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A framework for assessing interactions for risk stratification models: the example of ovarian cancer

  • Australian Ovarian Cancer Study Group
  • , Ovarian Cancer Association Consortium
  • University of Michigan, Ann Arbor
  • California State University Fullerton
  • Roswell Park Cancer Institute
  • University of California at Irvine
  • Rutgers - The State University of New Jersey, New Brunswick
  • University of Hawai'i at Mānoa
  • German Cancer Research Center
  • University of Hamburg
  • Harvard University
  • University of Utah
  • Cancer Registry of Norway Institute of Population-Based Cancer Research
  • Cedars-Sinai Medical Center
  • Fred Hutchinson Cancer Research Center
  • University of Washington
  • Danish Cancer Society
  • University of Pittsburgh
  • University of Southern Maine
  • Queensland Institute of Medical Research
  • University of Southern California
  • Duke University
  • University of British Columbia
  • Provincial Health Services Authority
  • Memorial Sloan-Kettering Cancer Center

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.

Original languageEnglish
Pages (from-to)1420-1426
Number of pages7
JournalJournal of the National Cancer Institute
Volume115
Issue number11
DOIs
StatePublished - Nov 1 2023

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