Association of genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) with familial prostate cancer risk in a Japanese population.
BACKGROUND
Glutathione-S-transferases (GSTs) are active in the detoxification of a wide variety of toxins and carcinogens. The genetic polymorphisms of GSTM1, GSTT1 and GSTP1 genes have been studied to estimate the relative risk of various cancers. In the current study, we examined the association of the GST gene polymorphisms with familial prostate cancer in a Japanese population by performing a case-control study consisting of 81 familial prostate cancer cases and 105 normal controls.


METHODS
No significant association of the GSTM1 and GSTT1 gene polymorphisms with familial prostate cancer risk was found; however, the Val/Val genotype of the GSTP1 gene significantly increased risk (OR = 9.31, 95% CI = 0.47-184, p = 0.030). The combination analysis of genotypes of the three genes showed that presence of two high-risk genotypes, i.e., null genotype of the GSTM1 or GSTT1 gene, or any Val genotypes of the GSP1 gene, significantly increased the risk of prostate cancer (OR = 2.67, 95% CI = 1.08-6.59, p = 0.03). Stratification of cases according to the pathological grade or the clinical stage showed no significant differences among categories.


CONCLUSIONS
In the present study, we found that genotypes of GSTs, especially the Val-allele of the GSTP1 gene and the combination of three genotypes, were associated with familial prostate cancer risk.
Nakazato
Haruki
H
Department of Urology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.
Suzuki
Kazuhiro
K
Matsui
Hiroshi
H
Koike
Hidekazu
H
Okugi
Hironobu
H
Ohtake
Nobuaki
N
Takei
Tomoyuki
T
Nakata
Seiji
S
Hasumi
Masaru
M
Ito
Kazuto
K
Kurokawa
Kohei
K
Yamanaka
Hidetoshi
H
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human