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. 2001 Sep;85(6):859–862. doi: 10.1054/bjoc.2001.2009

Catechol-O-Methyltransferase (COMT) gene polymorphism and breast cancer risk in young women

M Bergman-Jungeström 1, S Wingren 1
PMCID: PMC2375076  PMID: 11556837

Abstract

Oestrogen exposure has long been considered to be a main risk factor of breast cancer. More recently, interest has also focused on the possible carcinogenic influence from oestrogen metabolites, such as catechol oestrogens. O-methylation, catalysed by Catechol-O-Methyltransferase (COMT), is one pathway by which the potentially carcinogenic catechol oestrogens can be inactivated. The gene coding for COMT protein contains a single-nucleotide polymorphism (SNP), resulting in an amino acid shift Val→Met, which has been shown to determine high- and low-activity configuration of the enzyme. We hypothesized that the low-activity allele, COMTMet, may be implicated in early onset breast cancer. In the present case–control study, including 126 young breast cancer patients (≤ 36 years) and 117 healthy female blood donors, we analysed the association between COMTMet genotype and risk of breast cancer. No significant difference in the frequency of low-/high-activity alleles was found between cases and controls, indicating that the polymorphism, as a single factor, may not contribute to breast carcinogenesis in young women. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

Keywords: Catechol-O-Methyltransferase, COMT, genetic polymorphism, breast cancer, early onset, catechol oestrogens

