Breast Cancer Research and Treatment

, Volume 121, Issue 3, pp 703–708 | Cite as

Glutathione S-transferase M1 polymorphism and breast cancer susceptibility: a meta-analysis involving 46,281 subjects

  • Li-Xin Qiu
  • Hui Yuan
  • Ke-Da Yu
  • Chen Mao
  • Bo Chen
  • Ping Zhan
  • Kai Xue
  • Jian Zhang
  • Xi-Chun Hu
Epidemiology

Abstract

Published data on the association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the GSTM1 present/null polymorphism and breast cancer risk. The pooled ORs were performed for null versus present genotype. A total of 59 studies including 20,993 cases and 25,288 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with null genotype when all studies were pooled into the meta-analysis (OR = 1.10, 95% CI = 1.04–1.16). In the subgroup analysis by ethnicity, significantly increased risks were found for Caucasians (OR = 1.05, 95% CI = 1.00–1.10) and Asians (OR = 1.21, 95% CI = 1.08–1.35). When stratified by population-based studies or hospital-based studies, statistically significantly elevated risks were found among population-based studies (OR = 1.11, 95% CI = 1.03–1.20). In the subgroup analysis by menopausal status, statistically significantly increased risks were found among postmenopausal women (OR = 1.15, 95% CI = 1.04–1.28). In conclusion, this meta-analysis suggests that the GSTM1 null genotype is a low-penetrant risk factor for developing breast cancer.

