Skip to main content

Advertisement

SpringerLink
Log in

Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival

  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

Identifying genes associated with familial inheritance of breast cancer continues to be a major goal of current research as the known high penetrance genes could be attributable for only a small percentage of the risk. So, it is hypothesized that the low penetrance genes may also modify the risk for familial breast cancer. In the present case–control study, undertaken to examine the influence of polymorphisms of GSTs in familial and sporadic breast cancer susceptibility, 597 women including 222 sporadic breast cancer patients, 125 familial breast cancer patients and 250 females with no history of cancer as controls were genotyped by PCR based methods. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Interestingly, GSTM1 deletion was found to be significantly associated only with familial breast cancer (OR = 2.0; 95%CI = 1.252–3.128) while GSTT1 was associated only with sporadic breast cancer (OR = 2.3; 95%CI = 1.336–3.970). GSTP1 Ile105Val polymorphism was associated neither with sporadic nor familial breast cancer susceptibility (P value > 0.05). The GST genotypes did not have any effect on the survival of both familial and sporadic breast cancer patients. However, familial breast cancer patients with GSTM1 null genotype had a relative risk of 0.42 (95%CI = 0.18–0.97) for an advanced disease stage. The results indicate that, in addition to the known high penetrance genes, certain low penetrance genes may also play a role, in the familial inheritance of breast cancer. It is also noticed that all the polymorphisms associated with sporadic breast cancer are not associated with familial breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 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 272:10004–10012

    Article  PubMed  CAS  Google Scholar 

  2. Ambrosone CB, Freudenheim JL, Graham S et al (1995) Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and postmenopausal breast cancer risk. Cancer Res 55:3483–3485

    PubMed  CAS  Google Scholar 

  3. Ambrosone CB, Sweeney C, Coles BF et al (2001) Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer. Cancer Res 19:7130–7135

    Google Scholar 

  4. Bell DA, Taylor JA, Paulson DF et al (1993) Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 85:1159–1164

    Article  PubMed  CAS  Google Scholar 

  5. Chacko P, Joseph T, Mathew BS et al (2005) Role of xenobiotic metabolizing gene polymorphisms in breast cancer susceptibility and treatment outcome. Mutat Res 581:153–163

    PubMed  CAS  Google Scholar 

  6. Chen CL, Liu Q, Relling MV (1996) Simultaneous characterization of glutathione S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmacogenetics 6:187–191

    Article  PubMed  CAS  Google Scholar 

  7. Curran JE, Weinstein SR, Griffiths LR (2000) Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility. Cancer Lett 153:113–120

    Article  PubMed  CAS  Google Scholar 

  8. DeMichele A, Aplenc R, Botbyl J et al (2005) Drug-metabolizing enzyme polymorphisms predict clinical outcome in a node-positive breast cancer cohort. J Clin Oncol 23:5552–5559

    Article  PubMed  CAS  Google Scholar 

  9. Easton DF (1999) How many more breast cancer predisposition genes are there? Breast Cancer Res 1:14–17

    Article  PubMed  CAS  Google Scholar 

  10. 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 13:197–204

    Article  PubMed  CAS  Google Scholar 

  11. Ford D, Easton DF, Stratton M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast cancer linkage consortium. Am J Hum Genet 62:676–689

    Article  PubMed  CAS  Google Scholar 

  12. Garcia-Closas M, Kelsey KT, Hankinson SE et al (1999) Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility. J Natl Cancer Inst 91:1960–1964

    Article  PubMed  CAS  Google Scholar 

  13. 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 10:1169–1173

    PubMed  CAS  Google Scholar 

  14. Hamajima N, Takezaki T, Tajima K (2002) Allele Frequencies of 25 Polymorphisms pertaining to cancer risk for Japanese, Koreans and Chinese. Asian Pac J Cancer Prev 3:197–206

    PubMed  Google Scholar 

  15. Harries LW, Stubbins MJ, Forman D et al (1997) Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 18:641–644

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. Helzlsouer KJ, Selmin O, Huang HY et al (1998) Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J Natl Cancer Inst 90:512–518

    Article  PubMed  CAS  Google Scholar 

  18. IARC (1989) IARC Monographs on the evaluation of carcinogenic risks to humans, Vol 43, diesel and gasoline engine exhausts and some nitroarenes. Lyon, 41–185

  19. Joseph T, Kusumakumary P, Chacko P et al (2004) Genetic polymorphism of CYP1A1, CYP2D6, GSTM1 and GSTT1 and susceptibility to acute lymphoblastic leukaemia in Indian children. Pediatr Blood Cancer 43:560–567

    Article  PubMed  Google Scholar 

  20. Kelsey KT, Hankinson SE, Colditz GA et al (1997) Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases. Cancer Epidemiol Biomarkers Prev 6:511–515

