Context: An increased prevalence of acromegaly was found some years ago in a highly polluted area in North-Eastern Sicily, where high concentration of non-methanic hydrocarbons, volatile organic compounds and cadmium was found. Aryl hydrocarbon receptor (AHR) pathway has a key-role in detoxification of these compounds and in tumorigenesis. Objective: We correlated the occurrence of AHR and/or AHR interacting protein (AIP) genes vari- ants with acromegaly severity, according to pollution exposition. Design: Observational, perspective study conducted over 7 years. Setting: Four Italian referral centers for pituitary diseases. Patients: 210 patients with acromegaly have been enrolled from 2008 and 2015. Interventions: Genetic screening of patients for AHR and AIP variants. Main outcome Measures: Clinical, biochemical and radiological data of patients with and without AIP and/or AHR genes variants, living in polluted (HR) or non polluted (NP) areas of five Italian regions were evaluated and compared. Results:Amongthe23 patients fromHRareas, 9showedAHRor AIPvariants.MeanIGF-1 levels and pituitary tumor diameter were significantly higher in these 9 patients (HR/VAR⫹ve) than in the other 14 (HR/VAR-ve) and in the 187 from NP areas (44 NP/VAR⫹ve). Somatostatin analogs (SSa) significantly decreased mean GH and IGF-1 levels in patients from NP areas and in HR/VAR-ve (GH p⬍0.05; IGF-1xULN p⬍0.01) but not in HR/VAR⫹ve group. Conclusions: Genetic variants potentially inducing functional abnormalities of the AHR pathway are associated with a more severe acromegaly, increased pituitary tumor size and SSa resistance in patients living in highly polluted areas.

Acromegaly Is More Severe in Patients With AHR or AIP Gene Variants Living in Highly Polluted Areas

SCARONI, CARLA;OCCHI, GIANLUCA;CECCATO, FILIPPO;REGAZZO, DANIELA;
2016

Abstract

Context: An increased prevalence of acromegaly was found some years ago in a highly polluted area in North-Eastern Sicily, where high concentration of non-methanic hydrocarbons, volatile organic compounds and cadmium was found. Aryl hydrocarbon receptor (AHR) pathway has a key-role in detoxification of these compounds and in tumorigenesis. Objective: We correlated the occurrence of AHR and/or AHR interacting protein (AIP) genes vari- ants with acromegaly severity, according to pollution exposition. Design: Observational, perspective study conducted over 7 years. Setting: Four Italian referral centers for pituitary diseases. Patients: 210 patients with acromegaly have been enrolled from 2008 and 2015. Interventions: Genetic screening of patients for AHR and AIP variants. Main outcome Measures: Clinical, biochemical and radiological data of patients with and without AIP and/or AHR genes variants, living in polluted (HR) or non polluted (NP) areas of five Italian regions were evaluated and compared. Results:Amongthe23 patients fromHRareas, 9showedAHRor AIPvariants.MeanIGF-1 levels and pituitary tumor diameter were significantly higher in these 9 patients (HR/VAR⫹ve) than in the other 14 (HR/VAR-ve) and in the 187 from NP areas (44 NP/VAR⫹ve). Somatostatin analogs (SSa) significantly decreased mean GH and IGF-1 levels in patients from NP areas and in HR/VAR-ve (GH p⬍0.05; IGF-1xULN p⬍0.01) but not in HR/VAR⫹ve group. Conclusions: Genetic variants potentially inducing functional abnormalities of the AHR pathway are associated with a more severe acromegaly, increased pituitary tumor size and SSa resistance in patients living in highly polluted areas.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3188197
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 28
  • ???jsp.display-item.citation.isi??? 24
social impact