Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Jan;79(2):346–353. doi: 10.1038/sj.bjc.6690055

Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility

J Charrier 1,2,#, C M Maugard 1,2,#, B Le Mevel 1, Y J Bignon 2
PMCID: PMC2362188  PMID: 9888479

Abstract

The influence of polymorphisms of the glutathione S-transferase gene GSTM1 in breast cancer susceptibility has been assessed in this study. Previous studies correlated the absence of the GSTM1 protein with an increased risk of developing some cancers, especially lung or bladder cancers, in heavy smokers. In this study, we determined GSTM1 polymorphisms in a population of 437 female controls from the west of France and 361 community breast cancer patients. Three distinct alleles of this gene exist: GSTM1* A, GSTM1*B and GSTM1*0 (deleted allele). Null subjects (GSTM1 null) are homozygous for this deletion. The comparative analysis of GSTM1 allelotypes in our two populations did not demonstrate a statistically significant difference in distribution (P = 0.22), although the null genotype was more frequent in cancer patients. However, breast cancer risk was increased in null subjects ≥ 50 years of age compared with non-null subjects [odds ratio = 1.99 (1.19–3.32), P = 0.009], but not in null subjects < 50 years of age compared with non-null subjects (P = 0.86). Our results suggest that the GSTM1 null genotype may play a role in post-menopausal breast cancer development. They also point to a putative protective role of the A allele in the older female control group, especially in hemizygous subjects [odds ratio = 0.42 (0.23–0.77), P = 0.03]. © 1999 Cancer Research Campaign

Keywords: cancer susceptibility, breast cancer, glutathione S-transferase, allelic polymorphism

Full Text

The Full Text of this article is available as a PDF (101.8 KB).

