Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk
Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk
复制标题
DOI：
10.1007/s11255-008-9407-y
复制
发表时间：
2009-03-01
影响因子：
2
通讯作者：
Dimovski, Aleksandar J.
中科院分区：
文献类型：
--
作者：
Arsova-Sarafinovska, Zorica;Matevska, Nadica;Dimovski, Aleksandar J.
谷胱甘肽过氧化物酶1（GPX 1）是一种广泛表达的硒依赖性酶，通过减少过氧化氢和各种有机过氧化物来保护细胞免受氧化损伤。一些流行病学研究已经将低GPX活性或特定的GPX 1多态性与癌症风险增加相关联，尽管这些相关性并没有在所有人群中一致地观察到。因此，我们进行了本研究，以评估可能的关联GPX 1 Pro 198 Leu多态性和红细胞GPX活性与前列腺癌的发展风险，并澄清红细胞GPX活性水平是否与GPX 1 Pro 198 Leu基因型在马其顿人口。在82例前列腺癌病例和123例对照个体中测定GPX 1 Pro 198 Leu基因型。我们发现GPX 1多态性的变异Leu等位基因对前列腺癌风险具有总体保护作用。与纯合子野生型个体相比，变异Leu等位基因的杂合子携带者患前列腺癌的风险显著降低（OR，0.38; 95%CI，0.20-0.75; P = 0.004）。对73例患者和91例对照者进行了红细胞GPX活性测定。癌症组红细胞GPX活性低于健康对照组。此外，我们比较了90名对照组受试者的红细胞GPX活性，发现基因型之间无显著差异。这些研究结果表明，前列腺癌的个体易感性可能是由GPX 1多态性调制和氧化反应与环境致癌物的遗传因素的组合可能在前列腺癌的发生中发挥重要作用。
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.