Keywords

GSTM1 Polymorphism Breast cancer Susceptibility Meta-analysis 

References

  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics 2002. CA Cancer J Clin 55:74–108CrossRefPubMedGoogle Scholar
  2. 2.
    Lichtenstein P, Holm NV, Verkasalo PK (2000) Environmental and heritable factors in the causation of cancer. N Engl J Med 343:78–85CrossRefPubMedGoogle Scholar
  3. 3.
    Yager JD, Davidson NE (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med 354:270–282CrossRefPubMedGoogle Scholar
  4. 4.
    Yu KD, Di GH, Fan L, Wu J, Hu Z, Shen ZZ, Huang W, Shao ZM (2009) A functional polymorphism in the promoter region of GSTM1 implies a complex role for GSTM1 in breast cancer. FASEB J 23:2274–2287CrossRefPubMedGoogle Scholar
  5. 5.
    Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14:1821–1824CrossRefPubMedGoogle Scholar
  6. 6.
    Kelsey KT, Hankinson SE, Colditz GA, Springer K, Garcia-Closas M, Spiegelman D, Manson JE, Garland M, Stampfer MJ, Willett WC, Speizer FE, Hunter DJ (1997) Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases. Cancer Epidemiol Biomarkers Prev 6:511–515PubMedGoogle Scholar
  7. 7.
    Ambrosone CB, Coles BF, Freudenheim JL, Shields PG (1999) Glutathione-S-transferase (GSTM1) genetic polymorphisms do not affect human breast cancer risk, regardless of dietary antioxidants. J Nutr 129:565S–568SPubMedGoogle Scholar
  8. 8.
    Charrier J, Maugard CM, Le Mevel B, Bignon YJ (1999) Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility. Br J Cancer 79:346–353CrossRefPubMedGoogle Scholar
  9. 9.
    Garcia-Closas M, Kelsey KT, Hankinson SE, Spiegelman D, Springer K, Willett WC, Speizer FE, Hunter DJ (1999) Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility. J Natl Cancer Inst 91:1960–1964CrossRefPubMedGoogle Scholar
  10. 10.
    Helzlsouer KJ, Selmin O, Huang HY, Strickland PT, Hoffman S, Alberg AJ, Watson M, Comstock GW, Bell D (1998) Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J Natl Cancer Inst 90:512–518CrossRefPubMedGoogle Scholar
  11. 11.
    Curran JE, Weinstein SR, Griffiths LR (2000) Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility. Cancer Lett 153:113–120CrossRefPubMedGoogle Scholar
  12. 12.
    Millikan R, Pittman G, Tse CK, Savitz DA, Newman B, Bell D (2000) Glutathione S-transferases M1, T1, and P1 and breast cancer. Cancer Epidemiol Biomarkers Prev 9:567–573PubMedGoogle Scholar
  13. 13.
    Rundle A, Tang D, Zhou J, Cho S, Perera F (2000) The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue. Cancer Epidemiol Biomarkers Prev 9:1079–1085PubMedGoogle Scholar
  14. 14.
    Gudmundsdottir K, Tryggvadottir L, Eyfjord JE (2001) GSTM1, GSTT1, and GSTP1 genotypes in relation to breast cancer risk and frequency of mutations in the p53 gene. Cancer Epidemiol Biomarkers Prev 10:1169–1173PubMedGoogle Scholar
  15. 15.
    Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C, Lacroix A, Labuda D, Sinnett D (2001) Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions. Int J Cancer 92:220–225CrossRefPubMedGoogle Scholar
  16. 16.
    Mitrunen K, Jourenkova N, Kataja V, Eskelinen M, Kosma VM, Benhamou S, Vainio H, Uusitupa M, Hirvonen A (2001) Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. Cancer Epidemiol Biomarkers Prev 10:229–236PubMedGoogle Scholar
  17. 17.
    Xiong P, Bondy ML, Li D, Shen H, Wang LE, Singletary SE, Spitz MR, Wei Q (2001) Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study. Cancer Res 61:8465–8469PubMedGoogle Scholar
  18. 18.
    Dialyna IA, Arvanitis DA, Spandidos DA (2001) Genetic polymorphisms and transcriptional pattern analysis of CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes in breast cancer. Int J Mol Med 8:79–87PubMedGoogle Scholar
  19. 19.
