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Breast Cancer Research and Treatment

, Volume 115, Issue 3, pp 537–543 | Cite as

Detection and relevance of germline genetic polymorphisms in glutathione S-transferases (GSTs) in breast cancer patients from northern Indian population

  • Anubha Saxena
  • Varinderpal S. Dhillon
  • Mohammad Raish
  • Mohammad Asim
  • Shabeena Rehman
  • N. K. Shukla
  • S. V. S. Deo
  • Anjum Ara
  • Syed Akhtar Husain
Preclinical Study

Abstract

Introduction Glutathione S-transferases (GSTs) are polymorphic superfamily of detoxification enzymes that detoxify therapeutic drugs and various carcinogens. We undertook a case–control study in northern Indian population based sample consisting of 413 patients and 410 controls to evaluate association of null genotype in GSTM1 and GSTT1 along with polymorphism in GSTP1 (A→G) with breast cancer risk. Methods Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) were calculated by unconditional logistic regression analysis adjusting for various confounding factors. Results In this case–control study, we observed a positive correlation between family history of breast cancer and risk of breast cancer (OR = 2.06; 95% CI = 1.47–2.92). We found a significantly increased breast cancer risk associated with GSTM1 null genotype (OR = 2.28; 95% CI = 1.65–2.97) and homozygote mutants in GSTP1 (OR = 2.59; 95% CI = 1.67–4.39). However, we found no association between GSTT1 null genotype with overall breast cancer risk (OR = 1.04; 95% CI = 0.76–1.59). The three-way combination of GSTP1 105AA/AG and null genotypes for both GSTM1 and GSTT1 resulted in fourfold increase in breast cancer risk (OR = 4.02; 95% CI = 1.99–8.51). Conclusion The findings of this study are in line with previously published reports that show an overall association with GSTM1 and GSTP1 polymorphisms with breast cancer risk. Our results suggest that the variants in low penetrance genes such as GSTM1, GSTT1 and GSTP1 are associated with an increased breast cancer risk thereby suggesting their contribution in the etiology of breast cancer.