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Selected References

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  1. Ackerman G. E., Smith M. E., Mendelson C. R., MacDonald P. C., Simpson E. R. Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab. 1981 Aug;53(2):412–417. doi: 10.1210/jcem-53-2-412. [DOI] [PubMed] [Google Scholar]
  2. Bergman-Jungeström M., Gentile M., Lundin A. C., Wingren S. Association between CYP17 gene polymorphism and risk of breast cancer in young women. Int J Cancer. 1999 Aug 20;84(4):350–353. doi: 10.1002/(sici)1097-0215(19990820)84:4<350::aid-ijc3>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  3. Bonnier P., Romain S., Charpin C., Lejeune C., Tubiana N., Martin P. M., Piana L. Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features. Int J Cancer. 1995 Jul 17;62(2):138–144. doi: 10.1002/ijc.2910620205. [DOI] [PubMed] [Google Scholar]
  4. Cavalieri E. L., Stack D. E., Devanesan P. D., Todorovic R., Dwivedy I., Higginbotham S., Johansson S. L., Patil K. D., Gross M. L., Gooden J. K. Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937–10942. doi: 10.1073/pnas.94.20.10937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dreher D., Junod A. F. Role of oxygen free radicals in cancer development. Eur J Cancer. 1996 Jan;32A(1):30–38. doi: 10.1016/0959-8049(95)00531-5. [DOI] [PubMed] [Google Scholar]
  6. Fotsis T., Zhang Y., Pepper M. S., Adlercreutz H., Montesano R., Nawroth P. P., Schweigerer L. The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature. 1994 Mar 17;368(6468):237–239. doi: 10.1038/368237a0. [DOI] [PubMed] [Google Scholar]
  7. Harris J. R., Lippman M. E., Veronesi U., Willett W. Breast cancer (1) N Engl J Med. 1992 Jul 30;327(5):319–328. doi: 10.1056/NEJM199207303270505. [DOI] [PubMed] [Google Scholar]
  8. Huang C. S., Chern H. D., Chang K. J., Cheng C. W., Hsu S. M., Shen C. Y. Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res. 1999 Oct 1;59(19):4870–4875. [PubMed] [Google Scholar]
  9. Lachman H. M., Papolos D. F., Saito T., Yu Y. M., Szumlanski C. L., Weinshilboum R. M. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996 Jun;6(3):243–250. doi: 10.1097/00008571-199606000-00007. [DOI] [PubMed] [Google Scholar]
  10. Lavigne J. A., Helzlsouer K. J., Huang H. Y., Strickland P. T., Bell D. A., Selmin O., Watson M. A., Hoffman S., Comstock G. W., Yager J. D. An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. Cancer Res. 1997 Dec 15;57(24):5493–5497. [PubMed] [Google Scholar]
  11. Li S. A., Purdy R. H., Li J. J. Variations in catechol O-methyltransferase activity in rodent tissues: possible role in estrogen carcinogenicity. Carcinogenesis. 1989 Jan;10(1):63–67. doi: 10.1093/carcin/10.1.63. [DOI] [PubMed] [Google Scholar]
  12. Liehr J. G. Dual role of oestrogens as hormones and pro-carcinogens: tumour initiation by metabolic activation of oestrogens. Eur J Cancer Prev. 1997 Feb;6(1):3–10. doi: 10.1097/00008469-199702000-00002. [DOI] [PubMed] [Google Scholar]
  13. Liehr J. G., Ricci M. J. 4-Hydroxylation of estrogens as marker of human mammary tumors. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3294–3296. doi: 10.1073/pnas.93.8.3294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lundin A. C., Söderkvist P., Eriksson B., Bergman-Jungeström M., Wingren S. Association of breast cancer progression with a vitamin D receptor gene polymorphism. South-East Sweden Breast Cancer Group. Cancer Res. 1999 May 15;59(10):2332–2334. [PubMed] [Google Scholar]
  15. Magnusson C., Baron J., Persson I., Wolk A., Bergström R., Trichopoulos D., Adami H. O. Body size in different periods of life and breast cancer risk in post-menopausal women. Int J Cancer. 1998 Mar 30;76(1):29–34. doi: 10.1002/(sici)1097-0215(19980330)76:1<29::aid-ijc6>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  16. Marnett L. J. Oxyradicals and DNA damage. Carcinogenesis. 2000 Mar;21(3):361–370. doi: 10.1093/carcin/21.3.361. [DOI] [PubMed] [Google Scholar]
  17. Millikan R. C., Pittman G. S., Tse C. K., Duell E., Newman B., Savitz D., Moorman P. G., Boissy R. J., Bell D. A. Catechol-O-methyltransferase and breast cancer risk. Carcinogenesis. 1998 Nov;19(11):1943–1947. doi: 10.1093/carcin/19.11.1943. [DOI] [PubMed] [Google Scholar]
  18. Nixon A. J., Neuberg D., Hayes D. F., Gelman R., Connolly J. L., Schnitt S., Abner A., Recht A., Vicini F., Harris J. R. Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol. 1994 May;12(5):888–894. doi: 10.1200/JCO.1994.12.5.888. [DOI] [PubMed] [Google Scholar]
  19. Scanlon P. D., Raymond F. A., Weinshilboum R. M. Catechol-O-methyltransferase: thermolabile enzyme in erythrocytes of subjects homozygous for allele for low activity. Science. 1979 Jan 5;203(4375):63–65. doi: 10.1126/science.758679. [DOI] [PubMed] [Google Scholar]
  20. Spurdle A. B., Hopper J. L., Dite G. S., Chen X., Cui J., McCredie M. R., Giles G. G., Southey M. C., Venter D. J., Easton D. F. CYP17 promoter polymorphism and breast cancer in Australian women under age forty years. J Natl Cancer Inst. 2000 Oct 18;92(20):1674–1681. doi: 10.1093/jnci/92.20.1674. [DOI] [PubMed] [Google Scholar]
  21. Taioli E., Trachman J., Chen X., Toniolo P., Garte S. J. A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res. 1995 Sep 1;55(17):3757–3758. [PubMed] [Google Scholar]
  22. Thompson P. A., Shields P. G., Freudenheim J. L., Stone A., Vena J. E., Marshall J. R., Graham S., Laughlin R., Nemoto T., Kadlubar F. F. Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk. Cancer Res. 1998 May 15;58(10):2107–2110. [PubMed] [Google Scholar]
  23. Weber B. L., Nathanson K. L. Low penetrance genes associated with increased risk for breast cancer. Eur J Cancer. 2000 Jun;36(10):1193–1199. doi: 10.1016/s0959-8049(00)00082-4. [DOI] [PubMed] [Google Scholar]
  24. Yager J. D., Liehr J. G. Molecular mechanisms of estrogen carcinogenesis. Annu Rev Pharmacol Toxicol. 1996;36:203–232. doi: 10.1146/annurev.pa.36.040196.001223. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Zhu B. T., Conney A. H. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998 Jan;19(1):1–27. doi: 10.1093/carcin/19.1.1. [DOI] [PubMed] [Google Scholar]
  27. van den Brandt P. A., Spiegelman D., Yaun S. S., Adami H. O., Beeson L., Folsom A. R., Fraser G., Goldbohm R. A., Graham S., Kushi L. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000 Sep 15;152(6):514–527. doi: 10.1093/aje/152.6.514. [DOI] [PubMed] [Google Scholar]

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