    de Amorim L, Rossini A, Mendonca G, Lotsch P, de Almeida Simao T, de Moura Gallo C, Pinto L (2002) CYP1A1, GSTM1, and GSTT1 polymorphisms and breast cancer risk in Brazilian women. Cancer Lett 181:179–186CrossRefGoogle Scholar
  20. 20.
    Siegelmann-Danieli N, Buetow KH (2002) Significance of genetic variation at the glutathione S-transferase M1 and NAD(P)H:quinone oxidoreductase 1 detoxification genes in breast cancer development. Oncology 62:39–45CrossRefPubMedGoogle Scholar
  21. 21.
    Wu FY, Lee YJ, Chen DR, Kuo HW (2002) Association of DNA-protein crosslinks and breast cancer. Mutat Res 501:69–78PubMedGoogle Scholar
  22. 22.
    Zheng T, Holford TR, Zahm SH, Owens PH, Boyle P, Zhang Y, Wise JP Sr, Stephenson LP, Ali-Osman F (2002) Cigarette smoking, glutathione-s-transferase M1 and t1 genetic polymorphisms, and breast cancer risk (United States). Cancer Causes Control 13:637–645CrossRefPubMedGoogle Scholar
  23. 23.
    Zheng W, Wen WQ, Gustafson DR, Gross M, Cerhan JR, Folsom AR (2002) GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk. Breast Cancer Res Treat 74:9–16CrossRefPubMedGoogle Scholar
  24. 24.
    Matheson MC, Stevenson T, Akbarzadeh S, Propert DN (2002) GSTT1 null genotype increases risk of premenopausal breast cancer. Cancer Lett 181:73–79CrossRefPubMedGoogle Scholar
  25. 25.
    Li D, Walcott FL, Chang P (2002) Genetic and environmental determinants on tissue response to in vitro carcinogen exposure and risk of breast cancer. Cancer Res 62:4566–4570PubMedGoogle Scholar
  26. 26.
    Khedhaier A, Remadi S, Corbex M (2003) Glutathione S-transferases (GSTT1 and GSTM1) gene deletions in Tunisians: susceptibility and prognostic implications in breast carcinoma. Br J Cancer 89:1502–1507CrossRefPubMedGoogle Scholar
  27. 27.
    Zhu J, Chang P, Bondy ML, Sahin AA, Singletary SE, Takahashi S, Shirai T, Li D (2003) Detection of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 12:830–837PubMedGoogle Scholar
  28. 28.
    Egan KM, Cai Q, Shu XO, Jin F, Zhu TL, Dai Q, Gao YT, Zheng W (2004) Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis. Cancer Epidemiol Biomarkers Prev 13:197–204CrossRefPubMedGoogle Scholar
  29. 29.
    McCarty KM, Santella RM, Steck SE, Cleveland RJ, Ahn J, Ambrosone CB, North K, Sagiv SK, Eng SM, Teitelbaum SL, Neugut AI, Gammon MD (2009) PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk. Environ Health Perspect 117:552–558PubMedGoogle Scholar
  30. 30.
    Medeiros R, Soares R, Vasconcelos A, Schmitt F, Lopes C (2004) Glutathione S-transferase genotype GSTM1 as a predictor of elevated angiogenic phenotype in patients with early onset breast cancer. Angiogenesis 7:53–58CrossRefPubMedGoogle Scholar
  31. 31.
    Park SK, Yim DS, Yoon KS (2004) Combined effect of GSTM1, GSTT1, and COMT genotypes in individual breast cancer risk. Breast Cancer Res Treat 88:55–62CrossRefPubMedGoogle Scholar
  32. 32.
    Sarmanova J, Susova S, Gut I, Mrhalova M, Kodet R, Adamek J, Roth Z, Soucek P (2004) Breast cancer: role of polymorphisms in biotransformation enzymes. Eur J Hum Genet 12:848–854CrossRefPubMedGoogle Scholar
  33. 33.
    van der Hel OL, Peeters PH, Hein DW (2004) GSTM1 null genotype, red meat consumption and breast cancer risk (The Netherlands). Cancer Causes Control 15:295–303CrossRefPubMedGoogle Scholar
  34. 34.
    Gago-Dominguez M, Castelao JE, Sun CL, Van Den Berg D, Koh WP, Lee HP, Yu MC (2004) Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore. Carcinogenesis 25:2143–2147CrossRefPubMedGoogle Scholar
  35. 35.
    Roodi N, Dupont WD, Moore JH, Parl FF (2004) Association of homozygous wild-type glutathione S-transferase M1 genotype with increased breast cancer risk. Cancer Res 64:1233–1236CrossRefPubMedGoogle Scholar
  36. 36.
    Ceschi M, Sun CL, Van Den Berg D, Koh WP, Yu MC, Probst-Hensch N (2005) The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore. Carcinogenesis 26:1457–1464CrossRefPubMedGoogle Scholar
