Combined associations of a polygenic risk score and classical risk factors with breast cancer risk

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72,284 cases and 80,354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression, and a newly developed case-only method, for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history), and on average 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

Detaljer

Författare
  • ABCTB Investigators
Externa organisationer
  • Heidelberg University
  • University of Cambridge
  • University of Washington, Seattle
  • Fred Hutchinson Cancer Research Center
  • German Cancer Research Centre
  • Carmel Medical Center
  • University of Toronto
  • University of California, Irvine
  • University of Wisconsin-Milwaukee
  • Spanish National Cancer Research Center (CNIO)
  • Beckman Research Institute of City of Hope
  • University of Copenhagen
  • University of Pisa
  • Johns Hopkins University
  • QIMR Berghofer Medical Research Institute
  • University of Sydney
  • Mayo Clinic Minnesota
  • University of Sheffield
  • Karolinska Institute
  • University of North Carolina
  • Harvard T.H. Chan School of Public Health
  • University of California, Los Angeles
  • National Cancer Institute
  • Cyprus Institute of Neurology and Genetics
  • National Cancer Institute, NCI
  • Queen's University
  • Charité Universitätsmedizin Berlin
  • University Hospital Erlangen
  • Vanderbilt University School of Medicine
  • Ruhr-University Bochum
  • CIBER de Enfermedades Raras (CIBERER)
  • University of Santiago de Compostela
  • American Cancer Society
  • Xerencia de Xestion Integrada de Vigo-SERGAS
  • St. Mary’s Hospital, Manchester
  • Södersjukhuset
  • Leiden University Medical Centre
  • University Medical Center Hamburg-Eppendorf
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
Originalspråkengelska
TidskriftJournal of the National Cancer Institute
StatusE-pub ahead of print - 2020 maj 2
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa