Skip to main content

Advertisement

SpringerLink
Log in

Polymorphism in the manganese superoxide dismutase (MnSOD) gene and risk of breast cancer in young women

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose: Manganese superoxide dismutase (MnSOD) is one of the major enzymes implicated in the cellular defence against reactive oxygen species. Low expression of MnSOD has been observed in different cancer tissues and several reports have shown that overexpression of MnSOD inhibits growth in various human cancer cells. These observations suggest that MnSOD is involved in carcinogenesis. A polymorphism (Ala-9Val) in the mitochondrial targeting sequence (MTS) of the MnSOD gene has been proposed to affect protein localization and thereby influence cellular defence against superoxide radicals. Methods: In the present case-control study, including 118 early onset breast cancer patients (≤36 years) and 174 age-matched controls, the MTS polymorphism and loss of heterozygosity (LOH) in the locus of MnSOD were analysed. Results: We found that individuals with MnSODVal/Val and MnSODVal/Ala genotypes showed an increased risk of breast cancer (OR, 2.7; 95% CI, 2.2–5.5, p=0.01, OR, 3.0; 95%CI, 1.4–6.5, p=0.002). Moreover, 45% of the informative cases expressed allelic loss at the chromosomal locus of the MnSOD gene. No correlation was found between LOH and the genotype. Conclusion: The present study suggests that MnSOD may be implicated in breast carcinogenesis in young women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Allen AG, Tresini M (2000) Oxidative stress and gene regulation. Free Radic Biol Med 28:463–499

    Article  CAS  PubMed  Google Scholar 

  • Ambrosone CB, Freudenheim JL, Thompson PA, Bowman E, Vena JE, Marshall JR, Graham S, Laughlin R, Nemoto T, Shields PG (1999) Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer. Cancer Res 59:602–606

    CAS  PubMed  Google Scholar 

  • Bergman-Jungeström M, Gentile M, Lundin A-C, The South-East Breast Cancer Group, Wingren S (1999) Association between CYP17 gene polymorphism and risk of breast cancer in young women. Int J Cancer (Pred Oncol) 84:350–353

    Google Scholar 

  • Bernstein L (2002) Epidemiology of endocrine-related risk factors for breast cancer. J Mammary Gland Biol Neoplasia 7:3–15

    Article  PubMed  Google Scholar 

  • Cerutti PA (1994) Oxy-radicals and cancer. Lancet 344:862–863

    Article  CAS  PubMed  Google Scholar 

  • Chappell SA, Walsh T, Walker RA, Shaw JA (1997) Loss of heterozygosity at chromosome 6q in preinvasive and early invasive breast carcinomas. Br J Cancer 75(9):1324–1329

    CAS  PubMed  Google Scholar 

  • Chou PY, Fasman GD (1979) Prediction of beta-turns. Biophys J 26:367–373

    CAS  PubMed  Google Scholar 

  • Church SL, Grant JW, Meese EU, Trent JM (1992) Sublocalization of the gene encoding manganese superoxide dismutase (MnSOD/SOD2) to 6q25 by fluorescence in situ hybridization and somatic cell hybrid mapping. Genomics 14(3):823–825

    CAS  PubMed  Google Scholar 

  • Church SL, Grant JW, Ridnour LA, Oberley LW, Swanson PE, Meltzer PS, Trent JM (1993) Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells. Proc Natl Acad Sci USA 1:3113–3117

    Google Scholar 

  • Collaborative Group on Hormonal Factors in Breast Cancer (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58.209 women with breast cancer and 101.986 women without the disease. Lancet 358:1389–1399

    Google Scholar 

  • Cooke IE, Shelling AN, Le Meuth VG, Charnock ML, Ganesan TS (1996) Allele loss on chromosome arm 6q and fine mapping of the region at 6q27 in epithelial ovarian cancer. Genes Chromosomes Cancer 15:223–233

    Article  CAS  PubMed  Google Scholar 

  • Dreher D, Junod AF (1996) Role of oxygen free radicals in cancer development. Eur J Cancer 32:30–38

    Article  Google Scholar 

  • Fujii H, Zhou W, Gabrielson E (1996) Detection of frequent allelic loss of 6q23-6q25.2 in microdissected human breast cancer tissues. Genes Chromosomes Cancer 16(1):35–39

    Article  CAS  PubMed  Google Scholar 

  • Hiroi S, Harada H, Nishi H, Satoh M, Nagai R, Kimura A (1999) Polymorphism in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy (in Japanese). Biochem Biophys Res Commun 261:332–339

    Article  CAS  PubMed  Google Scholar 

  • Hung R, Boffetta P, Brennan P, Malaveille C, Gelatti U, Placidi D, Carta A, Hautefeuille A, Porru S (2004) Genetic polymorphism of MPO, COMT, MnSOD, NQ01, interactions with environmental exposures and bladder cancer. Carcinogenesis 25:973–978

    Article  CAS  PubMed  Google Scholar 

  • van Landeghem GF, Tabatabaie P, Kucinskas V, Saha N (1999) Ethnic variation in the mitochondrial targeting sequence polymorphism of MnSOD. Hum Hered 49:190–193

