Target Sequence Polymorphism of Human Manganese Superoxide Dismutase Gene and Its Association with Cancer Risk: A Review

Bag, Arundhati; Bag, Niladri

doi:10.1158/1055-9965.epi-08-0235

Cited by 91 publications

(65 citation statements)

References 49 publications

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“…The 47cytosine-to-thymine (47C!T) transition at codon 16 in the SOD2 gene (reference SNP 4880 [rs4880]) creates a sense mutation of alanine (Ala)-tovaline (Val) in the SOD2 protein, which affects protein folding and localization. 6 Miscoding of Ala to Val in SOD2 will result in SOD2 arresting in the inner mitochondrial membrane but not in the mitochondrial matrix, therefore reducing its functional activities. 6 Carriage of 1 or 2 Ala-SOD2 allele(s) reportedly has been associated with greater risks of hepatocellular carcinoma, 7 gastric cancer, 8 prostate cancer 9 and a poor prognosis in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

“…6 Miscoding of Ala to Val in SOD2 will result in SOD2 arresting in the inner mitochondrial membrane but not in the mitochondrial matrix, therefore reducing its functional activities. 6 Carriage of 1 or 2 Ala-SOD2 allele(s) reportedly has been associated with greater risks of hepatocellular carcinoma, 7 gastric cancer, 8 prostate cancer 9 and a poor prognosis in breast cancer. 10 The SNP in the GSTP1 gene (rs1695) is a substitution of A (isoleucine [Iso]) to G (valine [Val]) at position 105 that results in miscoded GSTP1 protein with decreased enzymatic activity and less effective detoxification.…”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer

Zhu

Luk

et al. 2012

Cancer

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BACKGROUND: Excessive reactive oxygen species (ROS) accumulation is a common phenomenon in carcinogenesis. However, the rationale behind ROS involvement in gastric cancer is unclear. In this study, the authors investigated the clinical significance of the single nucleotide polymorphisms (SNPs) of 2 ROS metabolic process-related genes: superoxide dismutase 2 (SOD2) and glutathione Stransferase p (GSTP1). METHODS: In total of 929 patients with gastric cancer who had definitive clinicopathologic and follow-up data were collected. SOD2 reference SNP 4880 (rs4880) and GSTP1 rs1695 genotyping were examined in DNA samples extracted from paraffin-embedded tumor tissue. Association of the 2 SNPs with each clinicopathologic feature was analyzed using the Pearson chisquare test and the independent Student t test. Gastric cancer-specific overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Multivariate Cox regression analyses of these SNPs also were performed. RESULTS: The SOD2 rs4880 CT þ CC genotypes were significantly associated with a high level of lymph node metastasis (P ¼ .023), whereas the GSTP1 rs1695 GA þ GG genotypes were significantly associated with larger tumor size (>5 cm long; P ¼ .048). Kaplan-Meier and Cox regression data indicated that the SOD2 rs4880 CT þ CC genotypes alone (hazard ratio, 1.299; 95% confidence interval, 1.053-1.603; P ¼ .015) and the GSTP1 rs1695 GA þ GG combined genotypes (hazard ratio, 1.496; 95% CI, 1.078-2.074; P ¼ .016) were independent predictors for overall survival. CONCLUSIONS: The current data, based on a large cohort (n ¼ 929) of Chinese patients with gastric cancer, suggested that the presence of SOD2 rs4880 and GSTP1 rs1695 genotypes may contribute to cancer progression as well as tumor aggressiveness. The components of ROS metabolism pathways may be potential therapeutic targets for this aggressive malignancy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer

Zhu

Luk

et al. 2012

Cancer

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“…Although the mechanisms underlying these associations are uncertain, chronic inflammation is known to induce oxidant-generating enzymes and the subsequent production of reactive oxygen and nitrogen species (ROS and RNS) [9]. Furthermore, endogenous antioxidant enzymes, such as, manganese superoxide dismutase (MnSOD), and antioxidants, such as, carotenoids and tocopherols are known to play significantly roles in cellular defense against oxidative stress [10].…”

Section: Introductionmentioning

confidence: 99%

Functional polymorphism in manganese superoxide dismutase and antioxidant status: Their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer

Tong

Lee

Song

et al. 2009

Gynecologic Oncology

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“…Previously, it has been reported that the cytosolic stress-inducible hsp70, a molecular chaperone, associates with SOD2 after synthesis and that the chaperone maintains the enzyme in an import-competent, unfolded conformation in an ATP-dependent manner (3)(4)(5)(6)(7)(8). Mice homozygous for hsp70 gene disruption exhibit a marked reduction in SOD2 activity, providing in vivo evidence for the role of hsp70 in regulating SOD2 (9).…”

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confidence: 99%

Domain Mapping of Heat Shock Protein 70 Reveals That Glutamic Acid 446 and Arginine 447 Are Critical for Regulating Superoxide Dismutase 2 Function

Afolayan

Alexander

Holme

et al. 2017

Journal of Biological Chemistry

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Edited by Linda SpremulliStress-inducible heat shock protein 70 (hsp70) interacts with superoxide dismutase 2 (SOD2) in the cytosol after synthesis to transfer the enzyme to the mitochondria for subsequent activation. However, the structural basis for this interaction remains to be defined. To map the SOD2-binding site in hsp70, mutants of hsp70 were made and tested for their ability to bind SOD2. These studies showed that SOD2 binds in the amino acid 393-537 region of the chaperone. To map the hsp70-binding site in SOD2, we used a series of pulldown assays and showed that hsp70 binds to the amino-terminal domain of SOD2. To better define the binding site, we used a series of decoy peptides derived from the primary amino acid sequence in the SOD2-binding site in hsp70. This study shows that SOD2 specifically binds to hsp70 at 445 GERAMT 450 . Small peptides containing GERAMT inhibited the transfer of SOD2 to the mitochondria and decreased SOD2 activity in vitro and in vivo. To determine the amino acid residues in hsp70 that are critical for SOD2 interactions, we substituted each amino acid residue for alanine or more conservative residues, glutamine or asparagine, in the GERAMT-binding site. Substitutions of E446A/Q and R447A/Q inhibited the ability of the GERAMT peptide to bind SOD2 and preserved SOD2 function more than other substitutions. Together, these findings indicate that the GERAMT sequence is critical for hsp70-mediated regulation of SOD2 and that Glu 446 and Arg 447 cooperate with other amino acid residues in the GERAMT-binding site for proper chaperone-dependent regulation of SOD2 antioxidant function.

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Target Sequence Polymorphism of Human Manganese Superoxide Dismutase Gene and Its Association with Cancer Risk: A Review

Abstract: In normal state of a cell, endogenous antioxidant enzyme system maintains the level of reactive oxygen species generated by mitochondrial respiratory chain.

Cited by 91 publications

References 49 publications

Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer

Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer

Functional polymorphism in manganese superoxide dismutase and antioxidant status: Their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer

Domain Mapping of Heat Shock Protein 70 Reveals That Glutamic Acid 446 and Arginine 447 Are Critical for Regulating Superoxide Dismutase 2 Function

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