Body mass index and γ-glutamyl transferase expression in normal and cancerous breast tissue
- 20 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer
- Vol. 27 (5), 850-860
- https://doi.org/10.1007/s12282-020-01080-5
Abstract
Background Localized to cell membrane, γ-glutamyl transferase (GGT) is a reliable marker for the evaluation of cell distress occurring in several pathological conditions including obesity, metabolic syndrome, and cancer. In particular, high GGT serum levels are associated with breast cancer incidence and progression. Methods The tissue expression of GGT1, the gene coding for GGT, was investigated in silico in a large case series of paired samples of breast cancer and adjacent histologically normal (HN) tissue, and in a collection of healthy breast tissues from reduction mammoplasty. The association of GGT1 with patient’s body mass index (BMI), and the relationship between GGT1 and a panel of genes involved in apoptosis, IGF-1 signaling, or coding for adipokines and adipokine receptors were also investigated. Results GGT1 expression was significantly higher in tumor than in the adjacent HN tissue (P = 0.0002). Unexpectedly, the expression of GGT1 was inversely associated with BMI in normal and HN tissue, whereas no correlation was found in cancerous tissue. In all tissues, GGT1 correlated positively with TP53 and negatively with BCL2 and LEPR, whereas only in normal and HN tissue GGT1 correlated positively with IGF1R. The linear regression model, adjusted for BMI, showed no confounding effect on any correlation, except for the correlation of GGT1 with LEPR in normal tissue from healthy women. Conclusions Even if present results provide interesting insights on the still elusive mechanism(s) underlying the association between obesity and epithelial cell proliferation, possibly promoting neoplastic transformation, such relationship deserves further investigation in other independent datasets.Keywords
This publication has 37 references indexed in Scilit:
- Prognostic Relevance of Pretherapeutic Gamma-Glutamyltransferase in Patients with Primary Metastatic Breast CancerPLOS ONE, 2015
- γ-Glutamyl transferase and breast cancer riskBritish Journal of Cancer, 2010
- Hepatic fat content-independent association of the serum level of gamma-glutamyltransferase with visceral adiposity, but not subcutaneous adiposityDiabetes Research and Clinical Practice, 2008
- A Strong Interaction between Serum γ-Glutamyltransferase and Obesity on the Risk of Prevalent Type 2 Diabetes: Results from the Third National Health and Nutrition Examination SurveyClinical Chemistry, 2007
- Gamma Glutamyl Transferase and Metabolic Syndrome, Cardiovascular Disease, and Mortality RiskArteriosclerosis, Thrombosis, and Vascular Biology, 2007
- The role of glutathione in cancerCell Biochemistry and Function, 2004
- Gamma Glutamyl TransferaseCritical Reviews in Clinical Laboratory Sciences, 2001
- Serum Gamma-Glutamyl Transferase, Self-Reported Alcohol Drinking, and the Risk of StrokeStroke, 2000
- The role of glutathione in the regulation of apoptosisEuropean Journal of Clinical Investigation, 1999
- THE TROMSØ STUDYAmerican Journal of Epidemiology, 1990