    PubMed  CAS  Google Scholar 

  21. Ketterer B (1998) Glutathione S-transferases and prevention of cellular free radical damage. Free Radic Res 28:647–658

    Article  PubMed  CAS  Google Scholar 

  22. Khedhaier A, Remadi S, Corbex M et al (2003) Glutathione S-transferases (GSTT1 and GSTM1) gene deletions in Tunisians: susceptibility and prognostic implications in breast carcinoma. Br J Cancer 89:1502–1507

    Article  PubMed  CAS  Google Scholar 

  23. Kim SU, Lee KM, Park SK et al (2004) Genetic polymorphism of glutathione S-transferase P1 and breast cancer risk. J Biochem Mol Biol 37:582–585

    PubMed  CAS  Google Scholar 

  24. Lizard-Nacol S, Coudert B, Colosetti P et al (1999) Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer. Breast Cancer Res 1:81–87

    Article  PubMed  CAS  Google Scholar 

  25. 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 9:567–573

    PubMed  CAS  Google Scholar 

  26. 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 10:229–236

    PubMed  CAS  Google Scholar 

  27. Nathanson KL, Weber BL (2001) Other breast cancer susceptibility genes: searching for more holy grail. Hum Mol Genet 10:715–720

    Article  PubMed  CAS  Google Scholar 

  28. Nedelcheva KV, Andersen TI, Erikstein B et al (1998) Single tube multiplex polymerase chain reaction genotype analysis of GSTM1, GSTT1 and GSTP1: relation of genotypes to TP53 tumor status and clinicopathological variables in breast cancer patients. Pharmacogenetics 8:441–447

    Article  Google Scholar 

  29. Park SK, Yoo KY, Lee SJ et al (2000) Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk. Pharmacogenetics 10:301–309

    Article  PubMed  CAS  Google Scholar 

  30. Pemble S, Schroeder KR, Spencer SR et al (1994) Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300(Pt 1):271–276

    PubMed  CAS  Google Scholar 

  31. Ryberg D, Skaug V, Hewer A et al (1997) Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis 18:1285–1289

    Article  PubMed  CAS  Google Scholar 

  32. Samson M, Swaminathan R, Rama R et al (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(2):253–257

    PubMed  Google Scholar 

  33. Seidegard J, Vorachek WR, Pero RW et al (1988) Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci USA 85:7293–7297

    Article  PubMed  CAS  Google Scholar 

  34. Serova OM, Mazoyer S, Puget N et al (1997) Mutations in BRCA1 and BRCA2 in breast cancer families: are there more breast cancer-susceptibility genes? Am J Hum Genet 60:486–495

    PubMed  CAS  Google Scholar 

  35. Sreeja L, Syamala V, Hariharan S et al (2005) Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population. J Hum Genet 50:618–627

    Article  PubMed  CAS  Google Scholar 

  36. Sreelekha TT, Ramadas K, Pandey M et al (2001) Genetic polymorphism of CYP1A1, GSTM1 and GSTT1 genes in Indian oral cancer. Oral Oncol 37:593–598

    Article  PubMed  CAS  Google Scholar 

  37. Strange RC, Spiteri MA, Ramachandran S et al (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482:21–26

    PubMed  CAS  Google Scholar 

  38. Sundberg K, Johansson AS, Stenberg G et al (1998) Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1–1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons. Carcinogenesis 19:433–436

    Article  PubMed  CAS  Google Scholar 

  39. Sweeney C, Ambrosone CB, Joseph L et al (2003) Association between a glutathione S-transferase A1 promoter polymorphism and survival after breast cancer treatment. Int J Cancer 103:810–814

    Article  PubMed  CAS  Google Scholar 

  40. Yang G, Shu XO, Ruan ZX et al (2005) Genetic polymorphisms in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma. Cancer 103:52–58

    Article  PubMed  CAS  Google Scholar 

  41. 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 224:893–899

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We express our sincere thanks and gratitude to Dr. Beela Sarah Mathew and Dr. Lekshmy for their help in patient selection.

Author information

Authors and Affiliations

  1. Division of Cancer Research, Regional Cancer Centre, Trivandrum , 695011, Kerala, India

    Volga S. Syamala, Leelakumari Sreeja, Vani Syamala, Praveenkumar B. Raveendran & Ravindran Ankathil

  2. Division of Radiation Oncology, Regional Cancer Centre, Trivandrum , 695011, Kerala, India

    Rajan Balakrishnan & Ratheesan Kuttan

Authors
  1. Volga S. Syamala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leelakumari Sreeja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vani Syamala
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Praveenkumar B. Raveendran
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rajan Balakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ratheesan Kuttan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ravindran Ankathil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ravindran Ankathil.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Syamala, V.S., Sreeja, L., Syamala, V. et al. Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival. Familial Cancer 7, 213–220 (2008). https://doi.org/10.1007/s10689-007-9177-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-007-9177-1

Keywords

Search

Navigation