THE ASSOCIATION OF SOD2 AND GST GENE POLYMORPHISM WITH THE RISK OF DEVELOPMENT AND PROGNOSIS OF PAPILLARY RENAL CELL CARCINOMA
Abstract
Introduction: Redox imbalance is an important factor in both carcinogenesis and progression of renal cell carcinoma. Many studies are focused on finding potential biomarkers that can aid in early detection, as well as in monitoring disease progression. Among the candidates are genes coding for antioxidant enzymes - superoxide dismutase 2 (SOD2) and glutathione S -transferase (GST).
Aim: This study aims to assess the role of SOD2 and GST genes polymorphisms in as risk biomarkers for papillary renal cell carcinoma (pRCC), along with their impact on the survival of these patients.
Materials and methods: This study included 39 patients and 336 controls. SOD2 (rs4880), GSTA1C69T, GSTM1, GSTT1, and GSTP1 (rs1695) polymorphisms were determined by appropriate PCR methods. 8-hydroxy-2′-deoxyguanosine (8-OHdG) and benzo(a)pyrene diol epoxide (BPDE)-DNA adducts plasma level was measured by ELISA method. The effect of the polymorphisms on postoperative prognosis was examined using the available survival data.
Results: There was no significant difference in the distribution of SOD2, GSTA1, GSTM1, and GSTT1 gene variants between patients and controls (p > 0.05). However GSTP1 variant (GSTP1 * IleVal + ValVal) genotype was statistically significantly more frequent in patients compared to controls (p < 0.05). Similarly, carriers of GSTP1 variant genotype were at significantly higher risk of developing carcinoma compared to carriers of GSTP1 reference genotype (OR = 16.103, 95% IP = 2.036 - 127.398). There was no association between the level of both 8-OHdG and BPDE-DNA adducts, and different genotypes (p > 0.05). The investigated polymorphisms did not show any prognostic significance (p > 0.05).
References
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin [Internet]. 2018 Nov [cited 2021 Feb 19];68(6):394–424. Available from: https://pubmed.ncbi.nlm.nih.gov/30207593/
- Linehan WM, Ricketts CJ. The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications [Internet]. Vol. 16, Nature Reviews Urology. Nature Publishing Group; 2019 [cited 2021 Feb 19]. p. 539–52. Available from: https://pubmed.ncbi.nlm.nih.gov/31278395/
- Steffens S, Janssen M, Roos FC, Becker F, Schumacher S, Seidel C, et al. Incidence and long-term prognosis of papillary compared to clear cell renal cell carcinoma - A multicentre study. Eur J Cancer [Internet]. 2012 Oct 1 [cited 2021 Feb 20];48(15):2347–52. Available from: http://dx.doi.org/10.1016/j.ejca.2012.05.002
- Xiao Y, Meierhofer D. Glutathione metabolism in renal cell carcinoma progression and implications for therapies. Int J Mol Sci [Internet]. 2019 Aug 1 [cited 2021 Feb 20];20(15):1–20. Available from: /pmc/articles/PMC6696504/
- U C, K B, A B, SA B, F B, J C, et al. Epidemiology of Renal Cell Carcinoma. Eur Urol [Internet]. 2019 Jan 1 [cited 2021 Sep 24];75(1):74–84. Available from: https://pubmed.ncbi.nlm.nih.gov/30243799/
- Capitanio U, Montorsi F. Renal cancer. In: The Lancet [Internet]. Lancet Publishing Group; 2016 [cited 2021 Mar 5]. p. 894–906. Available from: https://pubmed.ncbi.nlm.nih.gov/26318520/
- Board PG, Menon D. Glutathione transferases, regulators of cellular metabolism and physiology. Biochim Biophys Acta - Gen Subj. 2013 May 1;1830(5):3267–88.
- Sutton A, Imbert A, Igoudjil A, Descatoire V, Cazanave S, Pessayre D, et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics [Internet]. 2005 [cited 2021 Mar 6];15(5):311–9. Available from: https://pubmed.ncbi.nlm.nih.gov/15864132/
- JD H, RC S. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology [Internet]. 2000 [cited 2021 Sep 24];61(3):154–66. Available from: https://pubmed.ncbi.nlm.nih.gov/10971201/
- RC S, PW J, AA F. Glutathione S-transferase: genetics and role in toxicology. Toxicol Lett [Internet]. 2000 Mar 15 [cited 2021 Sep 19];112–113:357–63. Available from: https://pubmed.ncbi.nlm.nih.gov/10720752/
- Mihailovic S, Coric V, Radic T, Radojevic AS, Matic M, Dragicevic D, et al. The Association of Polymorphisms in Nrf2 and Genes Involved in Redox Homeostasis in the Development and Progression of Clear Cell Renal Cell Carcinoma. Oxid Med Cell Longev. 2021;2021.
- VM C, TP S, TD P, GM B-J, AR S-R, SM R-S, et al. GSTM1 genotype is an independent prognostic factor in clear cell renal cell carcinoma. Urol Oncol [Internet]. 2017 Jun 1 [cited 2021 Sep 19];35(6):409–17. Available from: https://pubmed.ncbi.nlm.nih.gov/28284893/
- Ćorić C, Ćorić V, Plješa-Ercegovac M, Džamić Z. The role of glutathione transferases in renal cell carcinoma. Med Podml. 2016;67(3):42–8.
