Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles

The Breast Cancer Susceptibility Collaboration (UK); Seal, Sheila; Thompson, Deborah; Renwick, Anthony; Elliott, Anna; Kelly, Patrick; Barfoot, Rita; Chagtai, Tasnim; Jayatilake, Hiran; Ahmed, Munaza; Spanova, Katarina; North, Bernard; McGuffog, Lesley; Evans, D Gareth; Eccles, Diana; Easton, Douglas F; Stratton, Michael R; Rahman, Nazneen

doi:10.1038/ng1902

Cited by 746BRCA gene mutations in cancerDNA Repair MechanismsGenetic factors in colorectal cancer

Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles

The Breast Cancer Susceptibility Collaboration (UK), Seal, Sheila, Thompson, Deborah, Renwick, Anthony, Elliott, Anna, Kelly, Patrick, Barfoot, Rita, Chagtai, Tasnim +10 more·2006·Nature Genetics

DOI 10.1038/ng1902

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Abstract

We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.

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The P47A variant, shown to disrupt FANCJ enzyme function, was found in controls of a later study and considered unrelated to breast cancer.
“For example, the P47A variant identified in 2001 [8] and shown to disrupt FANCJ enzyme function [56] was found in the controls of a subsequent study and considered to be unrelated to breast cancer [44].”
From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [44]
The most common FANCJ germline mutant allele is R798x.
“Of all the FANCJ germline mutations, the most common mutant allele is FANCJ R798x.”
From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [44]
At least four other distinct FANCJ-truncating mutations have been identified in breast cancer patients, but it is unclear whether these alleles express a truncated product.
“Similarly, at least four other distinct FANCJ-truncating mutations have been identified in breast cancer patients [44]; however, it is not clear whether these alleles express a truncated product.”
From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [44]

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ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ
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Authors: The Breast Cancer Susceptibility Collaboration (UK), Seal, S., Thompson, D., Renwick, A., Elliott, A., Kelly, P., Barfoot, R., Chagtai, T., Jayatilake, H., Ahmed, M., Spanova, K., North, B., McGuffog, L., Evans, D. G., Eccles, D., Easton, D. F., Stratton, M. R., & Rahman, N.
Affiliations: Institute of Cancer Research (GB)
University of Cambridge (GB)
St Mary's Hospital (GB)
Princess Anne Hospital (GB)
Corresponding author: Rahman, Nazneen
ORCID: Thompson, Deborah
North, Bernard
Evans, D Gareth
Eccles, Diana
Easton, Douglas F
Stratton, Michael R
Rahman, Nazneen
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2006-10-08
Volume: 38
Issue: 11
Pages: 1239-1241
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng1902
OpenAlex: W2126282065
Cited by: 746
References: 15
Citations by year: 2026: 10 · 2025: 20 · 2024: 16 · 2023: 47 · 2022: 20 · 2021: 26 · 2020: 36 · 2019: 24 · 2018: 24 · 2017: 31 · 2016: 47 · 2015: 45 · 2014: 53 · 2013: 47 · 2012: 48
FWCI: 29.99
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Funders: Wellcome Trust (068545/Z/02))
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: BRIP1, truncating mutations, breast cancer susceptibility, Fanconi anemia, FANCM, biallelic variants, hereditary breast cancer, relative risk
MeSH terms: Adult, Breast Neoplasms, DNA-Binding Proteins, Gene Frequency, Genetic Carrier Screening, Humans, Middle Aged, Pedigree, Codon, Nonsense, Penetrance, Genetic Predisposition to Disease, RNA Helicases, Fanconi Anemia Complementation Group Proteins

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Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles

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