Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk.
Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20-0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis.
Department of Drug Quality Control, Republic Institute for Health Protection, Skopje, Republic of Macedonia.
Zorica
Z
Arsova-Sarafinovska
Nadica
N
Matevska
Ayse
A
Eken
Daniel
D
Petrovski
Saso
S
Banev
Sonja
S
Dzikova
Vladimir
V
Georgiev
Aleksandar
A
Sikole
Onur
O
Erdem
Ahmet
A
Sayal
Ahmet
A
Aydin
Aleksandar J
AJ
Dimovski
D000368:Aged; D000369:Aged, 80 and over; D004912:Erythrocytes / Q000201:enzymology*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D012307:Risk Factors; D000094765:Glutathione Peroxidase GPX1
D005979:Glutathione Peroxidase; D005978:Glutathione; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human