  37. 37.
    Chacko P, Joseph T, Mathew BS, Rajan B, Pillai MR (2005) Role of xenobiotic metabolizing gene polymorphisms in breast cancer susceptibility and treatment outcome. Mutat Res 581:153–163PubMedGoogle Scholar
  38. 38.
    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 113:345–353CrossRefPubMedGoogle Scholar
  39. 39.
    Linhares JJ, Da Silva ID, De Souza NC, Noronha EC, Ferraro O, De Carvalho CV, Baracat EC, Baracat FF (2005) Genetic polymorphism of GSTM1 in women with breast cancer and interact with reproductive history and several clinical pathologies. Biol Res 38:273–281CrossRefPubMedGoogle Scholar
  40. 40.
    Van der Hel OL, Bueno-de-Mesquita HB, van Gils CH, Roest M, Slothouber B, Grobbee DE, Peeters PH (2005) Cumulative genetic defects in carcinogen metabolism may increase breast cancer risk (The Netherlands). Cancer Causes Control 16:675–681CrossRefPubMedGoogle Scholar
  41. 41.
    Chang TW, Wang SM, Guo YL, Tsai PC, Huang CJ, Huang W (2006) Glutathione S-transferase polymorphisms associated with risk of breast cancer in southern Taiwan. Breast 15:754–761CrossRefPubMedGoogle Scholar
  42. 42.
    Wu SH, Tsai SM, Hou MF, Lin HS, Hou LA, Ma H, Lin JT, Yeh FL, Tsai LY (2006) Interaction of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferase M1 to breast cancer in Taiwanese woman without smoking and drinking habits. Breast Cancer Res Treat 100:93–98CrossRefPubMedGoogle Scholar
  43. 43.
    Edvardsen H, Kristensen VN, Grenaker Alnaes GI, Bohn M, Erikstein B, Helland A, Borresen-Dale AL, Fossa SD (2007) Germline glutathione S-transferase variants in breast cancer: relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy. Int J Radiat Oncol Biol Phys 67:1163–1171PubMedGoogle Scholar
  44. 44.
    Nordgard SH, Ritchie MD, Jensrud SD, Motsinger AA, Alnaes GI, Lemmon G, Berg M, Geisler S, Moore JH, Lonning PE, Borresen-Dale AL, Kristensen VN (2007) ABCB1 and GST polymorphisms associated with TP53 status in breast cancer. Pharmacogenet Genomics 17:127–136CrossRefPubMedGoogle Scholar
  45. 45.
    Spurdle AB, Chang JH, Byrnes GB, Chen X, Dite GS, McCredie MR, Giles GG, Southey MC, Chenevix-Trench G, Hopper JL (2007) A systematic approach to analysing gene-gene interactions: polymorphisms at the microsomal epoxide hydrolase EPHX and glutathione S-transferase GSTM1, GSTT1, and GSTP1 loci and breast cancer risk. Cancer Epidemiol Biomarkers Prev 16:769–774CrossRefPubMedGoogle Scholar
  46. 46.
    Steck SE, Gaudet MM, Britton JA, Teitelbaum SL, Terry MB, Neugut AI, Santella RM, Gammon MD (2007) Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk. Carcinogenesis 28:1954–1959CrossRefPubMedGoogle Scholar
  47. 47.
    Kadouri L, Kote-Jarai Z, Hubert A, Baras M, Abeliovich D, Hamburger T, Peretz T, Eeles RA (2008) Glutathione-S-transferase M1, T1 and P1 polymorphisms, and breast cancer risk, in BRCA1/2 mutation carriers. Br J Cancer 98:2006–2010CrossRefPubMedGoogle Scholar
  48. 48.
    Rajkumar T, Samson M, Rama R, Sridevi V, Mahji U, Swaminathan R, Nancy NK (2008) TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy. Breast Cancer Res Treat 112:81–87CrossRefPubMedGoogle Scholar
  49. 49.
    Sakoda LC, Blackston CR, Xue K, Doherty JA, Ray RM, Lin MG, Stalsberg H, Gao DL, Feng Z, Thomas DB, Chen C (2008) Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women. Breast Cancer Res Treat 109:143–155CrossRefPubMedGoogle Scholar
  50. 50.
    Saxena A, Dhillon VS, Raish M, Asim M, Rehman S, Shukla NK, Deo SV, Ara A, Husain SA (2009) Detection and relevance of germline genetic polymorphisms in glutathione S-transferases (GSTs) in breast cancer patients from northern Indian population. Breast Cancer Res Treat 115:537–543CrossRefPubMedGoogle Scholar
  51. 51.
