Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Catechol-O-Methyltransferase (COMT) gene polymorphism and breast cancer risk in young women
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 11 September 2001

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

  • M Bergman-Jungeström1 &
  • S Wingren1 

British Journal of Cancer volume 85, pages 859–862 (2001)Cite this article

  • 1841 Accesses

  • 52 Citations

  • Metrics details

This article has been updated

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 Campaign http://www.bjcancer.com

Similar content being viewed by others

Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer

Article Open access 23 January 2023

Phase II trial of delta-tocotrienol in neoadjuvant breast cancer with evaluation of treatment response using ctDNA

Article Open access 24 May 2023

Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer

Article Open access 09 September 2021

Article PDF

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Ackerman GE, Smith ME, Mendelson CR, MacDonald PC and Simpson ER (1981) Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin & Metab 53: 412–417

    Article  CAS  Google Scholar 

  • Bergman-Jungeström M, Gentile M, Lundin AC & the South-east breast cancer group Wingren S (1999) Association between CYP17 gene polymorphism and risk of breast cancer in young women. Int J Cancer (Pred Oncol) 84: 350–353

    Article  Google Scholar 

  • Bonnier P, Romain S, Charpin C, Lejeune C, Tubiana N, Martin PM and Piana L (1995) Age as a prognostic factor in breast cancer: relationship to pathology and biological features. Int J Cancer 62: 138–144

    Article  CAS  Google Scholar 

  • Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, Johansson SL, Patil KD, Gross ML, Gooden JK, Ramanathan RL and Rogan EG (1997) Molecular origin of cancer: Catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Natl Acad Sci 94: 10937–10942

    Article  CAS  Google Scholar 

  • Dreher D and Junod AF (1996) Role of oxygen free radicals in cancer development. Eur J Cancer 32A: 30–38

    Article  CAS  Google Scholar 

  • Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP and Schweigerer L (1994) The endogenous oestrogen metabolite 2-methoxyoetradiol inhibits angiogenesis and suppresses tumour growth. Nature 368: 237–239

    Article  CAS  Google Scholar 

  • Harris JR, Lippman ME, Veronesi U and Willett W (1992) Breast cancer. N Engl J Med 327: 319–328

    Article  CAS  Google Scholar 

  • Huang CS, Chern HD, Chang KJ, Cheng CW, Hsu SM and Shen CY (1999) Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59: 4870–4875

    CAS  PubMed  Google Scholar 

  • Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL and Weinshilboum RM (1996) Human catechol-o-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6: 243–250

    Article  CAS  Google Scholar 

  • Lavigne JA, Helzlsouer KJ, Huang HY, Strickland PT, Bell DA, Selmin O, Watson MA, Hoffman S, Comstock GW and Yager JD (1997) An Association between the allele coding for a low activity variant of catechol-o-methyltransferase and the risk for breast cancer. Cancer Res 57: 5493–5497

    CAS  PubMed  Google Scholar 

  • Li SA, Purdy RH and Li JJ (1989) Variations in catechol O-methyltransferase activity in rodent tissues: possible role in estrogen carcinogenicity. Carcinogenesis 10: 63–67

    Article  CAS  Google Scholar 

  • Liehr JG (1997) Dual role of oestrogens as hormones and pro-carcinogens: tumour initiation by metabolic activation of oestrogens. Eur J Cancer Prev 6: 3–10

    Article  CAS  Google Scholar 

  • Liehr JG and Ricci MJ (1996) 4-Hydroxylation of estrogens as marker of human mammary tumors. Proc Natl Acad Sci 93: 3294–3296

    Article  CAS  Google Scholar 

  • Lundin AC, Söderkvist P, Eriksson B, Bergman-Jungeström M and Wingren S the south-east Sweden Breast Cancer Group (1999) Association of breast cancer progression with a vitamin D receptor gene polymorphism. Cancer Res 59: 2332–2334

    CAS  PubMed  Google Scholar 

  • Magnusson C, Baron J, Persson I, Wolk A, Bergström R, Trichopoulos, and Adami H-O (1998) Body size in different periods of life and breast cancer risk in post-menopausal women. Int J Cancer 76: 29–34

    Article  CAS  Google Scholar 

  • Marnett LJ (2000) Oxyradicals and DNA damage. Carcinogenesis 21: 361–370

    Article  CAS  Google Scholar 

  • Millikan RC, Pittman GS, Tse CKJ, Duell E, Newman B, Savitz D, Moorman PG, Boissy RJ and Bell DA (1998) Catechol-o-methyltransferase and breast cancer risk. Carcinogenesis 19: 1943–1947

