Abstract
Breast cancer is the most common cancer in women worldwide, but its etiology is still unclear. It is believed that oxidative stress plays an essential role in the development of breast cancer, while SOD2 is one of the primary enzymes that directly convert potential harmful oxidizing species to harmless metabolites. The association of SOD2 Val16Ala polymorphism and breast cancer risk has been widely reported, but results of previous studies were somewhat contradictory and underpowered. To overcome the limitations of individual study and to understand the real situation, we conducted a systematic review and meta-analysis toward the association between SOD2 Val16Ala polymorphism and breast cancer. Through retrieving MEDLINE, PubMed, Embase, and Web of Science, a total of 17 studies with 9,710 cases and 11,041 controls were identified. The results showed that no significant associations were found for the allele contrast (allele Ala vs. allele Val: OR = 1.020, 95% CI = 0.979–1.062), additive genetic model (Ala/Ala vs. Val/Val: OR = 1.091, 95% CI = 0.969–1.229), dominant genetic model (Ala/Ala +Ala/Val vs. Val/Val: OR = 1.045, 95% CI = 0.961–1.136), and recessive genetic model (Ala/Ala vs. Val/Val +Ala/Val: OR = 1.027, 95% CI = 0.956–1.102). In the stratified analysis by ethnicity and menopausal status, significant associations were also not detected in all genetic models. Conclusively, this meta-analysis strongly suggests that SOD2 Val16Ala polymorphism is not associated with breast cancer susceptibility.
Similar content being viewed by others
References
Koksoy C, Kavas GO, Akcil E, Kocaturk PA, Kara S, Ozarslan C (1997) Trace elements and superoxide dismutase in benign and malignant breast diseases. Breast Cancer Res Treat 45:1–6
DiSilvestro RA, Goodman J, Dy E, Lavalle G (2005) Soy isoflavone supplementation elevates erythrocyte superoxide dismutase, but not plasma ceruloplasmin in postmenopausal breast cancer survivors. Breast Cancer Res Treat 89:251–255. doi:10.1007/s10549-004-2227-6
Emerit I (1994) Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis. Free Radic Biol Med 16:99–109
Feig DI, Reid TM, Loeb LA (1994) Reactive oxygen species in tumorigenesis. Cancer Res 54:1890s–1894s
Bica CG, de Moura da Silva LL, Toscani NV, da Cruz IB, Sa G, Graudenz MS, Zettler CG (2009) MnSOD gene polymorphism association with steroid-dependent cancer. Pathol Oncol Res 15:19–24. doi:10.1007/s12253-008-9064-6
Kattan Z, Minig V, Leroy P, Dauca M, Becuwe P (2008) Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells. Breast Cancer Res Treat 108:203–215. doi:10.1007/s10549-007-9597-5
Eras-Erdogan N, Akbas E, Senli H, Kul S, Colak T (2009) Relationship between polymorphism in the manganese superoxide dismutase gene and breast cancer. Mutat Res. doi:S1383-5718(09)00272-1[pii]10.1016/j.mrgentox.2009.08.006
Rosenblum JS, Gilula NB, Lerner RA (1996) On signal sequence polymorphisms and diseases of distribution. Proc Natl Acad Sci USA 93:4471–4473
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012. doi:jst00003[pii]
Little J, Bradley L, Bray MS, Clyne M, Dorman J, Ellsworth DL, Hanson J, Khoury M, Lau J, O’Brien TR, Rothman N, Stroup D, Taioli E, Thomas D, Vainio H, Wacholder S, Weinberg C (2002) Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. Am J Epidemiol 156:300–310
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114. doi:S1551-7144(06)00048-6[pii]10.1016/j.cct.2006.04.004
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188. doi:0197-2456(86)90046-2[pii]
Kostrykina NA, Pechkovskiy EA, Boyarskikh UA, Sushko AG, Voronina EN, Lazarev AF, Petrova VD, Zarubina NA, Selezneva IA, Sinkina TV, Terekhova SA, Filipenko ML (2009) Associations of polymorphic variant of MnSOD gene with breast cancer in residents of the Altai Region. Bull Exp Biol Med 147:84–87
Justenhoven C, Hamann U, Schubert F, Zapatka M, Pierl CB, Rabstein S, Selinski S, Mueller T, Ickstadt K, Gilbert M, Ko YD, Baisch C, Pesch B, Harth V, Bolt HM, Vollmert C, Illig T, Eils R, Dippon J, Brauch H (2008) Breast cancer: a candidate gene approach across the estrogen metabolic pathway. Breast Cancer Res Treat 108:137–149. doi:10.1007/s10549-007-9586-8
Slanger TE, Chang-Claude J, Wang-Gohrke S (2006) Manganese superoxide dismutase Ala-9Val polymorphism, environmental modifiers, and risk of breast cancer in a German population. Cancer Causes Control 17:1025–1031. doi:10.1007/s10552-006-0043-5