- JR S, B D, JN E, L E, JI E, D G, et al. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J Surg Pathol [Internet]. 2013 [cited 2021 Sep 24];37(10):1469–89. Available from: https://pubmed.ncbi.nlm.nih.gov/24025519/
- Coles B, Nowell SA, MacLeod SL, Sweeney C, Lang NP, Kadlubar FF. The role of human glutathione S-transferases (hGSTs) in the detoxification of the food-derived carcinogen metabolite N-acetoxy-PhIP, and the effect of a polymorphism in hGSTA1 on colorectal cancer risk. Mutat Res - Fundam Mol Mech Mutagen. 2001 Oct 1;482(1–2):3–10.
- SZ A-R, RA el-Z, WA A, WW A. A multiplex PCR procedure for polymorphic analysis of GSTM1 and GSTT1 genes in population studies. Cancer Lett [Internet]. 1996 Oct 22 [cited 2021 Sep 19];107(2):229–33. Available from: https://pubmed.ncbi.nlm.nih.gov/8947518/
- Pljesa-Ercegovac M, Mimic-Oka J, Dragicevic D, Savic-Radojevic A, Opacic M, Pljesa S, et al. Altered antioxidant capacity in human renal cell carcinoma: Role of glutathione associated enzymes. Urol Oncol Semin Orig Investig [Internet]. 2008 Mar 26 [cited 2021 Mar 5];26(2):175–81. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1078143907000294
- Coric VM, Simic TP, Pekmezovic TD, Basta-Jovanovic GM, Radojevic ARS, Radojevic-Skodric SM, et al. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma. PLoS One [Internet]. 2016 Aug 1 [cited 2021 Sep 29];11(8):e0160570. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160570
- Alavanja M, Baron JA, Brownson RC, Buffler PA, DeMarini DM, Djordjevic M V., et al. Tobacco smoke and involuntary smoking. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans [Internet]. International Agency for Research on Cancer; 2004 [cited 2021 Mar 5]. p. 1–1413. Available from: /pmc/articles/PMC4781536/
- Atilgan D, Parlaktas BS, Uluocak N, Kolukcu E, Erdemir F, Ozyurt H, et al. The relationship between ALA16VAL single gene polymorphism and renal cell carcinoma. Adv Urol. 2014;2014.
- Dasgupta J, Subbaram S, Connor KM, Rodriguez AM, Tirosh O, Beckman JS, et al. Manganese superoxide dismutase protects from TNF-α-induced apoptosis by increasing the steady-state production of H2O2. Antioxidants Redox Signal [Internet]. 2006 Jul [cited 2021 Mar 6];8(7–8):1295–305. Available from: https://pubmed.ncbi.nlm.nih.gov/16910777/
- E K, M H, K B, K G, VN K, RJ H, et al. Pooled analysis and meta-analysis of the glutathione S-transferase P1 Ile 105Val polymorphism and bladder cancer: a HuGE-GSEC review. Am J Epidemiol [Internet]. 2007 Jun [cited 2021 Sep 29];165(11):1221–30. Available from: https://pubmed.ncbi.nlm.nih.gov/17404387/
- De Martino M, Klatte T, Schatzl G, Remzi M, Waldert M, Haitel A, et al. Renal Cell Carcinoma Fuhrman Grade and Histological Subtype Correlate With Complete Polymorphic Deletion of Glutathione S-Transferase M1 Gene. J Urol. 2010 Mar;183(3):878–83.
- D R, V S, A H, DH P, LW H, CR W, et al. Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis [Internet]. 1997 Jul [cited 2021 Sep 29];18(7):1285–9. Available from: https://pubmed.ncbi.nlm.nih.gov/9230269/
- Zhu Y, Horikawa Y, Yang H, Wood CG, Habuchi T, Wu X. BPDE-Induced Lymphocytic Chromosome 3p Deletions May Predict Renal Cell Carcinoma Risk. J Urol [Internet]. 2008 Jun [cited 2021 Sep 19];179(6):2416. Available from: /pmc/articles/PMC2810745/
- Miyake H, Hara I, Kamidono S, Eto H. Prognostic significance of oxidative DNA damage evaluated by 8-hydroxy-2′-deoxyguanosine in patients undergoing radical nephrectomy for renal cell carcinoma. Urology [Internet]. 2004 Nov [cited 2021 Mar 6];64(5):1057–61. Available from: https://pubmed.ncbi.nlm.nih.gov/15533518/
- A J, U B, T P, M C, M A, Z D, et al. Partial versus radical nephrectomy for pT1a renal cancer in Serbia. J BUON [Internet]. 2016 Nov 1 [cited 2021 Sep 29];21(6):1449–53. Available from: https://europepmc.org/article/med/28039706
- Searchfield L, Price SA, Betton G, Jasani B, Riccardi D, Griffiths DFR. Glutathione S-transferases as molecular markers of tumour progression and prognosis in renal cell carcinoma. Histopathology. 2011 Jan;58(2):180–90.