Keywords

GSTM1 GSTT1 GSTP1 Polymorphism Breast cancer 

References

  1. 1.
    Smith G, Stanley LA, Sim E, Strange RC, Wolf CR (1995) Metabolic polymorphism and cancer susceptibility. Cancer Surv 25:27–65PubMedGoogle Scholar
  2. 2.
    Ketterer B (1998) The protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis. Mutat Res 202:343–361. doi: 10.1016/0027-5107(88)90197-2 Google Scholar
  3. 3.
    Salinas AE, Wong MG (1999) Glutathione S-transferases—a review. Curr Med Chem 6:279–309PubMedGoogle Scholar
  4. 4.
    Strange RC, Lear JT, Fryer AA (1998) Glutathione-S-transferase polymorphisms: influence on susceptibility to cancer. Chem Biol Interact 111–112:351–364PubMedCrossRefGoogle 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.
    Pearson WR, Vorachek WR, Xu SJ, Berger R, Hart I, Vannais D et al (1993) Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet 53:220–233PubMedGoogle Scholar
  7. 7.
    Nelson HH, Wiencke JK, Christiani DC, Cheng TJ, Zuo ZF, Schwartz BS (1995) Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta. Carcinogenesis 16:1243–1245. doi: 10.1093/carcin/16.5.1243 PubMedCrossRefGoogle Scholar
  8. 8.
    Kelley MK, Engquist-Goldstein A, Montali JA, Wheatley JB, Schmidt DE Jr, Kauvar LM (1994) Variability of glutathione s-transferase isoenzyme patterns in normal and cancer human breast tissue. Biochem J 300:843–848Google Scholar
  9. 9.
    Hayes JD, Strange RC (2000) Glutathione s-transferase polymorphisms and their biological consequences. Pharmacology 61:154–166. doi: 10.1159/000028396 PubMedCrossRefGoogle Scholar
  10. 10.
    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 30:445–600. doi: 10.3109/10409239509083491 PubMedCrossRefGoogle Scholar
  11. 11.
    Hengstler JG, Arand M, Herrero ME, Oesch F (1998) Polymorphisms in Nacetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent Results Cancer Res 154:47–85PubMedGoogle Scholar
  12. 12.
    Maugard CM, Charrier J, Bignon YJ (1998) Allelic deletion at glutathione S-transferase M1 locus and its association with breast cancer susceptibility. Chem Biol Interact 11–112:365–375CrossRefGoogle Scholar
  13. 13.
    Helzlsouer KJ, Selmin O, Huang H-Y, Strickland PT, Hoffman S, Alberg AJ et al (1998) Association between glutathione Stransferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J Natl Cancer Inst 90:512–518. doi: 10.1093/jnci/90.7.512 PubMedCrossRefGoogle Scholar
  14. 14.
    Mitrunen K, Jourenkova N, Kataja V, Eskelinen M, Kosma VM, Benhamou S et al (2001) Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. Cancer Epidemiol Biomarkers Prev 10:229–236PubMedGoogle Scholar
  15. 15.
    Spurdle AB, Chang JH, Byrnes GB, Chen X, Dite GS, McCredie MR 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 16:769–774. doi: 10.1158/1055-9965.EPI-06-0776 PubMedCrossRefGoogle Scholar
  16. 16.
    Steck SE, Gaudet MM, Britton JA, Teitelbaum SL, Terry MB, Neugut AI et al (2007) Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk. Carcinogenesis 28:1954–1959. doi: 10.1093/carcin/bgm141 PubMedCrossRefGoogle Scholar
  17. 17.
    Syamala VS, Sreeja L, Syamala V, Raveendran PB, Balakrishnan R, Kuttan R et al (2007) Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival. Fam Cancer. doi: 10.1007/s10689-007-9177-1
  18. 18.
    Garcıa-Closas M, Kelsey KT, Hankinson DS, Springer K, Willett WC, Speizer FE et al (1999) Glutathione S-transferase m and u polymorphisms and breast cancer susceptibility. J Natl Cancer Inst 91:1960–1964. doi: 10.1093/jnci/91.22.1960 PubMedCrossRefGoogle Scholar
  19. 19.
    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
  20. 20.
    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
  21. 21.
    Egan KM, Cai Q, Shu XO, Jin F, Zhu TL, Dai Q et al (2004) Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai breast cancer study and metaanalysis. Cancer Epidemiol Biomarkers Prev 13:197–204. doi: 10.1158/1055-9965.EPI−03-0294 PubMedCrossRefGoogle Scholar
  22. 22.
    Vogl FD, Taioli E, Maugard C, Zheng W, Pinto LF, Ambrosone C et al (2004) Glutathione S-transferases M1, T1, and P1 and breast cancer: a pooled analysis. Cancer Epidemiol Biomarkers Prev 13:1473–1479PubMedGoogle Scholar
  23. 23.
    Bailey LR, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl FF (1998) Breast cancer and CYP1A1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58:65–70PubMedGoogle Scholar
  24. 24.
    Millikan R, Pittman G, Tse C-K, 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
  25. 25.
    Zhao M, Lewis R, Gustafson DR, Wen W-Q, Cerhan JR, Zheng W (2001) No apparent association of GSTP1 A313G polymorphism with breast cancer risk among postmenopausal Iowa women. Cancer Epidemiol Biomarkers Prev 10:1301–1302PubMedGoogle Scholar
  26. 26.
    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 Biomarkers Prev 8:843–854PubMedGoogle Scholar
  27. 27.
    Samson M, Swaminathan R, Rama R, Sridevi V, Nancy KN, Rajkumar T (2007) Role of GSTM1 (null/present), GSTP1 (Ile105Val) and P53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer: a case control study from South India. Asian Pac J Cancer Prev 8:253–257PubMedGoogle Scholar
  28. 28.
    Park SK, Yim DS, Yoon KS, Choi IM, Choi JY, Yoo KY et al (2004) Combined effect of GSTM1, GSTT1, and COMT genotypes in individual breast cancer risk. Breast Cancer Res Treat 88:55–62. doi: 10.1007/s10549-004-0745-x PubMedCrossRefGoogle Scholar
  29. 29.
    Bernardini S, Bellincampi L, Ballerini S, Federici G, Iori R, Trequattrini A et al (2005) Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele. Clin Chem 51:944–951. doi: 10.1373/clinchem.2004.045955 PubMedCrossRefGoogle Scholar
  30. 30.
    Johansson AS, Stenberg G, Widersten M, Mannervik B (1998) Structure activity relationships and thermal stability of human glutathione transferase P1-1 governed by the H-site residue 105. J Mol Biol 278:687–698. doi: 10.1006/jmbi.1998.1708 PubMedCrossRefGoogle Scholar
  31. 31.
    Chan QK, Khoo US, Ngan HY, Yang CQ, Xue WC, Chan KY et al (2005) Single nucleotide polymorphism of pi-class glutathione S-transferase and susceptibility to endometrial carcinoma. Clin Cancer Res 11:2981–2985. doi: 10.1158/1078-0432.CCR-04-2038 PubMedCrossRefGoogle Scholar
  32. 32.
    Warholm M, Guthenberg C, Mannervik B (1983) Molecular and catalytic properties of glutathione transferase μ from human liver: an enzyme efficiently conjugating epoxides. Biochemistry 22:3610–3617. doi: 10.1021/bi00284a011 PubMedCrossRefGoogle Scholar
  33. 33.
    Grover PL, Martin FL (2002) The initiation of breast and prostate cancer. Carcinogenesis 23:1095–1102. doi: 10.1093/carcin/23.7.1095 PubMedCrossRefGoogle Scholar
  34. 34.
    Li D, Wang M, Dhingra K, Hittelman WN (1996) Aromatic DNA adducts in adjacent tissues of breast cancer patients: clues to breast cancer etiology. Cancer Res 56:287–293PubMedGoogle Scholar
  35. 35.
    Phillips DH (1999) Polycyclic aromatic hydrocarbons in the diet. Mutat Res 443:139–147PubMedGoogle Scholar
  36. 36.
    Baron JA, La Vecchia C, Levi F (1990) The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol 162:502–514PubMedGoogle Scholar
  37. 37.
    Terry PD, Rohan TE (2002) Cigarette smoking and the risk of breast cancer in women: a review of the literature. Cancer Epidemiol Biomarkers Prev 11:953–971PubMedGoogle Scholar
  38. 38.
    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 109:143–155. doi: 10.1007/s10549-007-9633-5 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Anubha Saxena
    • 1
  • Varinderpal S. Dhillon
    • 2
  • Mohammad Raish
    • 1
  • Mohammad Asim
    • 3
  • Shabeena Rehman
    • 1
  • N. K. Shukla
    • 4
  • S. V. S. Deo
    • 4
  • Anjum Ara
    • 5
  • Syed Akhtar Husain
    • 1
  1. 1.Human Genetics Laboratory, Department of BiosciencesJamia Millia Islamia, A Central UniversityNew DelhiIndia
  2. 2.Genome Health and Nutrigenomics LaboratoryCSIRO Human NutritionAdelaideAustralia
  3. 3.Department of MedicineMaulana Azad Medical CollegeNew DelhiIndia
  4. 4.Department of Surgical OncologyInstitute Rotary Cancer Hospital, All India Institute of Medical SciencesNew DelhiIndia
  5. 5.Department of Zoology, Women’s CollegeAligarh Muslim UniversityAligarhIndia

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