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A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability

Lookup NU author(s): Professor Dawn Teare, Professor Louise Parker, Professor Sir John Burn

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Abstract

Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair1,2. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence3,4. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% Cl, 1.07-1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.


Publication metadata

Author(s): Healey CS, Dunning AM, Teare MD, Chase D, Parker L, Burn J, Chang-Claude J, Mannermaa A, Kataja V, Huntsman DG, Pharoah PDP, Luben RN, Easton DF, Ponder BAJ

Publication type: Letter

Publication status: Published

Journal: Nature Genetics

Year: 2000

Volume: 26

Issue: 3

Pages: 362-364

Print publication date: 01/01/2000

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

URL: http://dx.doi.org/10.1038/81691

DOI: 10.1038/81691

PubMed id: 11062481


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