Glyoxalase 1 -419C>A gene polymorphism: susceptibility factor for prostate cancer?

Polymorphic genes have been identified in Prostate Cancer (PCa) etiology and progression. However, their clinical relevance remains to be fully elucidated. Oxidative stress and inflammation contribute to promotion and progression of tumors, including PCa. Glyoxalase 1 (GLO1) is a scavenging enzyme involved in the detoxification of potent pro-oxidative and pro-inflammatory molecules. In the present study we evaluated the association of GLO1 -419C>A polymorphism with PCa risk in 571 PCa and 588 Benign Prostatic Hyperplasia patients, and its biological/functional significance in human poorly aggressive LNCaP and invasive PC3 prostate cancer cells. We found that the mutant A allele conferred a modest but significant risk of PCa occurrence (OR = 1.34, 95% CI = 1.06-1.70, P = 0.013), a dramatic risk of PCa progression, evaluated by tumor stage (localized: OR = 1.57, 95% CI = 1.16 - 2.12, P = 0.002; locally advanced OR = 8.97, 95% CI = 5.77 - 14.02, P < 0.0001) and histological grading (low grade: OR = 1.46, 95% CI = 1.07-1.98, P = 0.013; moderate grade OR = 7.20, 95% CI = 4.28-12.20, P < 0.0001; high grade: OR = 10.28, 95% CI = 5.64 - 19.05, P < 0.0001), and a lower survival time, compared to the wild C allele. The observed modifications in GLO1 enzymatic activity and GLO1-related genotoxic molecules in LNCaP and PC3 cells, pointed out the functional and biological significance of the polymorphism. Since this is the first study examining the association between GLO1 -419C>A polymorphism and PCa, additional research is required.