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Interactions between a Polygenic Risk Score and Non-genetic Risk Factors in Young-Onset Breast Cancer.

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  • 1Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States.

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|February 26, 2020
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Summary
This summary is machine-generated.

Genetic risk scores interact with lifestyle factors to influence young-onset breast cancer (YOBC) risk. Hormonal birth control use and menopausal status modify the association between polygenic risk scores (PRS) and YOBC.

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Area of Science:

  • Genetics and Epidemiology
  • Oncology
  • Environmental Health

Background:

  • Young-onset breast cancer (YOBC) often presents aggressively and may have distinct etiological factors compared to later-onset disease.
  • Gene-environment interactions are crucial for understanding breast cancer development, particularly in younger populations.
  • Established polygenic risk scores (PRS) can quantify genetic predisposition to breast cancer.

Purpose of the Study:

  • To investigate potential interactions between a 77-SNP polygenic risk score (PRS) and non-genetic risk factors specific to young-onset breast cancer (YOBC).
  • To assess how established risk factors modify the association between genetic predisposition and YOBC risk.

Main Methods:

  • A family-based study cohort of 1,291 women diagnosed with breast cancer before age 50 was used to construct a 77-SNP PRS.
  • Conditional logistic regression analyzed interactions between the PRS and 14 established risk factors.
  • Analyses were further stratified by cancer invasiveness, estrogen receptor (ER) status, and racial/ethnic groups.

Main Results:

  • A significant interaction was observed between the PRS and hormonal birth control use, showing a decreased association with YOBC risk in users (OR=2.20 vs. 3.89).
  • The PRS demonstrated a stronger association with YOBC risk in pre-menopausal women (OR=2.46 vs. 1.23).
  • Similar interaction patterns were maintained when analyses were restricted to invasive cancers, ER-positive cancers, or included broader ethnic groups.

Conclusions:

  • The polygenic risk score (PRS) may interact with hormonal birth control use, potentially mitigating genetic risk for young-onset breast cancer (YOBC).
  • Menopausal status significantly influences the association between PRS and YOBC risk, with a stronger effect observed in pre-menopausal women.
  • These findings highlight the importance of considering gene-environment interactions in personalized risk assessment for YOBC.