Footnotes

Preliminary results of this study were presented as oral communication during the international conference on glutathione and related enzymes in Hilton Head (North Carolina, October 1996).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambrosone C. B., Freudenheim J. L., Graham S., Marshall J. R., Vena J. E., Brasure J. R., Laughlin R., Nemoto T., Michalek A. M., Harrington A. Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and postmenopausal breast cancer risk. Cancer Res. 1995 Aug 15;55(16):3483–3485. [PubMed] [Google Scholar]
  2. Claus E. B. Genetic epidemiology of breast cancer in younger women. J Natl Cancer Inst Monogr. 1994;(16):49–53. [PubMed] [Google Scholar]
  3. Comstock K. E., Sanderson B. J., Claflin G., Henner W. D. GST1 gene deletion determined by polymerase chain reaction. Nucleic Acids Res. 1990 Jun 25;18(12):3670–3670. doi: 10.1093/nar/18.12.3670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Doll R., Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst. 1981 Jun;66(6):1191–1308. [PubMed] [Google Scholar]
  5. Duncan H., Swan C., Green J., Jones P., Brannigan K., Alldersea J., Fryer A. A., Strange R. C. Susceptibility to ulcerative colitis and Crohn's disease: interactions between glutathione S-transferase GSTM1 and GSTT1 genotypes. Clin Chim Acta. 1995 Aug 31;240(1):53–61. doi: 10.1016/0009-8981(95)06127-4. [DOI] [PubMed] [Google Scholar]
  6. Easton D. Breast cancer genes--what are the real risks? Nat Genet. 1997 Jul;16(3):210–211. doi: 10.1038/ng0797-210. [DOI] [PubMed] [Google Scholar]
  7. Easton D., Ford D., Peto J. Inherited susceptibility to breast cancer. Cancer Surv. 1993;18:95–113. [PubMed] [Google Scholar]
  8. Franceschi S., la Vecchia C., Negri E., Parazzini F., Boyle P. Breast cancer risk and history of selected medical conditions linked with female hormones. Eur J Cancer. 1990;26(7):781–785. doi: 10.1016/0277-5379(90)90151-i. [DOI] [PubMed] [Google Scholar]
  9. Fryer A. A., Zhao L., Alldersea J., Boggild M. D., Perrett C. W., Clayton R. N., Jones P. W., Strange R. C. The glutathione S-transferases: polymerase chain reaction studies on the frequency of the GSTM1 0 genotype in patients with pituitary adenomas. Carcinogenesis. 1993 Apr;14(4):563–566. doi: 10.1093/carcin/14.4.563. [DOI] [PubMed] [Google Scholar]
  10. Fryer A. A., Zhao L., Alldersea J., Pearson W. R., Strange R. C. Use of site-directed mutagenesis of allele-specific PCR primers to identify the GSTM1 A, GSTM1 B, GSTM1 A,B and GSTM1 null polymorphisms at the glutathione S-transferase, GSTM1 locus. Biochem J. 1993 Oct 1;295(Pt 1):313–315. doi: 10.1042/bj2950313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Harada S., Misawa S., Nakamura T., Tanaka N., Ueno E., Nozoe M. Detection of GST1 gene deletion by the polymerase chain reaction and its possible correlation with stomach cancer in Japanese. Hum Genet. 1992 Sep-Oct;90(1-2):62–64. doi: 10.1007/BF00210745. [DOI] [PubMed] [Google Scholar]
  12. Heagerty A. H., Fitzgerald D., Smith A., Bowers B., Jones P., Fryer A. A., Zhao L., Alldersea J., Strange R. C. Glutathione S-transferase GSTM1 phenotypes and protection against cutaneous tumours. Lancet. 1994 Jan 29;343(8892):266–268. doi: 10.1016/s0140-6736(94)91115-0. [DOI] [PubMed] [Google Scholar]
  13. Hunter D. J., Willett W. C. Diet, body build, and breast cancer. Annu Rev Nutr. 1994;14:393–418. doi: 10.1146/annurev.nu.14.070194.002141. [DOI] [PubMed] [Google Scholar]
  14. Katoh A., Watzlaf V. J., D'Amico F. An examination of obesity and breast cancer survival in post-menopausal women. Br J Cancer. 1994 Nov;70(5):928–933. doi: 10.1038/bjc.1994.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kihara M., Kihara M., Noda K. Lung cancer risk of GSTM1 null genotype is dependent on the extent of tobacco smoke exposure. Carcinogenesis. 1994 Feb;15(2):415–418. doi: 10.1093/carcin/15.2.415. [DOI] [PubMed] [Google Scholar]
  16. Lin H. J., Han C. Y., Bernstein D. A., Hsiao W., Lin B. K., Hardy S. Ethnic distribution of the glutathione transferase Mu 1-1 (GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility. Carcinogenesis. 1994 May;15(5):1077–1081. doi: 10.1093/carcin/15.5.1077. [DOI] [PubMed] [Google Scholar]
  17. Miettinen O. Estimability and estimation in case-referent studies. Am J Epidemiol. 1976 Feb;103(2):226–235. doi: 10.1093/oxfordjournals.aje.a112220. [DOI] [PubMed] [Google Scholar]
  18. Miki Y., Swensen J., Shattuck-Eidens D., Futreal P. A., Harshman K., Tavtigian S., Liu Q., Cochran C., Bennett L. M., Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994 Oct 7;266(5182):66–71. doi: 10.1126/science.7545954. [DOI] [PubMed] [Google Scholar]