    Syamala VS, Sreeja L, Syamala V, Raveendran PB, Balakrishnan R, Kuttan R, Ankathil R (2008) Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival. Fam Cancer 7:213–220CrossRefPubMedGoogle Scholar
  52. 52.
    Torresan C, Oliveira MM, Torrezan GT, de Oliveira SF, Abuazar CS, Losi-Guembarovski R, Lima RS, Urban CA, Cavalli IJ, Ribeiro EM (2008) Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes. Clin Exp Med 8:65–71CrossRefPubMedGoogle Scholar
  53. 53.
    Unlü A, Ates NA, Tamer L, Ates C (2008) Relation of glutathione S-transferase T1, M1 and P1 genotypes and breast cancer risk. Cell Biochem Funct 26:643–647CrossRefPubMedGoogle Scholar
  54. 54.
    Van Emburgh BO, Hu JJ, Levine EA, Mosley LJ, Perrier ND, Freimanis RI, Allen GO, Rubin P, Sherrill GB, Shaw CS, Carey LA, Sawyer LR, Miller MS (2008) Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer. Oncol Rep 19:1311–1321PubMedGoogle Scholar
  55. 55.
    Reding KW, Weiss NS, Chen C, Li CI, Carlson CS, Wilkerson HW, Farin FM, Thummel KE, Daling JR, Malone KE (2009) Genetic polymorphisms in the catechol estrogen metabolism pathway and breast cancer risk. Cancer Epidemiol Biomarkers Prev 18:1461–1467CrossRefPubMedGoogle Scholar
  56. 56.
    The MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk (2009) Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women. Breast Cancer Res Treat. doi: 10.1007/s10549-009-0407-0
  57. 57.
    Sgambato A, Campisi B, Zupa A (2002) Glutathione S-transferase (GST) polymorphisms as risk factors for cancer in a highly homogeneous population from southern Italy. Anticancer Res 22:3647–3652PubMedGoogle Scholar
  58. 58.
    Bailey LR, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl FF (1998) Breast cancer and CYPIA1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58:65–70PubMedGoogle Scholar
  59. 59.
    McCready D, Aronson KJ, Chu W, Fan W, Vesprini D, Narod SA (2004) Breast tissue organochlorine levels and metabolic genotypes in relation to breast cancer risk Canada. Cancer Causes Control 15:399–418CrossRefPubMedGoogle Scholar
  60. 60.
    Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRefGoogle Scholar
  61. 61.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  62. 62.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  63. 63.
    Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8:15–17Google Scholar
  64. 64.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  65. 65.
    Salinas AE, Wong MG (1999) Glutathione S-transferases—a review. Curr Med Chem 6:279–309PubMedGoogle Scholar
  66. 66.
    Hirschhorn JN, Lohmueller K, Byrne E (2002) A comprehensive review of genetic association studies. Genet Med 4:45–61CrossRefPubMedGoogle Scholar
  67. 67.
    Wacholder S, Chanock S, Garcia-Closas M (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96:434–442PubMedCrossRefGoogle Scholar
  68. 68.
    Kaaks R, Rinaldi S, Key TJ (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12:1071–1082CrossRefPubMedGoogle Scholar
  69. 69.
    Key T, Appleby P, Barnes I, Reeves G (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Li-Xin Qiu
    • 1
    • 2
  • Hui Yuan
    • 3
  • Ke-Da Yu
    • 2
    • 4
  • Chen Mao
    • 5
  • Bo Chen
    • 6
  • Ping Zhan
    • 7
  • Kai Xue
    • 1
    • 2
  • Jian Zhang
    • 1
    • 2
  • Xi-Chun Hu
    • 1
    • 2
  1. 1.Department of Medical OncologyCancer Hospital, Fudan UniversityShanghaiChina
  2. 2.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityAnhuiChina
  4. 4.Breast Cancer Institute, Department of Breast SurgeryCancer Hospital, Fudan UniversityShanghaiChina
  5. 5.Department of Epidemiology, School of Public Health and Tropical MedicineSouthern Medical UniversityGuangzhouChina
  6. 6.Department of Geriatrics, First Affiliated HospitalNanjing Medical UniversityNanjingChina
  7. 7.Department of Respiratory MedicineNanjing Chest HospitalNanjingChina

Personalised recommendations