Dataset Information

Association between glutathione peroxidase-1 (GPX1) Rs1050450 polymorphisms and cancer risk.

ABSTRACT: Glutathione peroxidase (GPX), one of the antioxidant enzymes, exerts a vital role in reducing oxidative damage. GPX1 Pro198Leu (rs1050450) polymorphism has been reported in the development of several cancers, while the results were inconsistent. We thus conducted this meta-analysis to identify the association between GPX1 (rs1050450) polymorphism and cancer risk. 52 eligible publications with 60 case-control studies were included, with 21,296 cancer patients and 30,346 controls. The results in total population suggested there was a significant association between GPX1 (rs1050450) polymorphism and cancer susceptibility in part genetic models (TT vs CT+CC: OR = 1.15, 95% CI = 1.01-1.32, P = 0.042; TT vs CC: OR = 1.15, 95% CI = 1.00-1.31, P = 0.044; T vs C: OR = 1.09, 95% CI = 1.01-1.17, P = 0.02). The stratified analysis by cancer types suggested a positive correlation between GPX1 (rs1050450) polymorphism and the development of bladder cancer (TT+CT vs CC: OR = 1.72, 95% CI = 1.09-2.70, P = 0.019; TT vs CT+CC: OR = 3.56, 95% CI = 1.42-8.94, P = 0.007; TT vs CC: OR = 3.75, 95% CI = 1.41-9.94, P = 0.008; T vs C: OR = 1.941, 95% CI = 1.17-3.22, P = 0.01) as well as head and neck cancer (TT vs CT+CC: OR = 2.19, 95% CI = 1.39-3.46, P = 0.001) and brain cancer (TT+CT vs CC: OR = 1.19, 95% CI = 1.03-1.37, P = 0.018). These results support that GPX1 (rs1050450) polymorphism might be a candidate marker for cancer risk with type-specific effects.

SUBMITTER: Wang C

PROVIDER: S-EPMC6965984 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association between glutathione peroxidase-1 (GPX1) Rs1050450 polymorphisms and cancer risk.

Wang Chengdi C Zhang Rui R Chen Nan N Yang Lan L Wang Yinsu Y Sun Yan Y Huang Lin L Zhu Min M Ji Yulin Y Li Weimin W

International journal of clinical and experimental pathology 20170901 9

Glutathione peroxidase (GPX), one of the antioxidant enzymes, exerts a vital role in reducing oxidative damage. GPX1 Pro198Leu (rs1050450) polymorphism has been reported in the development of several cancers, while the results were inconsistent. We thus conducted this meta-analysis to identify the association between GPX1 (rs1050450) polymorphism and cancer risk. 52 eligible publications with 60 case-control studies were included, with 21,296 cancer patients and 30,346 controls. The results in t ...[more]

PMID: 31966829

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Project description:Background and Objectives: Oxidative stress induced by increased reactive oxygen species (ROS) production plays an important role in carcinogenesis. The entire urinary tract is continuously exposed to numerous potentially mutagenic environmental agents which generate ROS during their biotransformation. In first line defense against free radicals, antioxidant enzymes superoxide dismutase (SOD2) and glutathione peroxidase (GPX1) both have essential roles. Altered enzyme activity and decreased ability of neutralizing free oxygen radicals as a consequence of genetic polymorphisms in genes encoding these two enzymes are well described so far. This study aimed to investigate the association of GPX1 (rs1050450) and SOD2 (rs4880) genetic variants with the urothelial bladder cancer (UBC) risk independently and in combination with smoking. Furthermore, we aimed to determine whether the UBC stage and pathological grade were influenced by GPX1 and SOD2 polymorphisms. Material and Methods: The study population included 330 patients with UBC (mean age 65 ± 10.3 years) and 227 respective controls (mean age 63.4 ± 7.9 years). Single nucleotide polymorphism (SNP) of GPX1 (rs1050450) was analyzed using the PCR-RFLP, while SOD2 (rs4880) SNP was analyzed using the q-PCR method. Results: Our results showed that UBC risk was significantly increased among carriers of at least one variant SOD2 Val allele compared to the SOD2 Ala16Ala homozygotes (OR = 1.55, p = 0.03). Moreover, this risk was even more pronounced in smokers with at least one variant SOD2 Val allele, since they have even 7.5 fold higher UBC risk (OR = 7.5, p < 0.001). Considering GPX1 polymorphism, we have not found an association with UBC risk. However, GPX1 genotypes distribution differed significantly according to the tumor stage (p ˂ 0.049) and pathohistological grade (p ˂ 0.018). Conclusion: We found that SOD2 genetic polymorphism is associated with the risk of UBC development independently and in combination with cigarette smoking. Furthermore, we showed that GPX1 genetic polymorphism is associated with the aggressiveness of the disease.

Project description:Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer.We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry.Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r?=?0.3043; p?=?0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype).GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.

Dataset Information

Association between glutathione peroxidase-1 (GPX1) Rs1050450 polymorphisms and cancer risk.

Publications

Association between glutathione peroxidase-1 (GPX1) Rs1050450 polymorphisms and cancer risk.

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