| Title: | Breast and prostate cancer risk: The interplay of polygenic risk, rare pathogenic germline variants, and family history |
| Journal: | Genetics in Medicine |
| Published: | 18 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34906469/ |
| DOI: | https://doi.org/10.1016/j.gim.2021.11.009 |
| Citations: | 27 (18 in last 2 years) as of 8 Aug 2024 |
Publication 12658
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Abstract
PURPOSE: We aimed to investigate to what extent polygenic risk scores (PRS), rare pathogenic germline variants (PVs), and family history jointly influence breast cancer and prostate cancer risk.</p>
METHODS: A total of 200,643 individuals from the UK Biobank were categorized as follows: (1) heterozygotes or nonheterozygotes for PVs in moderate to high-risk cancer genes, (2) PRS strata, and (3) with or without a family history of cancer. Multivariable logistic regression and Cox proportional hazards models were used to compute the odds ratio across groups and the cumulative incidence through life.</p>
RESULTS: Cumulative incidence by age 70 years among the nonheterozygotes across PRS strata ranged from 9% to 32% and from 9% to 35% for breast cancer and prostate cancer, respectively. Among the PV heterozygotes it ranged from 20% to 48% in moderate-risk genes and from 51% to 74% in high-risk genes for breast cancer, and it ranged from 30% to 59% in prostate cancer risk genes. Family history was always associated with an increased cancer odds ratio.</p>
CONCLUSION: PRS alone provides a meaningful risk gradient leading to a cancer risk stratification comparable to PVs in moderate risk genes, whereas acts as a risk modifier when considering high-risk genes. Including family history along with PV and PRS further improves cancer risk stratification.</p>
9 Keywords
- Aged
- Breast Neoplasms
- Genetic Predisposition to Disease
- Germ Cells
- Humans
- Male
- Multifactorial Inheritance
- Prostatic Neoplasms
- Risk Factors
10 Authors
- Emadeldin Hassanin
- Patrick May
- Rana Aldisi
- Isabel Spier
- Andreas J Forstner
- Markus M Nöthen
- Stefan Aretz
- Peter Krawitz
- Dheeraj Reddy Bobbili
- Carlo Maj
1 Application
| Application ID | Title |
|---|---|
| 52446 | Predictive and integrative models for disease prevention using the UK Biobank Data |
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