, PRKCA, RYBP, CASP1, CASP4, CASP5, VMAT1, RET, APLP1, OR51E1, GPR112, SPOCK1, RUNX1, and MIR133A.Conclusion: Profiling of ileal carcinoids has revealed recurrent genetic alterations and distinct patterns of gene expression. Frequent alterations in cellular pathways and genes were identified, suggesting novel targets for therapy. Translational studies are needed to validate suggested molecular targets.

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Section: Profiling Of Susceptibility Genes For Ileal Carcinoidssupporting

confidence: 81%

Profiling of Ileal Carcinoids

Nilsson

2012

Neuroendocrinology

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“…Also, a recent case-control study found an increased risk of developing small bowel carcinoids in individuals with a family history of other cancers, in particular colorectal and prostate cancer [15]. …”

Section: Discussionmentioning

confidence: 99%

“…insular, trabecular, glandular, and diffuse growth patterns, respectively. In addition, the recently added ‘solid’ variant was applied [15]. The histopathological and IHC subdivision of the carcinoids with respect to their degree of malignancy followed the WHO classification, i.e.…”

Section: Methodsmentioning

confidence: 99%

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First Report on Metastasizing Small Bowel Carcinoids in First-Degree Relatives in Three Generations

Järhult¹,

Landerholm²,

Falkmer

et al. 2010

Neuroendocrinology

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Background/Aims: There is an established association between the multiple endocrine neoplasia type 1 (MEN 1) syndrome and foregut carcinoids. Some registry studies also indicate that offspring to carcinoid patients run an increased risk of developing a carcinoid tumor themselves. However, there are only scattered reports of gastrointestinal carcinoids in two generations. The aim of this study was to describe the clinical characteristics as well as the histopathological, immunohistochemical (IHC) and genetic data of metastasizing ileal carcinoids in three consecutive first-degree relatives. Methods: The histopathological and IHC analyses were performed on newly cut sections of the tumor specimens and included growth pattern, proliferation index (Ki-67) as well as expression of established neuroendocrine markers and recently introduced cocaine-amphetamine-regulated transcript (CART). The genetic analyses were focused on establishing whether a connection with the MEN 1 syndrome existed in this family, by means of mutation screening using polymerase chain reaction, multiple ligation-dependent probe amplification, and genotyping using fluorescent-labeled microsatellite markers. Results: Histopathology and IHC revealed that the tumors were virtually identical, with only minor differences in proliferation index and expression of CART. Genetic analyses indicated that the inheritance of the small bowel carcinoids in the family was not linked to the MEN1 gene. Conclusion: Metastasizing small bowel carcinoids have been found in first-degree relatives in three consecutive generations. All three tumors were very similar when characterized by histopathology and IHC. Based on clinical findings and genetic analyses, it seems unlikely, although not completely excluded, that inheritance was linked to the MEN 1 syndrome.

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“…Выполнение лимф-аденэктомии достоверно улучшает общую выживаемость. Адекватным объемом лимфо-диссекции при НЭО тонкой кишки, по мне-нию некоторых авторов, необходимо считать удаление как минимум 8 лимфатических узлов [64][65][66][67][68][69][70][71][72][73][74][75][76].…”

Section: хирургическое лечениеunclassified

Radionuclide imaging and therapy in patients with neuroendocrine tumors

et al. 2018

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Нейроэндокринные опухоли представляют собой гетерогенную группу опухолей, возникающих из энтерохром-аффинных клеток диффузной нейроэндокринной системы и встречающихся в 0,5% случаев всех новообразований. За последние годы отмечается значительный рост заболеваемости нейроэндокринными опухолями, что безуслов-но связано с усовершенствованием методов их диагностики. Однако, несмотря на значительные успехи в изучении биологических и молекулярных механизмов поведения данной группы заболеваний, формирование единого алго-ритма диагностики и лечения нейроэндокринных опухолей остается затруднительным и по сей день. Лечение нейроэндокринных опухолей во многом зависит от их функционального статуса и стадии заболевания. Наиболее предпочтительным подходом в лечении локализованных форм нейроэндокринных опухолей остается хирургиче-ский. В то же время для больных с распространенными процессами, характеризующимися наличием отдаленных метастазов, на сегодняшний день доступен широкий спектр терапевтических стратегий. Среди них можно выде-лить контроль над синдромами, ассоциированными с гиперсекрецией тех или иных гормонов, выполнение цито-редуктивных вмешательств, системную химиотерапию, применение аналогов соматостатина, а также радиотар-гетную терапию. Однако алгоритм выбора того или иного терапевтического подхода в современной клинической практике у разнородной группы больных с нейроэндокринными опухолями требует дальнейшего обсуждения. Ключевые слова: нейроэндокринные опухоли, радионуклидная диагностика, радиотаргетная терапия, аналоги соматостатина, октреотид, онкология, радиология.Neuroendocrine tumors (NETs) are heterogeneous group of the tumors that arise from the enterochromaffin cells of the diffuse neuroendocrine system and occurr in 0.5% of all neoplasms. Recently there has been a significant increase in the incidence of neuroendocrine tumors, which is undoubtedly associated with the improvement of diagnostic methods. However, despite significant success in studying the biological and molecular mechanisms of its behavior, a single algorithm for the diagnosis and treatment of neuroendocrine tumors remains unclear today. Treatment of neuroendocrine tumors largely depends on their functional status and the stage of the disease. While the treatment of localized NETs is surgical resection, varieties of therapeutic options are available for patients with advanced NETs. These include medical control of excess hormone levels and associated symptoms, cytoreductive surgery for patients with advanced disease, systemic chemotherapy, somatostatin analogues, and peptide receptor-targeted radionuclide therapy. However, the right choice of the therapeutic approach in current clinical practice in heterogeneous group of patients with neuroendocrine tumors requires further discussion.

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

Cited by 50 publications

References 30 publications

Profiling of Ileal Carcinoids

Profiling of Ileal Carcinoids

First Report on Metastasizing Small Bowel Carcinoids in First-Degree Relatives in Three Generations

Radionuclide imaging and therapy in patients with neuroendocrine tumors

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