    Article  CAS  Google Scholar 

  • Nixon AJ, Neuberg D, Hayes DF, Gelman R, Connolly JL, Schnitt S, Abner A, Recht A, Vicini F and Harris JR (1994) Relationship of patient age to pathologic feature of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol 12: 888–894

    Article  CAS  Google Scholar 

  • Scanlon PD, Raymond FA and Weinshilboum RM (1979) Catechol-O-methyltransferase: thermolabile enzyme in erythrocytes of subjects homozygous for allele for low activity. Science 5: 63–65

    Article  Google Scholar 

  • Sprudle AB, Hopper JL, Dite GS, Chen X, Cui J, McCredie MRE, Giles GG, Southey MC, Venter DJ, Easton DF and Chenevix-Trench G (2000) CYP17 promoter polymorphism and breast cancer in Australian women under age forty years. J Nat Cancer Inst 92: 1674–1681

    Article  Google Scholar 

  • Taioli E, Trachman J, Chen X, Toniolo P and Garte SJ (1995) A CYP1A1 Restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res 55: 3757–3758

    CAS  PubMed  Google Scholar 

  • Thompson PA, Shields PG, Freudenheim JL, Stone A, Vena JE, Marshall JR, Graham S, Laughlin R, Nemoto T, Kadlubar FF and Ambrosone CB (1998) Genetic polymorphism in catechol-o-methyltransferase, menopausal status and breast cancer risk. Cancer Res 58: 2107–2110

    CAS  PubMed  Google Scholar 

  • van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, Fraser G, Goldbohm RA, Graham S, Kushi L, Marshall JR, Miller AB, Rohan T, Smith-Warner SA, Speizer FE, Willett WC, Wolk A and Hunter DJ (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 15: 514–527

    Article  Google Scholar 

  • Weber BL and Nathanson KL (2000) Low penetrance genes associated with increased risk for breast cancer. Eur J Cancer 36: 1193–1199

    Article  CAS  Google Scholar 

  • Weisz J (1994) Biogenesis of catecholestrogens: A mechanism for metabolic activation of estrogens. Polycyclic Aromatic Compounds 6: 241–251

    Article  CAS  Google Scholar 

  • Yager JD and Liehr JG (1996) Molecular mechanisms of estrogen carcinogenesis. Annu Rev Pharmacol Toxicol 36: 203–232

    Article  CAS  Google Scholar 

  • Zhong S, Wyllie AH, Barnes D, Wolf CR and Spurr NK (1993) Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14: 1821–1824

    Article  CAS  Google Scholar 

  • Zhu BT and Conney AH (1998) Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis 19: 1–27

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, University Hospital, Linköping, S-581 85, Sweden

    M Bergman-Jungeström & S Wingren

Authors
  1. M Bergman-Jungeström
    View author publications

    Search author on:PubMed Google Scholar

  2. S Wingren
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and permissions

About this article

Cite this article

Bergman-Jungeström, M., Wingren, S. Catechol-O-Methyltransferase (COMT) gene polymorphism and breast cancer risk in young women. Br J Cancer 85, 859–862 (2001). https://doi.org/10.1054/bjoc.2001.2009

Download citation

  • Received: 16 February 2001

  • Revised: 20 June 2001

  • Accepted: 02 July 2001

  • Published: 11 September 2001

  • Issue date: 14 September 2001

  • DOI: https://doi.org/10.1054/bjoc.2001.2009

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Catechol-O-Methyltransferase
  • COMT
  • genetic polymorphism
  • breast cancer
  • early onset
  • catechol oestrogens

This article is cited by

  • The association of genetic polymorphisms with neuroconnectivity in breast cancer patients

    • Rebecca A. Harrison
    • Vikram Rao
    • Shelli R. Kesler

    Scientific Reports (2021)

  • Catechol-O-methyltransferase Val 108/158 Met polymorphism and breast cancer risk: a case control study in Syria

    • Bassam Lajin
    • Abdul Rezzak Hamzeh
    • Amal Alachkar

    Breast Cancer (2013)

  • Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis

    • Xue Qin
    • Qiliu Peng
    • Jinmin Zhao

    Diagnostic Pathology (2012)

  • Association between the COMT Val158Met polymorphism and breast cancer risk: a meta-analysis of 30,199 cases and 38,922 controls

    • Xiao-Feng He
    • Wu Wei
    • Wei Wang

    Molecular Biology Reports (2012)

  • Catechol-O-methyltransferase Val158Met polymorphism in breast cancer risk

    • Bo Xi
    • Tao Zeng
    • Weina Liu

    Breast Cancer Research and Treatment (2011)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited