• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. Sep 2001; 85(6): 859–862.
PMCID: PMC2375076

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

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

Full Text

The Full Text of this article is available as a PDF (60K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ackerman GE, Smith ME, Mendelson CR, MacDonald PC, Simpson ER. Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab. 1981 Aug;53(2):412–417. [PubMed]
  • Bergman-Jungeström M, Gentile M, Lundin AC, 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. [PubMed]
  • Bonnier P, Romain S, Charpin C, Lejeune C, Tubiana N, Martin PM, 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. [PubMed]
  • Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, Johansson SL, Patil KD, Gross ML, Gooden JK, et al. 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. [PMC free article] [PubMed]
  • Dreher D, Junod AF. Role of oxygen free radicals in cancer development. Eur J Cancer. 1996 Jan;32A(1):30–38. [PubMed]
  • Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP, Schweigerer L. The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature. 1994 Mar 17;368(6468):237–239. [PubMed]
  • Harris JR, Lippman ME, Veronesi U, Willett W. Breast cancer (1) N Engl J Med. 1992 Jul 30;327(5):319–328. [PubMed]
  • Huang CS, Chern HD, Chang KJ, Cheng CW, Hsu SM, Shen CY. 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]
  • Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996 Jun;6(3):243–250. [PubMed]
  • Lavigne JA, Helzlsouer KJ, Huang HY, Strickland PT, Bell DA, Selmin O, Watson MA, Hoffman S, Comstock GW, Yager JD. 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]
  • Li SA, Purdy RH, Li JJ. Variations in catechol O-methyltransferase activity in rodent tissues: possible role in estrogen carcinogenicity. Carcinogenesis. 1989 Jan;10(1):63–67. [PubMed]
  • Liehr JG. 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. [PubMed]
  • Liehr JG, Ricci MJ. 4-Hydroxylation of estrogens as marker of human mammary tumors. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3294–3296. [PMC free article] [PubMed]
  • Lundin AC, 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]
  • Magnusson C, Baron J, Persson I, Wolk A, Bergström R, Trichopoulos D, Adami HO. 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. [PubMed]
  • Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000 Mar;21(3):361–370. [PubMed]
  • Millikan RC, Pittman GS, Tse CK, Duell E, Newman B, Savitz D, Moorman PG, Boissy RJ, Bell DA. Catechol-O-methyltransferase and breast cancer risk. Carcinogenesis. 1998 Nov;19(11):1943–1947. [PubMed]
  • Nixon AJ, Neuberg D, Hayes DF, Gelman R, Connolly JL, Schnitt S, Abner A, Recht A, Vicini F, Harris JR. 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. [PubMed]
  • Scanlon PD, Raymond FA, Weinshilboum RM. Catechol-O-methyltransferase: thermolabile enzyme in erythrocytes of subjects homozygous for allele for low activity. Science. 1979 Jan 5;203(4375):63–65. [PubMed]
  • Spurdle AB, Hopper JL, Dite GS, Chen X, Cui J, McCredie MR, Giles GG, Southey MC, Venter DJ, Easton DF, et al. CYP17 promoter polymorphism and breast cancer in Australian women under age forty years. J Natl Cancer Inst. 2000 Oct 18;92(20):1674–1681. [PubMed]
  • Taioli E, Trachman J, Chen X, Toniolo P, Garte SJ. 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]
  • Thompson PA, Shields PG, Freudenheim JL, Stone A, Vena JE, Marshall JR, Graham S, Laughlin R, Nemoto T, Kadlubar FF, et al. Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk. Cancer Res. 1998 May 15;58(10):2107–2110. [PubMed]
  • van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, Fraser G, Goldbohm RA, Graham S, Kushi L, et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000 Sep 15;152(6):514–527. [PubMed]
  • Weber BL, Nathanson KL. Low penetrance genes associated with increased risk for breast cancer. Eur J Cancer. 2000 Jun;36(10):1193–1199. [PubMed]
  • Yager JD, Liehr JG. Molecular mechanisms of estrogen carcinogenesis. Annu Rev Pharmacol Toxicol. 1996;36:203–232. [PubMed]
  • Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis. 1993 Sep;14(9):1821–1824. [PubMed]
  • Zhu BT, Conney AH. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998 Jan;19(1):1–27. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...