In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Breast cancer susceptibility variants alter risks in familial disease.

Latif, Ayse; Hadfield, Kristen D; Roberts, Stephen A; Shenton, Andrew; Lalloo, Fiona; Black, Graeme C M; Howell, Anthony; Evans, D Gareth; Newman, William G

Journal of medical genetics. 2010;47(2):126-31.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:

Full-text held externally

Abstract

BACKGROUND: Recent candidate and genome-wide association studies have identified variants altering susceptibility to breast cancer. OBJECTIVE: To establish the relevance of these variants to breast cancer risk in familial breast cancer cases both with and without BRCA1 or BRCA2 (BRCA1/2) mutations. METHODS:A cohort of unrelated individuals with breast cancer due to the presence of either BRCA1 (121) or BRCA2 mutations (109) and individuals with familial breast cancer not due to BRCA1/2 mutations (722) were genotyped using Taqman SNP Genotyping Assays. Allele frequencies were compared with an ethnically and gender-matched group (436). RESULTS: A synonymous variant (Ser51) in TOX3 (previously TNRC9) was associated with an increased risk of breast cancer (OR=1.82, p<0.001) in BRCA2 mutation carriers. The associations for FGFR2 (OR=1.20, p=0.046), TOX3 (OR=1.5, p<0.001), MAP3K1 (OR=1.26 p=0.03), CASP8 (OR=0.73 p=0.02) and the chromosome 8-associated SNP (OR=1.31, p=0.004) were replicated in individuals without BRCA1/2 mutations. In addition, homozygote carriers of MAP3K1 variants were shown to have a significantly lower Manchester Score (mean 13.8-17.6, p=0.003), whereas individuals carrying one or two copies of the FGFR2 variant had a higher Manchester Score (mean 17.5-17.9, p=0.01). CONCLUSIONS:This study confirms that susceptibility variants in FGFR2, TOX3 and MAP3K1 and on chromosome 8q are all associated with increased risk of cancer in individuals with a family history of breast cancer, whereas CASP8 is protective in this context. The level of risk is dependent on the strength of the family history and the presence of a BRCA1/2 mutation and contributes to the understanding of the use of these variants in clinical risk prediction.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Published date:
Language:
eng
Abbreviated journal title:
ISSN:
Place of publication:
England
Volume:
47
Issue:
2
Pagination:
126-31
Digital Object Identifier:
10.1136/jmg.2009.067256
Pubmed Identifier:
19617217
Pii Identifier:
jmg.2009.067256
Attached files embargo period:
Immediate release
Attached files release date:
21st April, 2015
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:101723
Created by:
Newman, William
Created:
22nd December, 2010, 16:43:04
Last modified by:
Newman, William
Last modified:
21st April, 2015, 17:43:05

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.