  19. Moreno J. G., Croce C. M., Fischer R., Monne M., Vihko P., Mulholland S. G., Gomella L. G. Detection of hematogenous micrometastasis in patients with prostate cancer. Cancer Res. 1992 Nov 1;52(21):6110–6112. [PubMed] [Google Scholar]
  20. Nakachi K., Imai K., Hayashi S., Kawajiri K. Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res. 1993 Jul 1;53(13):2994–2999. [PubMed] [Google Scholar]
  21. Nazar-Stewart V., Motulsky A. G., Eaton D. L., White E., Hornung S. K., Leng Z. T., Stapleton P., Weiss N. S. The glutathione S-transferase mu polymorphism as a marker for susceptibility to lung carcinoma. Cancer Res. 1993 May 15;53(10 Suppl):2313–2318. [PubMed] [Google Scholar]
  22. Ollier W., Davies E., Snowden N., Alldersea J., Fryer A., Jones P., Strange R. Association of homozygosity for glutathione-S-transferase GSTM1 null alleles with the Ro+/La- autoantibody profile in patients with systemic lupus erythematosus. Arthritis Rheum. 1996 Oct;39(10):1763–1764. doi: 10.1002/art.1780391023. [DOI] [PubMed] [Google Scholar]
  23. Paradiso A., Vetrugno M. G., Capuano G., Longo S., Sibilano L., Schittulli F., Correale M., Barletta A., Pelagio G., De Lena M. Expression of GST-mu transferase in breast cancer patients and healthy controls. Int J Biol Markers. 1994 Oct-Dec;9(4):219–223. doi: 10.1177/172460089400900403. [DOI] [PubMed] [Google Scholar]
  24. Pearson W. R., Vorachek W. R., Xu S. J., Berger R., Hart I., Vannais D., Patterson D. Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet. 1993 Jul;53(1):220–233. [PMC free article] [PubMed] [Google Scholar]
  25. Phelan C. M., Rebbeck T. R., Weber B. L., Devilee P., Ruttledge M. H., Lynch H. T., Lenoir G. M., Stratton M. R., Easton D. F., Ponder B. A. Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus. Nat Genet. 1996 Mar;12(3):309–311. doi: 10.1038/ng0396-309. [DOI] [PubMed] [Google Scholar]
  26. Rebbeck T. R., Couch F. J., Kant J., Calzone K., DeShano M., Peng Y., Chen K., Garber J. E., Weber B. L. Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2. Am J Hum Genet. 1996 Sep;59(3):547–553. [PMC free article] [PubMed] [Google Scholar]
  27. Seidegård J., Pero R. W., Markowitz M. M., Roush G., Miller D. G., Beattie E. J. Isoenzyme(s) of glutathione transferase (class Mu) as a marker for the susceptibility to lung cancer: a follow up study. Carcinogenesis. 1990 Jan;11(1):33–36. doi: 10.1093/carcin/11.1.33. [DOI] [PubMed] [Google Scholar]
  28. Seidegård J., Pero R. W., Miller D. G., Beattie E. J. A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. Carcinogenesis. 1986 May;7(5):751–753. doi: 10.1093/carcin/7.5.751. [DOI] [PubMed] [Google Scholar]
  29. Seidegård J., Pero R. W. The genetic variation and the expression of human glutathione transferase mu. Klin Wochenschr. 1988;66 (Suppl 11):125–126. [PubMed] [Google Scholar]
  30. Seidegård J., Vorachek W. R., Pero R. W., Pearson W. R. 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 U S A. 1988 Oct;85(19):7293–7297. doi: 10.1073/pnas.85.19.7293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smith G., Stanley L. A., Sim E., Strange R. C., Wolf C. R. Metabolic polymorphisms and cancer susceptibility. Cancer Surv. 1995;25:27–65. [PubMed] [Google Scholar]
  32. Strange R. C., Matharoo B., Faulder G. C., Jones P., Cotton W., Elder J. B., Deakin M. The human glutathione S-transferases: a case-control study of the incidence of the GST1 0 phenotype in patients with adenocarcinoma. Carcinogenesis. 1991 Jan;12(1):25–28. doi: 10.1093/carcin/12.1.25. [DOI] [PubMed] [Google Scholar]
  33. Szabo C. I., King M. C. Population genetics of BRCA1 and BRCA2. Am J Hum Genet. 1997 May;60(5):1013–1020. [PMC free article] [PubMed] [Google Scholar]
  34. Wooster R., Bignell G., Lancaster J., Swift S., Seal S., Mangion J., Collins N., Gregory S., Gumbs C., Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995 Dec 21;378(6559):789–792. doi: 10.1038/378789a0. [DOI] [PubMed] [Google Scholar]
  35. Yengi L., Inskip A., Gilford J., Alldersea J., Bailey L., Smith A., Lear J. T., Heagerty A. H., Bowers B., Hand P. Polymorphism at the glutathione S-transferase locus GSTM3: interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma. Cancer Res. 1996 May 1;56(9):1974–1977. [PubMed] [Google Scholar]
  36. Zhong S., Wyllie A. H., Barnes D., Wolf C. R., Spurr N. K. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis. 1993 Sep;14(9):1821–1824. doi: 10.1093/carcin/14.9.1821. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES