Nakazato Haruki, Suzuki Kazuhiro, Matsui Hiroshi, Koike Hidekazu, Okugi Hironobu, Ohtake Nobuaki, Takei Tomoyuki, Nakata Seiji, Hasumi Masaru, Ito Kazuto, Kurokawa Kohei, Yamanaka Hidetoshi
Department of Urology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.
Anticancer Res. 2003 May-Jun;23(3C):2897-902.
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.
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.
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.
谷胱甘肽 - S - 转移酶(GSTs)在多种毒素和致癌物的解毒过程中发挥作用。已对GSTM1、GSTT1和GSTP1基因的遗传多态性进行研究,以评估各种癌症的相对风险。在本研究中,我们通过开展一项病例对照研究,对81例家族性前列腺癌病例和105例正常对照进行分析,探讨了GST基因多态性与日本人群家族性前列腺癌的关联。
未发现GSTM1和GSTT1基因多态性与家族性前列腺癌风险存在显著关联;然而,GSTP1基因的Val/Val基因型显著增加了风险(比值比 = 9.31,95%置信区间 = 0.47 - 184,p = 0.030)。对这三个基因的基因型进行联合分析表明,存在两种高风险基因型,即GSTM1或GSTT1基因的缺失基因型,或GSP1基因的任何Val基因型,会显著增加前列腺癌风险(比值比 = 2.67,95%置信区间 = 1.08 - 6.59,p = 0.03)。根据病理分级或临床分期对病例进行分层,各层之间无显著差异。
在本研究中,我们发现GSTs的基因型,尤其是GSTP1基因的Val等位基因以及三种基因型的组合,与家族性前列腺癌风险相关。