    Article  PubMed  Google Scholar 

  • Li N, Oberley TD, Oberley LW, Zhong W (1998) Overexpression of manganese superoxide dismutase in DU145 human prostate carcinoma cells has multiple effects on cell phenotype. Prostate 35:221–233

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Oberley LW, Oberley TD (1997) Transfection and expression of MnSOD cDNA decreases tumor malignancy of human oral squamous carcinoma SCC-25 cells. Hum Gene Ther 20(8):585–595

    Google Scholar 

  • Miki Y, Swense J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J et al. (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71

    CAS  PubMed  Google Scholar 

  • Millikan R, Player J, De Cotret A, Moorman P, Pittman G, Vannappagari V, Tse C, Keku T (2004) Manganese superoxide dismutase Ala-9Val polymorphism and risk of breast cancer in a population-based case control study of African Americans and whites. Breast Cancer Res 6:264–274

    Article  Google Scholar 

  • Mitrunen K, Sillanpaa P, Kataja V, Eskelinen M, Kosma VM, Benhamou S, Uusitupa M, Hirvonen A (2001) Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk. Carcinogenesis 22:827–829

    Article  CAS  PubMed  Google Scholar 

  • Oberley LW (2001) Anticancer therapy by overexpression of superoxide dismutase. Antioxid Redox Signal 3:461–472

    Article  CAS  PubMed  Google Scholar 

  • Oberley LW, St Clair DK, Ridnour LA, Oberley TD (1995) Phenotypic changes induced in human breast cancer cells by overexpression of manganese-containing superoxide dismutase. Oncogene 18:1989–2000

    Google Scholar 

  • Ohshima K, Haraokaa S, Ishihara S, Ohgami A, Yoshioka S, Suzumiya J, Kikuchi M (2002) Analysis of chromosome 6q deletion in EBV-associated NK cell leukaemia/lymphoma. Leuk Lymphoma 43:293–300

    Article  CAS  PubMed  Google Scholar 

  • Olson SH, Carlson MDA, Ostrer H, Harlap S, Stone A, Winters M, Ambrosone CB (2004) Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer. Gynecol Oncol 93:615–620

    Article  CAS  PubMed  Google Scholar 

  • Schiffer M, Edmundson AB (1967) Use of helical wheels to represent the structures of proteins and to identify segments with helical potential. Biophys J 7:121–135

    CAS  PubMed  Google Scholar 

  • Shimoda-Matsubayashi S, Matsumine H, Kobayashi T, Nakagawa-Hattori Y, Shimizu Y, Mizuno Y (1996) Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson’s disease. Biochem Biophys Res Commun 13:561–565

    Article  Google Scholar 

  • Tamimi RM, Hankinson S, Spiegelman D, Coliditz G, Hunter D (2004) Manganese superoxide polymorphism, plasma antioxidants, cigarette smoking, and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 13:989–996

    CAS  PubMed  Google Scholar 

  • Wang L, Miller P, Sai Y, Liu G, Su L, Wain J, Lynch T, Christiani D (2001a) Manganese superoxide dismutase alanine-to-valine polymorphism at codon 16 and lung cancer risk. J Natl Cancer Inst 93:1818–1821

    Article  CAS  PubMed  Google Scholar 

  • Wang VW, Bell DA, Berkowitz RS, Mok SC (2001b) Whole genome amplification and high-throughput allelotyping identified five distinct deletion regions on chromosomes 5 and 6 in microdissected early-stage ovarian tumors. Cancer Res 61:4169–4174

    CAS  PubMed  Google Scholar 

  • Woodson K, Tangrea J, Lehman T, Modali R, Taylor K, Snyder K, Taylor P, Virtamo J, Albanes D (2003) Manganese superoxide dismutase (MnSOD) polymorphism, α-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland). Cancer Causes Control 14:513–518

    Article  PubMed  Google Scholar 

  • Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collin Gregory S, Gumbs C, Micklem G, Barfoot R, Hamoudi R et al. (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792

    Article  CAS  PubMed  Google Scholar 

  • Yan T, Oberley LW, Zhong W, St Clair DK (1996) Manganese-containing superoxide dismutase overexpression causes phenotypic reversion in SV40-transformed human lung fibroblasts. Cancer Res 56:2864–2871

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Swedish Cancer and Allergy Society, the Regional Cancer Society of Ötergöland, the research funds at the University Hospital of Linköping, Lions Research Foundation, and the Research Council in southeast Sweden.

Author information

Authors and Affiliations

  1. Department of Biomedicine and Surgery, Division of Cell biology, Faculty of Health Sciences, University Hospital, 581 85, Linköping, Sweden

    Malin Bergman, Pia Palmebäck Wegman & Sten Wingren

  2. Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, University Hospital, 581 85, Linköping, Sweden

    Marie Ahnström

Authors
  1. Malin Bergman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie Ahnström
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pia Palmebäck Wegman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sten Wingren
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sten Wingren.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bergman, M., Ahnström, M., Palmebäck Wegman, P. et al. Polymorphism in the manganese superoxide dismutase (MnSOD) gene and risk of breast cancer in young women. J Cancer Res Clin Oncol 131, 439–444 (2005). https://doi.org/10.1007/s00432-004-0663-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-004-0663-7

Keywords

Search

Navigation