Glutathione transferase genotypes may serve as determinants of risk and prognosis in renal cell carcinoma. (4th September 2019)

• Record Type: Journal Article
• Authors: Pljesa‐Ercegovac, Marija; Savic‐Radojevic, Ana; Coric, Vesna; Radic, Tanja; Simic, Tatjana
• Other Names: Korac Bato guestEditor.; Galli Francesco guestEditor.
• Is Part Of: BioFactors. Volume 46:Number 2(2020)
• Page Start: 229
• Page End: 238
• Publication Date: 2019-09-04
• Subjects: glutathione transferases -- polymorphism -- redox homeostasis -- renal cell carcinoma -- risk; Vitamins -- Physiological effect -- Periodicals; Trace elements -- Physiological effect -- Periodicals; Growth factors -- Physiological effect -- Periodicals; Plant growth promoting substances -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Nutritional Physiological Phenomena -- Periodicals; Trace Elements -- metabolism -- Periodicals; Vitamins -- metabolism -- Periodicals; Molecular Biology -- Periodicals; 612.399
• DOI: 10.1002/biof.1560
• Languages: English
• ISSNs: 0951-6433

Abstract

Abstract: Renal cell carcinoma (RCC) represents a group of histologically similar neoplasms with significant intratumor and intertumor genetic heterogeneity. Recognized risk factors for RCC development include smoking, hypertension, obesity, as well as von Hippel–Lindau (VHL) disease. Inactivation of VHL, deregulated nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) pathway, and altered redox homeostasis, together with changes in glutathione transferase (GST) profile, are considered as important contributing factors in RCC development and progression. Although the available results of both gene–gene and gene–environment analysis are quite heterogeneous, they clearly indicate that certain GST genotypes may play a role as risk modifiers, either individually or in combination with other Phase I or Phase II gene polymorphisms, as well as in subjects exposed to relevant substrates. Seemingly, GST genotyping could identify individuals with impaired detoxification in renal parenchyma that are at higher risk of developing RCC. In addition to well established roles of GSTs in conjugation and biotransformation of xenobiotics, GSTs have emerged as significant regulators of pathways determining cell proliferation and survival. Indeed, there are evidence in favor of GST significance, not only in terms of risk for RCC development, but also with respect to progression and prognosis. So far, GS TM1‐active genotype was confirmed to be an independent predictor of higher risk of overall mortality. Therefore, it is reasonable to assume that certain GST variants may assist in individual RCC risk assessment, as well as postoperative prognosis. Even more, GST profiling might contribute to development of personalized targeted therapy in RCC patients.