Genetic polymorphism of manganese superoxide dismutase (MnSOD) and breast cancer susceptibility (original) (raw)

Abstract

Within mitochondria, manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species (ROS). An alanine-9valine (Ala-9Val) polymorphism in the mitochondrial targeting sequence of MnSOD has been described and has recently been associated with risk of human breast cancer. Our present case-control study was performed to explore the association between MnSOD genetic polymorphism and individual susceptibility to breast cancer. Ala-9Val polymorphism in the signal sequence of the protein for MnSOD was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a study population. There was no significant difference in risk for breast cancer development between patients positive and negative for the MnSOD Ala allele with adjusted odds ratio (OR): 0.86 (95% confidence interval (CI) 0.43 to 1.72). When MnSOD Ala was combined with either cytochrome P450 1B1 CYP1B1*1 and catechol O-methyltransferase COMT-L (V158M) genotypes, the risk for developing breast cancer was significantly increased in patients with a body mass index (BMI) greater than 24 kg m À2 (OR: 1.42 (95%CI ¼ 1.04-1.93)).

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.

References (11)

  1. Kocabas ¸NA. Genetic polymorphisms in steroid hormone meta- bolizing enzymes in human breast cancer. Turkish J Med Sci 2002; 32: 217-221.
  2. Table 1. MnSOD allele frequencies and susceptibility of breast cancer by different variables 2. Emerit I. Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis. Free Rad Biol Med 1994; 16: 99-109.
  3. Halliwell B. Free radicals, antioxidants, and human diseases, curiosity, cause or consequence? Lancet 1994; 344: 721- 724.
  4. Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of CuZn-SOD, Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Rad Biol Med 2002; 33: 337-349.
  5. Soini Y, Vakkala M, Kahlos K, Paakko P, Kinnula V. MnSOD expression is less frequent in tumour cells of invasive breast carcinomas than in in situ carcinomas or non-neoplastic breast epithelial cells. J Pathol 2001; 195: 156-162.
  6. Li Z, Khaletskiy A, Wang J, Wong JYC, Oberley LW, Li JJ. Genes regulated in human breast cancer cells overexpressing MnSOD. Free Rad Biol Med 2001; 30: 260-267.
  7. Shimoda-Matsubayashi S, Matsumine H, Kobayashi T, Nakagawa-Hattori Y, Shimizu Y, Mizuno Y. Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. Biochem Bio- phys Res Commun 1996; 226: 561-565.
  8. Daly AK, Steen VM, Fairbrother KS, Idle JR. CYP2D6 multi- allelism. Methods Enzymol 1996; 272: 199-210.
  9. Ambrosone CB, Freudenheim JL, Thompson PA, et al. MnSOD genetic polymorphisms, dietary antioxidants, and risk of breast cancer. Cancer Res 1999; 59: 602-606.
  10. Mitrunen K, Sillanpaa P, Kataja V, et al. Association between MnSOD gene polymorphism and breast cancer risk. Carcino- genesis 2001; 22: 827-829.
  11. Kocabas ¸NA, S ¸ardas ¸S, Cholerton S, Daly AK, Karakaya AE. Cytochorome P450 CYP1B1 and Catechol O-methyltransferase (COMT) genetic polymorphisms and breast cancer susceptibil- ity in a Turkish population. Arch Toxicol 2002; 76: 643-649.