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Two truncating variants in FANCC and breast cancer risk

Two truncating variants in FANCC and breast cancer risk
Two truncating variants in FANCC and breast cancer risk
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.
2045-2322
1-14
Dörk, Thilo
83d24239-fdde-4472-8644-6d9023c802f1
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
et al.
Dörk, Thilo
83d24239-fdde-4472-8644-6d9023c802f1
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c

Dörk, Thilo , et al. (2019) Two truncating variants in FANCC and breast cancer risk. Scientific Reports, 9, 1-14, [12524]. (doi:10.1038/s41598-019-48804-y).

Record type: Article

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.

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Submitted date: 2019
Accepted/In Press date: 9 August 2019
e-pub ahead of print date: 29 August 2019

Identifiers

Local EPrints ID: 433718
URI: http://eprints.soton.ac.uk/id/eprint/433718
ISSN: 2045-2322
PURE UUID: 69a4208a-7899-4abc-9e01-a83c4e26e8b2
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169
ORCID for William Tapper: ORCID iD orcid.org/0000-0002-5896-1889

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Date deposited: 02 Sep 2019 16:30
Last modified: 26 Nov 2021 02:42

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Contributors

Author: Thilo Dörk
Author: Diana Eccles ORCID iD
Author: William Tapper ORCID iD
Corporate Author: et al.

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