Two truncating variants in FANCC and breast cancer risk
Date
2019
Authors
Dork, Thilo
Peterlongo, Paolo
Mannermaa, Arto
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Ahearn, Thomas
Andrulis, Irene L
Anton-Culver, Hoda
Arndt, Volker
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Nature Publishing Group
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 diferences 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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Scientific Reports
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Journal article
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