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.