Cancer in Ecuadorian subjects with Laron syndrome (ELS)

Jaime Guevara-Aguirre, Gabriela Peña, Gabriel Pazmiño, William Acosta, Jannette Saavedra, Daniela Lescano, Alexandra Guevara, Antonio W.D. Gavilanes

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Resumen

Meta-analyses from 2018-2022 have shown that obesity increases the risk of various cancers such as acute myeloid lymphoma, chronic myeloid lymphoma, diffuse beta cell lymphoma, Hodgkin's lymphoma, leukemia, multiple myeloma, non-Hodgkin's lymphoma, bladder, breast, cholangiocarcinoma, colorectal, ovarian, esophageal, kidney, liver, prostate, thyroid, and uterus. Contextually, obesity, and its comorbidities, is the largest, most lethal pandemics in the history of mankind; hence, identification of underlying mechanisms is needed to adequately address this global health threat. Herein, we present the metabolic and hormonal mechanisms linked to obesity that might etiologically contribute to neoplasia, including hyperinsulinemia and putative places in the insulin-signaling pathway. Excess insulin, acting as a growth factor, might contribute to tumorigenesis, while abundant ATP and GDP supply the additional energy needed for proliferation of rapidly dividing cells. Our observations in the Ecuadorian cohort of subjects with Laron syndrome (ELS) prove that obesity does not always associate with increased cancer risk. Indeed, despite excess body fat from birth to death, these individuals display a diminished incidence of cancer when compared to their age- and sex-matched relatives. Furthermore, in cell cultures exposed to potent oxidizing agents, addition of ELS serum induces less DNA damage as well as increased apoptosis. ELS individuals have absent growth hormone (GH) counter-regulatory effects in carbohydrate metabolism due to a defective GH receptor. The corresponding biochemical phenotype includes extremely low basal serum concentrations of insulin and insulin-like growth factor-I, lower basal glucose and triglyceride (TG) levels, and diminished glucose, TG, and insulin responses to orally administered glucose or to a mixed meal.

Idioma originalInglés
Número de artículoe220389
PublicaciónEndocrine-Related Cancer
Volumen30
N.º6
DOI
EstadoPublicada - 11 may. 2023

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