Glyoxalase 1−419C>A Variant Is Associated with Oxidative Stress: Implications in Prostate Cancer Progression

Abstract

Glyoxalase 1 is a scavenging enzyme of potent precursors in reactive oxygen species formation and is involved in the occurrence and progression of human malignancies. Glyoxalase I A111E polymorphism has been suggested to influence its enzymatic activity. The present study was aimed at investigating the association of this polymorphism with oxidative stress and its implications in prostate cancer progression or survival. The polymorphism was genotyped in human differently aggressive and invasive prostate cancer cell lines, in 571 prostate cancer or 588 benign prostatic hyperplasia patients, and 580 healthy subjects by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism. Glyoxalase 1 activity, the pro-oxidant Glyoxalase 1-related Argpyrimidine and oxidative stress biomarkers were evaluated by biochemical analyses. Glyoxalase 1 polymorphism was associated with an increase in Glyoxalase 1-related pro-oxidant Argpyrimidine and oxidative stress levels and cancer progression. The mutant A allele conferred a modest risk of prostate cancer, a marked risk of prostate cancer progression and a lower survival time, compared to the wild C allele. The results of our exploratory study point out a significant role for Glyoxalase 1 in prostate cancer progression, providing an additional candidate for risk assessment in prostate cancer patients and an independent prognostic factor for survival. Finally, we provided evidence of the biological plausibility of Glyoxalase 1 polymorphism, either alone or in combination with other ones, all related to oxidative stress control that represents a key event in PCa development and progression.

RETRACTED: Glyoxalase 2 drives tumorigenesis in human prostate cells in a mechanism involving androgen receptor and p53‐p21 axis

“…High expression and activity of Glo1 in cancer cells would provide a safeguard for the rapid proliferation of tumor cells by enhancing MG detoxification. In PCa, we and others have consistently demonstrated a major role of Glo1 in the progression of this neoplasia rather than its genesis . While the role of Glo1 has been extensively investigated, very little is known about Glo2, including its role in the glyoxalase system, and its physiological significance in human cancers, including PCa .…”

“…In PCa, we and others have consistently demonstrated a major role of Glo1 in the progression of this neoplasia rather than its genesis. 6,10,11 While the role of Glo1 has been extensively investigated, very little is known about Glo2, including its role in the glyoxalase system, and its physiological significance in human cancers, [12][13][14][15][16] including PCa. 16,17 In the present study, we investigated the role of Glo2 in prostate tumorigenesis, and, consequently, its potential use as marker in the early diagnosis of PCa.…”

Oxidative stress in prostate hyperplasia and carcinogenesis

“…Polymorphism in Glyoxalase I A111E may influence its enzymatic activity. GLO1 could be important in PCa progression and may be a good marker for risk assessment and prognosis in PCa patients [ 137 ]. Another gene, prostate-associated gene 4 (PAGE4) encodes a protein which protects cells against stress by elevating p21 and suppressing ROS production.…”

Glyoxalases in Urological Malignancies

“…In particular, Chavan et al [57] suggested serum Glo1 as a supplemental biomarker to differentiate between malignant and non-malignant diseases of the prostate in patients with PSA in the range of 4-20 ng/ml. Similarly, we first explored the association of Glo1 A111E functional polymorphism, associated with a loss-of-function mutation and for which we demonstrated evidence of a biological plausibility, providing an additional candidate for risk assessment in PCa patients and an independent prognostic factor for survival [58]. Although further investigations with a larger number of participants are absolutely required to confirm these findings, these explorative studies pioneered researches important for PCa diagnosis and encourage further progress in this field.…”