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Published in: BMC Cancer 1/2005

Open Access 01-12-2005 | Research article

Common variation in EMSYand risk of breast and ovarian cancer: a case-control study using HapMap tagging SNPs

Authors: Patrick R Benusiglio, Fabienne Lesueur, Craig Luccarini, Joan McIntosh, Robert N Luben, Paula Smith, Alison Dunning, Douglas F Easton, Bruce AJ Ponder, Paul D Pharoah

Published in: BMC Cancer | Issue 1/2005

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Abstract

Background

EMSY could be involved in low-level susceptibility to breast and ovarian cancer. Gene amplification is seen in a proportion of breast and ovarian tumours and correlates with poor prognosis in breast cancer patients. Furthermore, the EMSY protein silences a transcription activation domain in BRCA2 exon 3.

Methods

We used a genetic association study design to determine if common genetic variation (frequency ≥ 5%) in EMSY was associated with breast or ovarian cancer risk in the British population. Haplotype tagging single-nucleotide polymorphisms (htSNPs) were selected from the HapMap database and genotyped using Taqman® in two large study sets of white British women (n [breast set] = 2343 cases and 2284 controls, n [ovarian set] = 864 cases and 864 controls). HapMap data might be insufficient to tag genetic variation in EMSY comprehensively. We therefore screened the gene promoter and coding sequences with denaturing high performance liquid chromatography in order to identify additional SNPs that are most likely to be functional.

Results

HapMap data on 22 SNPs show that 4 htSNPs tag 4 common haplotypes: rs2282611 (5'up t>g), rs4245443 (IVS7 g>a), rs2513511 (IVS16 a>g), rs2155220 (3'down c>t). We observed no association between any of the genotypes or associated haplotypes and breast or ovarian cancer risk. Seventeen out of the 18 remaining HapMap polymorphisms (94%) were well tagged by the 4 selected htSNPs (r2 s > 0.8). Genotype frequencies for two further SNPs identified by screening and located near exon-intron boundaries, rs2508740 (IVS9 a>g) and rs11600501 (IVS10 c>t), were also similar in cases and controls. In order to simulate unidentified SNPs, we performed the leave-one-out cross-validation procedure on the HapMap data; over 95% of the common genetic variation was well represented by tagging polymorphisms. We are therefore likely to have tagged any common, functional variants present in our population.

Conclusion

We found no association between common genetic variation in EMSY and risk of breast or ovarian cancer in two large study sets of white British women.
Appendix
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Metadata
Title
Common variation in EMSYand risk of breast and ovarian cancer: a case-control study using HapMap tagging SNPs
Authors
Patrick R Benusiglio
Fabienne Lesueur
Craig Luccarini
Joan McIntosh
Robert N Luben
Paula Smith
Alison Dunning
Douglas F Easton
Bruce AJ Ponder
Paul D Pharoah
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2005
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-5-81

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