Breast Cancer Research and Treatment

, Volume 125, Issue 1, pp 253–259 | Cite as

Glutathione S-transferase P1 Ile105Val polymorphism and breast cancer risk: a meta-analysis involving 34,658 subjects



Glutathione S-transferase P1 (GSTP1) is involved in a wide range of detoxifying reactions. Any alteration in the structure, function, or expression of GSTP1 gene may alter the ability of a cell to inactivate carcinogens or mutagens, and thus modify an individual’s risk to cancer. Previous epidemiological studies on the potential association between GSTP1 Ile105Val polymorphism and breast cancer risk have produced inconsistent results. In order to drive a more precise estimation of this association, we performed a meta-analysis of 30 published case–control studies including 15,901 cases and 18,757 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The results of this meta-analysis showed that GSTP1 Ile105Val polymorphism was not associated with breast cancer susceptibility in overall population. However, in subgroup analysis by ethnicity, we found a significant association among Asian population (for Val/Val vs. Ile/Ile: OR 1.27, 95% CI 1.02–1.83; for the recessive model Val/Val vs. Ile/Ile + Ile/Val: OR 1.42, 95% CI 1.20–1.69). When stratified by study design, significantly elevated susceptibility to breast cancer was found among hospital-based studies (for Val/Val vs. Ile/Ile: OR 1.38, 95% CI 1.16–1.63; for recessive model Val/Val vs. Ile/Val + Ile/Ile: OR 1.31, 95% CI 1.12–1.55; for dominant model: Val/Val + Ile/Val vs. Ile/Ile: OR 1.10, 95% CI 1.02–1.19). In conclusion, our meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase susceptibility to breast cancer in Asian population.


