Leiden University Scholarly Publications

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Hilbers, F.S.M. (2020)

The genetic etiology of familial breast cancer: Assessing the role of rare genetic variation using next generation sequencing

Doctoral Thesis
A family history of breast cancer is one of the most important risk factors for the disease. Over the last decades many genetic loci associated with breast cancer risk have been discovered. In spite of this, only approximately half of the familial relative risk (FRR) for breast cancer can be explained by the currently known genetic risk factor. In this thesis we have explored the role of rare genetic variants in familial breast cancer with the help of next generation sequencing. Through this approach we have not been able to identify any novel high-risk breast cancer susceptibility alleles. Although there are likely still several extremely rare risk alleles to be discovered and the presence of high-risk alleles outside of protein-coding regions cannot be excluded, it seems presently unlikely that these will explain a substantial proportion of familial breast cancer. Both our work and that of others has suggested that most non BRCA1/2 familial breast cancer cases are likely...Show moreA family history of breast cancer is one of the most important risk factors for the disease. Over the last decades many genetic loci associated with breast cancer risk have been discovered. In spite of this, only approximately half of the familial relative risk (FRR) for breast cancer can be explained by the currently known genetic risk factor. In this thesis we have explored the role of rare genetic variants in familial breast cancer with the help of next generation sequencing. Through this approach we have not been able to identify any novel high-risk breast cancer susceptibility alleles. Although there are likely still several extremely rare risk alleles to be discovered and the presence of high-risk alleles outside of protein-coding regions cannot be excluded, it seems presently unlikely that these will explain a substantial proportion of familial breast cancer. Both our work and that of others has suggested that most non BRCA1/2 familial breast cancer cases are likely explained by a combination of low-, and moderate-risk susceptibility alleles.
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Breast Cancer
Hereditary
Familial
Next-generation sequencing (NGS)
Risk
Predisposition
Functional analysis
All authors
Hilbers, F.S.M.
Supervisor
Devilee, P.; Asperen, C.J. van
Committee
Attikum, H. van; Morreau, J.; Mensenkamp, A.R.; Rookus, M.A.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center [LUMC], Leiden University
Date
2020-07-07
ISBN (print)
9789083070421

Funding

Sponsorship
The work presented in this thesis was financially supported by the Dutch Cancer Society (grant UL 2009-4388).