Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant.
OBJECTIVE
The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder were tested.


METHODS
Genotypes of the leucine (Leu) to proline (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val) polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56 of MnSOD were determined by a polymerase chain reaction-restriction fragment length polymorphism technique in 213 patients and 209 normal controls.


RESULTS
There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p = 0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18, p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided no significant results. However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024).


CONCLUSIONS
The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer.
Ichimura
Yasushi
Y
Department of Urology, Akita University School of Medicine, Hondo, Japan.
Habuchi
Tomonori
T
Tsuchiya
Norihiko
N
Wang
Lizhong
L
Oyama
Chikara
C
Sato
Kazunari
K
Nishiyama
Hiroyuki
H
Ogawa
Osamu
O
Kato
Tetsuro
T
D000368:Aged; D000409:Alanine / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D014633:Valine / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1
D011392:Proline; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D007930:Leucine; D014633:Valine; D000409:Alanine; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human