IDEAS home Printed from https://ideas.repec.org/a/wly/riskan/v11y1991i3p483-490.html
   My bibliography  Save this article

Additive and Multiplicative Relative Risk in the Two‐Stage Clonal Expansion Model of Carcinogenesis

Author

Listed:
  • Ralph L. Kodell
  • Daniel Krewski
  • Jan M. Zielinski

Abstract

The effects of exposure to two carcinogens are explored within the context of the two‐stage clonal expansion model of carcinogenesis. This biologically based model provides a useful framework for the quantitative description of carcinogenesis, and for defining carcinogenic agents that act as initiators, promoters, and completers. This paper addresses the combined effects of simultaneous lifetime exposure to two carcinogens as well as nonoverlapping partial lifetime exposure to each agent. Whereas the age‐specific relative risk for exposure to two initiators or two completers is additive, a multiplicative relative risk model holds for exposure to an initiator and a completer, or to a promoter and a completer. Exposure to two promoters yields supra‐multiplicative relative risk. Exposure to an initiator and promoter leads to multiplicative and supra‐multiplicative relative risks for simultaneous lifetime and nonoverlapping partial lifetime exposures, respectively. Although departures from the additive relative risk model may thus occur at moderate to high doses, conditions are identified under which additivity will provide a good approximation to the joint risk at low doses. The methods of analysis used in this paper can also be used to determine the joint effects of exposure to two carcinogens which may affect more than one stage (initiation, promotion, completion) of the process of carcinogenesis. In general, the joint effects of exposure to such agents depends on the relative magnitude of the effects on individual stages.

Suggested Citation

  • Ralph L. Kodell & Daniel Krewski & Jan M. Zielinski, 1991. "Additive and Multiplicative Relative Risk in the Two‐Stage Clonal Expansion Model of Carcinogenesis," Risk Analysis, John Wiley & Sons, vol. 11(3), pages 483-490, September.
    • Handle: RePEc:wly:riskan:v:11:y:1991:i:3:p:483-490
    DOI: 10.1111/j.1539-6924.1991.tb00633.x
    as

    Download full text from publisher

    File URL: https://doi.org/10.1111/j.1539-6924.1991.tb00633.x
    Download Restriction: no
    File URL: https://libkey.io/10.1111/j.1539-6924.1991.tb00633.x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. James J. Chen & David W. Gaylor & Ralph L. Kodell, 1990. "Estimation of the Joint Risk from Multiple‐Compound Exposure Based on Single‐Compound Experiments," Risk Analysis, John Wiley & Sons, vol. 10(2), pages 285-290, June.
    2. Herman J. Gibb & Chao W. Chen, 1986. "Multistage Model Interpretation of Additive and Multiplicative Carcinogenic Effects," Risk Analysis, John Wiley & Sons, vol. 6(2), pages 167-170, June.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Chao W. Chen, 1993. "Armitage‐Doll Two‐Stage Model: Implications and Extension," Risk Analysis, John Wiley & Sons, vol. 13(3), pages 273-279, June.
    2. Daniel Krewski & Richard D. Thomas, 1992. "Carcinogenic Mixtures," Risk Analysis, John Wiley & Sons, vol. 12(1), pages 105-113, March.
    3. David W. Gaylor & James J. Chen, 1996. "A Simple Upper Limit for the Sum of the Risks of the Components in a Mixture," Risk Analysis, John Wiley & Sons, vol. 16(3), pages 395-398, June.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. David W. Gaylor & James J. Chen, 1996. "A Simple Upper Limit for the Sum of the Risks of the Components in a Mixture," Risk Analysis, John Wiley & Sons, vol. 16(3), pages 395-398, June.
    2. Vincent James Cogliano, 1997. "Plausible Upper Bounds: Are Their Sums Plausible?," Risk Analysis, John Wiley & Sons, vol. 17(1), pages 77-84, February.
    3. Jing‐Shiang Hwang & James J. Chen, 1999. "An Evaluation of Risk Estimation Procedures for Mixtures of Carcinogens," Risk Analysis, John Wiley & Sons, vol. 19(6), pages 1071-1076, December.
    4. Sati Mazumdar & Carol K. Redmond & Philip E. Enterline & Gary M. Marsh & Joseph P. Costantino & Susan Y. J. Zhou & Rita N. Patwardhan, 1989. "Multistage Modeling of Lung Cancer Mortality Among Arsenic‐Exposed Copper‐Smelter Workers," Risk Analysis, John Wiley & Sons, vol. 9(4), pages 551-563, December.
    5. T. R. Auton, 1991. "Joint Risk from Multiple Compound Exposure," Risk Analysis, John Wiley & Sons, vol. 11(2), pages 181-183, June.
    6. Charles C. Brown & Kenneth C. Chu, 1989. "Additive and Multiplicative Models and Multistage Carcinogenesis Theory," Risk Analysis, John Wiley & Sons, vol. 9(1), pages 99-105, March.
    7. James J. Chen & David W. Gaylor & Ralph L. Kodell, 1990. "Estimation of the Joint Risk from Multiple‐Compound Exposure Based on Single‐Compound Experiments," Risk Analysis, John Wiley & Sons, vol. 10(2), pages 285-290, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:wly:riskan:v:11:y:1991:i:3:p:483-490. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Wiley Content Delivery (email available below). General contact details of provider: https://doi.org/10.1111/(ISSN)1539-6924 .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.