Comparison of Serum Gamma Glutamyl Transferase Levels between Prostate Cancer Patients and Their Healthy Peers
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Abstract
Background: Prostate cancer (PCa) is the most common cancer affecting men, apart from cutaneous cancers. Serum prostate specific antigen (PSA) levels are frequently used to predict prostate cancer diagnosis. However, many causes (e.g., prostatitis, benign prostate obstruction, urethral catheterization) may cause elevated PSA, in addition to PCa. We aimed to investigate the gamma glutamyl transferase (GGT) levels, a serum biomarker not affected by situations other than cancer causing elevated PSA.
Methods: The study evaluated male patients with prostate biopsy due to high serum PSA levels and/or abnormal digital rectal examination (DRE) examined in Ordu University Education and Research Hospital, Ordu/Turkey urology clinic from April 2019 to April 2021. The patient group in the study included 261 men with PCa diagnosis and the control group included 245 healthy men with normal PSA levels, and no PCa and/or benign prostate obstruction (BPO). The two groups were compared in terms of serum GGT levels.
Results: GGT was significantly low in the PCa group and might be a predictor in terms of PCa (P=0.000). In the malignant (PCa) group, the GGT cut-off value was identified as 21.5 (sensitivity 68.6%, specificity 54.4%).
Conclusion: Serum GGT levels might assist in diagnosis of PCa. However, diagnostic power is weak due to low specificity. There is a need for studies investigating the efficacy of GGT levels for prediction of PCa diagnosis and assessing other parameters alongside GGT.
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2. Cirakoglu A, Benli E, Yuce A (2018). Polyg-amy, sexual behavior in a population under risk for prostate cancer diagnos-tic: an observational study from the Black Sea Region in Turkey. Int Braz J Urol, 44 (4): 704-8.
3. Ayyıldız SN, Ayyıldız A (2014). PSA, PSA derivatves, ProPSA and prostate health index in the diagnosis of prostate can-cer. Turk J Urol, 40 (2): 82-8.
4. Zlota AR, Egawa S, Pushkar D, et al (2014). Prevalence of inflammaton and benign prostatc hyperplasia on autopsy in Asian and Caucasian men. Eur Urol, 66 (4): 619-22.
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6. Benli E, Bayrak A, Cirakoglu A, et al (2017). Comparison of serum acetyl hydrolase (PAF-AH) and paraoxonase 1 (PON1) values between prostate cancer patients and a control group. Kaohsiung J Med Sci, 33 (11): 572-77.
7. Kandirali E, Boran C, Serin E, et al (2007). Associaton of extent and aggressiveness of inflammaton with serum PSA levels and PSA density in asymptomatc pa-tents. Urology, 70 (4): 743-47.
8. Lehrer S, Diamond EJ, Mamkine B, et al (2005). C- reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate can-cer. BJU Int, 95 (7): 961-62.
9. Platz EA, De Marzo AM (2004). Epidemi-ology of inflammation and prostate cancer. J Urol, 171 (2): 36-40.
10. Fleshner NE, Kucuk O (2001). Antoxidant dietary supplements: Ratonale and cur-rent status as chemopreventve agents for prostate cancer. Urology, 57 (4): 90-94.
11. Vaca CE, Wilhelm J, Harms-Ringdahl M (1988). Interacton of lipid peroxidaton products with DNA. Mutat Res, 195 (2): 137-49.
12. Pathak SK, Sharma RA, Mellon JK (2003). Chemopreventon of prostate cancer by diet-derived antoxidant agents and hormonal manipulaton (Review). Int J Oncol, 22 (1): 5-13.
13. Arai K, Yoshida K-I, Komoda T, et al (1990). Comparative studies on the properties of purified gamma-glutamyl transferase from human reproductive system and the kidney. Clin Biochem, 23 (2): 105-12.
14. Whitfield J (2001). Gamma glutamyl trans-ferase. Crit Rev Clin Lab Sci, 38 (4): 263-355.
15. Frierson HF, Jr., Theodorescu D, Mills SE, et al (1997). gamma-Glutamyl transpep-tidase in normal and neoplastic prostate glands. Mod Pathol, 10 (1): 1-6.
16. Hanigan MH, Frierson Jr HF, Swanson PE, et al (1999). Altered expression of gam-ma-glutamyl transpeptidase in human tumors. Hum Pathol, 30 (3): 300-5.
17. Kawakami K, Fujita Y, Matsuda Y, et al (2017). Gamma-glutamyltransferase ac-tivity in exosomes as a potential marker for prostate cancer. BMC Cancer, 17 (1): 316.
18. Kunutsor SK, Laukkanen JA (2017). Gam-ma-glutamyltransferase and risk of pros-tate cancer: Findings from the KIHD prospective cohort study. Int J Cancer, 140 (4): 818-24.
19. Bakthavatsalam S, Sleeper ML, Dharani A, et al (2018). Leveraging gamma-Glutamyl Transferase to Direct Cytotoxicity of Copper Dithiocarbamates against Pros-tate Cancer Cells. Angew Chem Int Ed Engl, 57 (39): 12780-84.
20. Bosco C, Garmo H, Hammar N, et al (2018). Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer diagnosis and secondly diagnosed primary tumours: a prospec-tive study in the Swedish AMORIS co-hort. BMC Cancer, 18 (1): 205.
21. Takemura K, Ito M, Nakanishi Y, et al (2019). Serum gamma-Glutamyltransferase as a Prognostic Bi-omarker in Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide. Anticancer Res, 39 (10): 5773-80.
22. Meister A, Tate SS (1976). Glutathione and related γ-glutamyl compounds: biosyn-thesis and utilization. Annu Rev Biochem, 45: 559-604.
23. Choi J, Liu R-M, Forman HJ (1997). Adapta-tion to oxidative stress: quinone-mediated protection of signaling in rat lung epithelial L2 cells. Biochem Pharmacol, 53 (7): 987-93.
24. Forman HJ, Azzi A (1997). On the virtual existence of superoxide anions in mito-chondria: thoughts regarding its role in pathophysiology. FASEB J, 11 (5): 374-75.
25. Rajpert-De Meyts E, Shi M, Chang M, et al (1992). Transfection with γ-glutamyl transpeptidase enhances recovery from glutathione depletion using extracellular glutathione. Toxicol Appl Pharmacol, 114 (1): 56-62.
26. Dominici S, Paolicchi A, Corti A, et al (2005). Prooxidant Reactions Promoted by Soluble and Cell‐Bound γ‐Glutamyltransferase Activity. Methods Enzymol, 401: 484-501.
27. Zmorzynski S, Swiderska-Kolacz G, Kocz-kodaj D, et al (2015). Significance of Polymorphisms and Expression of En-zyme-Encoding Genes Related to Gluta-thione in Hematopoietic Cancers and Solid Tumors. Biomed Res Int, 2015:853573.
28. Van Hemelrijck M, Jassem W, Walldius G, et al (2011). Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons - the Swedish AMORIS study. Eur J Cancer, 47 (13): 2033-41.
29. Munjal D, Chawla PL, Lokich JJ, et al (1976). Carcinoembryonic antigen and phosphohexose isomerase, gammag-lutamyl transpeptidase and lactate de-hydrogenase levels in patients with and without liver metastases. Cancer, 37 (4):1800-7.
30. Paolicchi A, Pompella A, Tonarelli P, et al (1996). Gamma-glutamyltranspeptidase activity in human ovarian carcinoma. Anticancer Res, 16 (5B): 3053-8.
2. Cirakoglu A, Benli E, Yuce A (2018). Polyg-amy, sexual behavior in a population under risk for prostate cancer diagnos-tic: an observational study from the Black Sea Region in Turkey. Int Braz J Urol, 44 (4): 704-8.
3. Ayyıldız SN, Ayyıldız A (2014). PSA, PSA derivatves, ProPSA and prostate health index in the diagnosis of prostate can-cer. Turk J Urol, 40 (2): 82-8.
4. Zlota AR, Egawa S, Pushkar D, et al (2014). Prevalence of inflammaton and benign prostatc hyperplasia on autopsy in Asian and Caucasian men. Eur Urol, 66 (4): 619-22.
5. Asgari SA, Mohammadi M (2011). The role of intraprostatic inflammaton in the acute urinary retenton. Int J Prev Med, 2 (1): 28-31.
6. Benli E, Bayrak A, Cirakoglu A, et al (2017). Comparison of serum acetyl hydrolase (PAF-AH) and paraoxonase 1 (PON1) values between prostate cancer patients and a control group. Kaohsiung J Med Sci, 33 (11): 572-77.
7. Kandirali E, Boran C, Serin E, et al (2007). Associaton of extent and aggressiveness of inflammaton with serum PSA levels and PSA density in asymptomatc pa-tents. Urology, 70 (4): 743-47.
8. Lehrer S, Diamond EJ, Mamkine B, et al (2005). C- reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate can-cer. BJU Int, 95 (7): 961-62.
9. Platz EA, De Marzo AM (2004). Epidemi-ology of inflammation and prostate cancer. J Urol, 171 (2): 36-40.
10. Fleshner NE, Kucuk O (2001). Antoxidant dietary supplements: Ratonale and cur-rent status as chemopreventve agents for prostate cancer. Urology, 57 (4): 90-94.
11. Vaca CE, Wilhelm J, Harms-Ringdahl M (1988). Interacton of lipid peroxidaton products with DNA. Mutat Res, 195 (2): 137-49.
