The rs1050450 C &gt; T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis

Men, Tongyi; Zhang, Xiaoming; Yang, Jiwei; Shen, Bin; Li, Xianduo; Chen, Dongdong; Wang, Jianning

doi:10.1007/s13277-013-1035-1

Cited by 24 publications

(18 citation statements)

References 29 publications

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“…GPX1 is located on chromosome position 3p21 and contains a genetic polymorphism (rs1050450) that results in either a proline (Pro) or leucine (Leu) at codon 198, described to be a risk factor for the development of various cancers, including lung cancer (Lee et al., ), prostate cancer, (Liwei, Wei, & Ruifa, ; Parlaktas, Atilgan, Gencten, Benli, & Ozyurt, ) and bladder cancer (Men, Zhang, Yang, & Shen, ; Paz‐y‐Mino et al., ).…”

Section: Introductionmentioning

confidence: 99%

Association between glutathione peroxidase 1 codon 198 variant and the occurrence of breast cancer in Rwanda

Habyarimana

Bakri

Mugenzi

et al. 2018

Molec Gen & Gen Med

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BackgroundGlutathione peroxidase 1 gene (GPX1) is one of the antioxidant enzyme that remove the reactive oxygen species in a continuous process. Since the identification of a well‐characterized functional polymorphism named p.Pro198Leu (rs1050450 C>T) in GPX1 gene, abundant studies have evaluated the association between p.Pro198Leu polymorphism and tumor risk in diverse population. But, the available results related to breast cancer are conflicting and absent in Africa. The present case–control study was planned to assess the presence of GPX1 Pro198Leu polymorphism in Rwanda population to determine whether it is associated with the risk of developing breast cancer.MethodsGenomic DNA from peripheral blood leukocytes of 41 patients with breast cancer and 42 healthy controls were enrolled and genotyped GPX1 Pro198Leu polymorphism by PCR amplification and DNA sequencing.ResultsNo significant difference in the frequencies of Pro/Pro (49%) and Pro/Leu (51%) genotypes in cancer cases and in controls (50% each) were found. The allelic frequencies of Pro and Leu were 74% versus 26% and 75% versus 25% in breast cancer cases and controls respectively. No association was observed in allele frequencies of Pro and Leu, and familial history. Only an overall association of GPX1 Pro198Leu with grade of cancer (Pro/Leu vs. Pro/Pro: p = .0200) was detected.ConclusionThe result of this study suggested that GPX1 Pro198Leu polymorphism could not be a risk factor for breast cancer in Rwanda. However, large‐scale studies on the effect of this polymorphism on the factors disturbing the redox homeostasis are needed for conclusive understanding.

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Section: Introductionmentioning

confidence: 99%

Association between glutathione peroxidase 1 codon 198 variant and the occurrence of breast cancer in Rwanda

Habyarimana

Bakri

Mugenzi

et al. 2018

Molec Gen & Gen Med

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“…Habyarimana reported that there was no difference between allele frequencies of Pro and Leu in breast cancer cases and controls, but they detected an overall association of GPX1 Pro198Leu (rs1050450) with grade of cancer . The results of a meta‐analysis performed by Men et al showed the significant correlation of the rs1050450 polymorphism with an increased risk of bladder cancer, while there was no significant association for prostate cancer . In addition, the meta‐analysis by Chen et al indicated the correlation of the individuals with variant Leu allele of rs1050450 with an increased cancer risk in dominant genetic model; however, Hong et al's meta‐analysis results showed no association of GPX1 gene rs1050450 polymorphism with cancer risk in any of dominant and recessive models .…”

Section: Discussionmentioning

confidence: 99%

“…29 The results of a meta-analysis performed by Men et al showed the significant correlation of the rs1050450 polymorphism with an increased risk of bladder cancer, while there was no significant association for prostate cancer. 30 In addition, the meta-analysis by Chen et al indicated the correlation of the individuals with variant Leu allele of rs1050450 with an increased cancer risk in dominant genetic model; however, Hong et al's metaanalysis results showed no association of GPX1 gene rs1050450 polymorphism with cancer risk in any of dominant and recessive models. 31 Recent study by Yang et al showed the effect of rs1050450 on breast cancer risk, 32 while Nikic et al and Zhang et al showed no significant association between rs1050450 polymorphism and metastatic urothelial bladder 33 and Gastric 34 cancers, respectively.…”

Section: Discussionmentioning

confidence: 99%

The effects of the genetic polymorphisms of antioxidant enzymes on susceptibility to papillary thyroid carcinoma

et al. 2020

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Several lines of evidences have indicated that inflammation play an important role in the carcinogenesis. During the inflammatory processes, free radical species are produced from oxidative stress. In normal conditions, enzymatic and nonenzymatic antioxidants remove these products. Manganese superoxide dismutase (MnSOD), glutathione peroxidase‐1 (GPx‐1), and catalase (CAT) are three important enzymes. Therefore, this study aimed to evaluate the effects of MnSOD (SOD2), GPX‐1, and CAT genetic polymorphisms on papillary thyroid carcinoma (PTC) susceptibility. A total of 134 patients with PTC and 151 healthy controls were recruited to participate in this study. All samples were genotyped for SOD2 rs4880, GPX1 1050450, and CAT rs7943316 polymorphisms by polymerase chain reaction‐restriction fragment length polymorphism method. The frequencies of the rs1050450, rs4880, and rs7943316 alleles and genotypes were not different between PTC patients and controls. However, the TC genotype of SOD2 rs4880 polymorphism was significantly higher in males compared to that in females in PTC patients (odds ratio [OR], 3.9 [95% CI, 1.5–11], p = .007). The rs4880 polymorphism was also associated with higher stages (III‐IV) of PTC in dominant model. No significant correlation was found between GPX1‐rs1050450 and CAT‐rs7943316 polymorphisms and demographic, clinical, and pathological features of the disease. The SOD2 rs4880CT genotype was more frequent in males with PTC and patients with higher stages (III–IV) of disease (OR, 2.9 [95% CI, 1.1–7.7], p = .04). However, no significant association was found between GPX1‐rs1050450 and CAT‐rs7943316 variants and PTC or its demographic, clinical, and pathological features.

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“…This polymorphism has not been represented on previous GWAS products, and was only recently genotyped in the HapMap or in the 1000 Genomes project, so it is possible that this putative association was not detectable in prior GWAS, and inconsistent results were found for this association in candidate analyses. Although some studies observed a trend towards an inverse association between rs1050450 and prostate cancer for carriers of alternative allele of rs1050450 [28], others found an absence of association [33, 29, 34] or in an increase in risk for carriers of alternative alleles [32]. Our study is the first that shows an inverse association with a p < 0.05, but also the first having statistical power to detect a weak association, and the results of the meta-analysis reinforced our observations.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium

Blein

Berndt

Joshi

et al. 2014

Free Radical Research

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Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione peroxidase (GPX-1; rs1050450 Pro198Leu) are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risk and survival with these variants, and interactions between rs4880 - rs1050450 and alcohol consumption - rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98 respectively) or prostate cancer (p-interaction of 0.49 and 0.50 respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79 – 0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49 – 0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation.

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The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis

Cited by 24 publications

References 29 publications

Association between glutathione peroxidase 1 codon 198 variant and the occurrence of breast cancer in Rwanda

Association between glutathione peroxidase 1 codon 198 variant and the occurrence of breast cancer in Rwanda

The effects of the genetic polymorphisms of antioxidant enzymes on susceptibility to papillary thyroid carcinoma

Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium

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