Silva SN, Cabral MN, Bezerra de Castro G, Pires M, Azevedo AP, Manita I, Pina JE, Rueff J, Gaspar J (2006) Breast cancer risk and polymorphisms in genes involved in metabolism of estrogens (CYP17, HSD17beta1, COMT and MnSOD): possible protective role of MnSOD gene polymorphism Val/Ala and Ala/Ala in women that never breast fed. Oncol Rep 16:781–788
Gaudet MM, Gammon MD, Santella RM, Britton JA, Teitelbaum SL, Eng SM, Terry MB, Bensen JT, Schroeder J, Olshan AF, Neugut AI, Ambrosone CB (2005) MnSOD Val-9Ala genotype, pro- and anti-oxidant environmental modifiers, and breast cancer among women on Long Island, New York. Cancer Causes Control 16:1225–1234. doi:10.1007/s10552-005-0375-6
Bergman M, Ahnstrom M, Palmeback Wegman P, Wingren S (2005) Polymorphism in the manganese superoxide dismutase (MnSOD) gene and risk of breast cancer in young women. J Cancer Res Clin Oncol 131:439–444. doi:10.1007/s00432-004-0663-7
Cheng TC, Chen ST, Huang CS, Fu YP, Yu JC, Cheng CW, Wu PE, Shen CY (2005) Breast cancer risk associated with genotype polymorphism of the catechol estrogen-metabolizing genes: a multigenic study on cancer susceptibility. Int J Cancer 113:345–353. doi:10.1002/ijc.20630
Tamimi RM, Hankinson SE, Spiegelman D, Colditz GA, Hunter DJ (2004) Manganese superoxide dismutase polymorphism, plasma antioxidants, cigarette smoking, and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 13:989–996. doi:13/6/989[pii]
Cai Q, Shu XO, Wen W, Cheng JR, Dai Q, Gao YT, Zheng W (2004) Genetic polymorphism in the manganese superoxide dismutase gene, antioxidant intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. Breast Cancer Res 6:R647–R655. doi:bcr929[pii]10.1186/bcr929
Millikan RC, Player J, de Cotret AR, Moorman P, Pittman G, Vannappagari V, Tse CK, 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:R264–R274. doi:10.1186/bcr786[pii]
Knight JA, Onay UV, Wells S, Li H, Shi EJ, Andrulis IL, Ozcelik H (2004) Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 13:146–149
Egan KM, Thompson PA, Titus-Ernstoff L, Moore JH, Ambrosone CB (2003) MnSOD polymorphism and breast cancer in a population-based case-control study. Cancer Lett 199:27–33. doi:S0304383503003495[pii]
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
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
Kocabas NA, Sardas S, Cholerton S, Daly AK, Elhan AH, Karakaya AE (2005) Genetic polymorphism of manganese superoxide dismutase (MnSOD) and breast cancer susceptibility. Cell Biochem Funct 23:73–76. doi:10.1002/cbf.1128
Ma XY, QI XW, Chen CH, Lin H, Xiong HY, Li YF, Jiang J (2009) Association between CYP19 polymorphisms and breast cancer risk: results from 10592 cases and 11720 controls. Breast Cancer Res Treat. doi:10.1007/s10549-009-0693-6
Zhang Z, Wang M, Wu D, Tong N, Tian Y (2009) P53 codon 72 polymorphism contributes to breast cancer risk: a meta-analysis based on 39 case-control studies. Breast Cancer Res Treat. doi:10.1007/s10549-009-0480-4
Wang Z, Fu Y, Tang C, Lu S, Chu WM (2009) SULT1A1 R213H polymorphism and breast cancer risk: a meta-analysis based on 8,454 cases and 11,800 controls. Breast Cancer Res Treat. doi:10.1007/s10549-009-0648-y
Chen P, Hu P, Xie D, Qin Y, Wang F, Wang H (2009) Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat. doi:10.1007/s10549-009-0593-9
Tang C, Chen N, Wu M, Yuan H, Du Y (2009) Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat 117:391–399. doi:10.1007/s10549-008-0262-4
Tao W, Wang C, Han R, Jiang H (2009) HER2 codon 655 polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 114:371–376. doi:10.1007/s10549-008-0010-9
Sergentanis TN, Economopoulos KP (2009) Association of two CASP8 polymorphisms with breast cancer risk: a meta-analysis. Breast Cancer Res Treat. doi:10.1007/s10549-009-0471-5
Qiu LX, Yuan H, Yu KD, Mao C, Chen B, Zhan P, Xue K, Zhang J, Hu XC (2009) Glutathione S-transferase M1 polymorphism and breast cancer susceptibility: a meta-analysis involving 46,281 subjects. Breast Cancer Res Treat. doi:10.1007/s10549-009-0636-2
Sergentanis TN, Economopoulos KP (2009) GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. doi:10.1007/s10549-009-0520-0
Acknowledgements
This work was not supported by any funds.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ma, X., Chen, C., Xiong, H. et al. No association between SOD2 Val16Ala polymorphism and breast cancer susceptibility: a meta-analysis based on 9,710 cases and 11,041 controls. Breast Cancer Res Treat 122, 509–514 (2010). https://doi.org/10.1007/s10549-009-0725-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-009-0725-2