12. Pathak SK, Sharma RA, Mellon JK (2003). Chemopreventon of prostate cancer by diet-derived antoxidant agents and hormonal manipulaton (Review). Int J Oncol, 22 (1): 5-13.
13. Arai K, Yoshida K-I, Komoda T, et al (1990). Comparative studies on the properties of purified gamma-glutamyl transferase from human reproductive system and the kidney. Clin Biochem, 23 (2): 105-12.
14. Whitfield J (2001). Gamma glutamyl trans-ferase. Crit Rev Clin Lab Sci, 38 (4): 263-355.
15. Frierson HF, Jr., Theodorescu D, Mills SE, et al (1997). gamma-Glutamyl transpep-tidase in normal and neoplastic prostate glands. Mod Pathol, 10 (1): 1-6.
16. Hanigan MH, Frierson Jr HF, Swanson PE, et al (1999). Altered expression of gam-ma-glutamyl transpeptidase in human tumors. Hum Pathol, 30 (3): 300-5.
17. Kawakami K, Fujita Y, Matsuda Y, et al (2017). Gamma-glutamyltransferase ac-tivity in exosomes as a potential marker for prostate cancer. BMC Cancer, 17 (1): 316.
18. Kunutsor SK, Laukkanen JA (2017). Gam-ma-glutamyltransferase and risk of pros-tate cancer: Findings from the KIHD prospective cohort study. Int J Cancer, 140 (4): 818-24.
19. Bakthavatsalam S, Sleeper ML, Dharani A, et al (2018). Leveraging gamma-Glutamyl Transferase to Direct Cytotoxicity of Copper Dithiocarbamates against Pros-tate Cancer Cells. Angew Chem Int Ed Engl, 57 (39): 12780-84.
20. Bosco C, Garmo H, Hammar N, et al (2018). Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer diagnosis and secondly diagnosed primary tumours: a prospec-tive study in the Swedish AMORIS co-hort. BMC Cancer, 18 (1): 205.
21. Takemura K, Ito M, Nakanishi Y, et al (2019). Serum gamma-Glutamyltransferase as a Prognostic Bi-omarker in Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide. Anticancer Res, 39 (10): 5773-80.
22. Meister A, Tate SS (1976). Glutathione and related γ-glutamyl compounds: biosyn-thesis and utilization. Annu Rev Biochem, 45: 559-604.
23. Choi J, Liu R-M, Forman HJ (1997). Adapta-tion to oxidative stress: quinone-mediated protection of signaling in rat lung epithelial L2 cells. Biochem Pharmacol, 53 (7): 987-93.
24. Forman HJ, Azzi A (1997). On the virtual existence of superoxide anions in mito-chondria: thoughts regarding its role in pathophysiology. FASEB J, 11 (5): 374-75.
25. Rajpert-De Meyts E, Shi M, Chang M, et al (1992). Transfection with γ-glutamyl transpeptidase enhances recovery from glutathione depletion using extracellular glutathione. Toxicol Appl Pharmacol, 114 (1): 56-62.
26. Dominici S, Paolicchi A, Corti A, et al (2005). Prooxidant Reactions Promoted by Soluble and Cell‐Bound γ‐Glutamyltransferase Activity. Methods Enzymol, 401: 484-501.
27. Zmorzynski S, Swiderska-Kolacz G, Kocz-kodaj D, et al (2015). Significance of Polymorphisms and Expression of En-zyme-Encoding Genes Related to Gluta-thione in Hematopoietic Cancers and Solid Tumors. Biomed Res Int, 2015:853573.
28. Van Hemelrijck M, Jassem W, Walldius G, et al (2011). Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons - the Swedish AMORIS study. Eur J Cancer, 47 (13): 2033-41.
29. Munjal D, Chawla PL, Lokich JJ, et al (1976). Carcinoembryonic antigen and phosphohexose isomerase, gammag-lutamyl transpeptidase and lactate de-hydrogenase levels in patients with and without liver metastases. Cancer, 37 (4):1800-7.
30. Paolicchi A, Pompella A, Tonarelli P, et al (1996). Gamma-glutamyltranspeptidase activity in human ovarian carcinoma. Anticancer Res, 16 (5B): 3053-8.
| Files | ||
| Issue | Vol 52 No 7 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i7.13251 | |
| Keywords | ||
| Gamma glutamyl transferase Prostate cancer Biomarker Prostate specific antigen | ||
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How to Cite
1.
Yuce A, Keles M, Benli E, Cirakoglu A, Yazici I, Nalbant I. Comparison of Serum Gamma Glutamyl Transferase Levels between Prostate Cancer Patients and Their Healthy Peers. Iran J Public Health. 2023;52(7):1487-1494.
