Two truncating variants in FANCC and breast cancer risk
Dörk, Thilo ; Augustinsson, Annelie LU ; Olsson, Håkan LU
and Easton, Douglas F
(2019)
In Scientific Reports
9(1).
- Abstract
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of... (More)
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants. © 2019, The Author(s). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/44a2f43f-2c22-42dd-86e1-0f1dc32b451e
- author
- Dörk, Thilo
; Augustinsson, Annelie
LU
; Olsson, Håkan
LU
and Easton, Douglas F
- author collaboration
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 9
- issue
- 1
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85071631153
- pmid:31467304
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-019-48804-y
- language
- English
- LU publication?
- yes
- id
- 44a2f43f-2c22-42dd-86e1-0f1dc32b451e
- date added to LUP
- 2019-09-16 11:16:42
- date last changed
- 2022-03-25 23:05:09
@article{44a2f43f-2c22-42dd-86e1-0f1dc32b451e,
abstract = {{Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants. © 2019, The Author(s).}},
author = {{Dörk, Thilo and Augustinsson, Annelie and Olsson, Håkan and Easton, Douglas F}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Two truncating variants in FANCC and breast cancer risk}},
url = {{http://dx.doi.org/10.1038/s41598-019-48804-y}},
doi = {{10.1038/s41598-019-48804-y}},
volume = {{9}},
year = {{2019}},
}