GSTP1 Polymorphism Breast cancer Meta-analysis 


  1. 1.
    Ghadirian P, Lacroix A, Perret C, Robidoux A, Falardeau M, Maisonneuve P et al (1998) Breast cancer risk and nutrient intake among French Canadians in Montreal: a case–control study. Breast 7:108–113CrossRefGoogle Scholar
  2. 2.
    Henderson IC (1993) Risk factors for breast cancer development. Cancer 71:2127–2140CrossRefPubMedGoogle Scholar
  3. 3.
    Harris JR, Lippman ME, Veronesi U, Willett W (1992) Breast cancer (1). N Engl J Med 327:319–328CrossRefPubMedGoogle Scholar
  4. 4.
    Ketterer B (1998) The protective tole of glutathione and glutathione transferases in mutagenesis and carcinogenesis. Mutat Res 202:343–361Google Scholar
  5. 5.
    Board PG, Baker RT, Chelvanayagam G, Jermiin LS (1997) Zeta, a novel class of glutathione transferases in a range of species from plants to humans. Biochem J 328:929–935PubMedGoogle Scholar
  6. 6.
    Albin N, Massaad L, Toussaint C, Mathieu MC, Morizet J, Parise O, Gouyette A, Chabot GG (1993) Main drug metabolizing enzyme systems in human breast tumors and peritumoral tissues. Cancer Res 53:3541–3546PubMedGoogle Scholar
  7. 7.
    Forrester LM, Hayes JD, Millis R, Barnes D, Harris AL, Schlager JJ, Powis G, Wolf CR (1990) Expression of glutathione S-transferases and cytochrome P450 in normal and tumor breast tissue. Carcinogenesis 11:2163–2170CrossRefPubMedGoogle Scholar
  8. 8.
    Shea TC, Claflin G, Comstock KE, Sanderson BJ, Burstein NA, Keenan EJ, Mannervik B, Henner WD (1990) Glutathione transferase activity and isoenzyme composition in primary human breast cancers. Cancer Res 50:6848–6853PubMedGoogle Scholar
  9. 9.
    Whalen R, Boyer TD (1998) Human glutathione S-transferases. Semin Liver Dis 18(4):345–358CrossRefPubMedGoogle Scholar
  10. 10.
    Zimniak P, Nanduri B, Pikula S et al (1994) Naturally occurring human glutathione S-transferase GSTP1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties. Eur J Biochem 224:893–899CrossRefPubMedGoogle Scholar
  11. 11.
    Ali-Osman F, Akande O, Antoun G et al (1997) Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 272(15):10004–10012CrossRefPubMedGoogle Scholar
  12. 12.
    Harries LW, Stubbins MJ, Forman G, Howard GC, Wolf CR (1997) Identification of genetic polymorphism at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 18:641–644CrossRefPubMedGoogle Scholar
  13. 13.
    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(7):512–518CrossRefPubMedGoogle Scholar
  14. 14.
    Curran JE, Weinstein SR, Griffiths LR (2000) Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility. Cancer Lett 153(1–2):113–120CrossRefPubMedGoogle Scholar
  15. 15.
    Millikan R, Pittman G, Tse CK et al (2000) Glutathione S-transferases M1, T1, and P1 and breast cancer. Cancer Epidemiol Biomarkers Prev 9(6):567–573PubMedGoogle Scholar
  16. 16.
    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(2):220–225CrossRefPubMedGoogle Scholar
  17. 17.
    Zhao M, Lewis R, Gustafson DR et al (2001) No apparent association of GSTP1 A(313)G polymorphism with breast cancer risk among postmenopausal Iowa women. Cancer Epidemiol Biomarkers Prev 10(12):1301–1302PubMedGoogle Scholar
  18. 18.
    Mitrunen K, Jourenkova N, Kataja V et al (2001) Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. Cancer Epidemiol Biomarkers Prev 10(3):229–236PubMedGoogle Scholar
  19. 19.
    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(11):1169–1173PubMedGoogle Scholar
  20. 20.
    Kim SU, Lee KM, Park SK et al (2004) Genetic polymorphism of glutathione S-transferase P1 and breast cancer risk. J Biochem Mol Biol 37(5):582–585PubMedGoogle Scholar
  21. 21.
    Egan KM, Cai Q, Shu XO et al (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(2):197–204CrossRefPubMedGoogle Scholar
  22. 22.
    Sarmanová J, Sůsová S, Gut I, Mrhalová M, Kodet R, Adámek J, Roth Z, Soucek P (2004) Breast cancer: role of polymorphisms in biotransformation enzymes. Eur J Hum Genet 12(10):848–854CrossRefPubMedGoogle Scholar
  23. 23.
    Nordgard SH, Ritchie MD, Jensurd SD et al (2007) ABCB1 and GST polymorphisms associated with TP53 status in breast cancer. Pharmacogenet Genomics 17:127–136CrossRefPubMedGoogle Scholar
  24. 24.
    Edvardsen H, Kristensen VN, Grenaker Alnaes GI, Bøhn M, Erikstein B, Helland A, Børrensen-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(4):1163–1171CrossRefPubMedGoogle Scholar
  25. 25.
    Spurdle AB, Chang JH, Byrnes GB et al (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(4):769–774CrossRefPubMedGoogle Scholar
  26. 26.
    Syamala VS, Sreeja L, Syamala V, Raveendran PB, Balakrishnan R, Kuttan R et al (2008) Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival. Fam Cancer 7(3):213–220CrossRefPubMedGoogle Scholar
  27. 27.
    Sakoda LC, Blackston CR, Xue K, Doherty JA, Ray RM, Lin MG et al (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
  28. 28.
    Van Emburgh BO, Hu JJ, Levine EA et al (2008) Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer. Oncol Rep 19(5):1311–1321PubMedGoogle Scholar
  29. 29.
    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(12):2006–2010CrossRefPubMedGoogle Scholar
  30. 30.
    Antognelli C, Del Buono C, Ludovini V, Gori S, Talesa VN, Crinò L, Barberini F, Rulli A (2009) CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer: an Italian case–control study. BMC Cancer 9:115CrossRefPubMedGoogle Scholar
  31. 31.
    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(3):537–543CrossRefPubMedGoogle Scholar
  32. 32.
    Reding KW, Weiss NS, Chen C et al (2009) Genetic polymorphisms in the catechol estrogen metabolism pathway and breast cancer risk. Cancer Epidemiol Biomarkers Prev 18(5):1461–1467CrossRefPubMedGoogle Scholar
  33. 33.
    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 119(2):463–474CrossRefGoogle Scholar
  34. 34.
    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
  35. 35.
    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
  36. 36.
    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
  37. 37.
    Unlu 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
  38. 38.
    Maugard CM, Charrier J, Pitard A, Campion L, Akande O, Pleasants L, Ali-Osman F (2001) Genetic polymorphism at the glutathione S-transferase (GST) P1 locus is a breast cancer risk modifier. Int J Cancer 91:334–339CrossRefPubMedGoogle Scholar
  39. 39.
    Lee SA, Fowke JH, Lu W, Ye C, Zheng Y, Cai Q, Gu K, Gao YT, Shu XO, Zheng W (2008) Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk. Am J Clin Nutr 87:753–760PubMedGoogle Scholar
  40. 40.
    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 156:300–310PubMedGoogle Scholar
  41. 41.
    Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826PubMedGoogle Scholar
  42. 42.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  43. 43.
    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
  44. 44.
    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
  45. 45.
    Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:445–600CrossRefPubMedGoogle Scholar
  46. 46.
    Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D (2000) Estrogens as endogenous genotoxic agents: DNA adducts and mutations. J Natl Cancer Inst Monogr 27:75–93PubMedGoogle Scholar
  47. 47.
    Dawling S, Hachey DL, Roodi N, Parl FF (2004) In vitro model of mammary estrogen metabolism: structural and kinetic differences between catechol estrogen 2-and 4-hydroxyestradiol. Chem Res Toxicol 17:1258–1264CrossRefPubMedGoogle Scholar
  48. 48.
    Garcia-Saéz I, Parraga A, Phillips MF, Mantle TJ, Coll M (1994) Molecular structure of 1.8 Å of mouse liver class pi glutathione S-transferase complex with s-(p-nitrobenzyl) glutathione and other inhibitors. J Mol Biol 237:298–314CrossRefPubMedGoogle Scholar
  49. 49.
    Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF (1999) A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomark Prev 8:843–854Google Scholar
  50. 50.
    Hirschhorn JN, Lohmueller K, Byrne E (2002) A comprehensive review of genetic association studies. Genet Med 4:45–46CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  1. 1.Second Department of Breast TumorTianjin Medical University Cancer Institute and HospitalTianjinChina
  2. 2.Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical University, Ministry of EducationTianjinChina
  3. 3.Key Laboratory of Cancer Prevention and TherapyTianjinChina
  4. 4.Department of Epidemiology and BiostatisticsNanjing Medical UniversityNanjingChina
  5. 5.Department of Epidemiology and BiostatisticsPublic Health School of Zhengzhou UniversityZhengzhouChina

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