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Article
Wei Zheng
Vanderbilt University Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1226-070X
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This work is licensed under a CC BY 4.0 License. Read Full License
Structural deletions in breast cancer susceptibility genes could confer to cancer risk, but remain poorly characterized. Here, we conducted in-depth whole genome sequencing (WGS) in germline DNA samples from 1,340 invasive breast cancer cases and 675 controls of African ancestry to discover such deletions. We identified 33 deletions, including five protein-truncating deletions in BRCA1, BRCA2, RAD51C, GEN1, and BRIP1, were observed only in cases but not in controls. Three deletions, including one protein-truncating deletion in TP53, were found to have a higher frequency in cases than in controls. In total, 4.6% of cases and 0.6% of controls carried any of these 36 deletions, resulting in an odds ratio (OR) of 8.0 (95%CI = 2.94 - 30.41). In addition, we identified a low-frequency deletion in NF1 associated with breast cancer risk (OR = 1.93, 95%CI = 1.14 - 3.42). These findings have significant implications for genetic testing for this common cancer.
Keywords
breast cancer, cancer, BRCA1, BRCA2
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This is a list of supplementary files associated with this preprint. Click to download.
- Supplementarydata.xlsx
Supplementary Data 1-7 Supplementary Data 1: Clinical data of study participants by studies. Supplementary Data 2: Parameters for each SV caller used in this study. Supplementary Data 3: List of 40 breast cancer susceptibility genes included in this study. Supplementary Data 4: List of 80 potential loss-of-function deletions identified in breast cancer susceptibility genes. Supplementary Data 5: Characterization of 37 reported potential loss-of-function deletions. Supplementary Data 6: Distribution of carriers of any one of the 37 reported potential loss-of-function deletions by participating studies. Supplementary Data 7: List of potential loss-of-function deletions identified with high reciprocal overlap (>90%) with deletions in gnomAD.
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This is a preprint. It has not completed peer review.
Article
Wei Zheng
Vanderbilt University Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1226-070X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 10 Aug, 2020
No community comments so far
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Structural deletions in breast cancer susceptibility genes could confer to cancer risk, but remain poorly characterized. Here, we conducted in-depth whole genome sequencing (WGS) in germline DNA samples from 1,340 invasive breast cancer cases and 675 controls of African ancestry to discover such deletions. We identified 33 deletions, including five protein-truncating deletions in BRCA1, BRCA2, RAD51C, GEN1, and BRIP1, were observed only in cases but not in controls. Three deletions, including one protein-truncating deletion in TP53, were found to have a higher frequency in cases than in controls. In total, 4.6% of cases and 0.6% of controls carried any of these 36 deletions, resulting in an odds ratio (OR) of 8.0 (95%CI = 2.94 - 30.41). In addition, we identified a low-frequency deletion in NF1 associated with breast cancer risk (OR = 1.93, 95%CI = 1.14 - 3.42). These findings have significant implications for genetic testing for this common cancer.
Figure 1
Figure 2
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