In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 5065-5065
Abstract:
The HOXB13 gene has been implicated in prostate cancer susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 prostate cancer cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with prostate cancer risk, described by rs117576373, OR 1.30, P = 2.62×10-14. Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene, G84E, rs138213197, which has been identified recently as a moderate penetrance prostate cancer susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility. Citation Format: Zsofia Kote-Jarai, Edward Saunders, Tokhir Dadaev, Daniel Leongamornlert, Sarah Jugurnauth-Little, Malgorzata Tymrakiewicz, Koveela Govindasami, Fredrik Wiklund, Ali Amin Al Olama, Sara Benlloch, The PRACTICAL Consortium, Douglas Easton, Keneth Muir, Rosalind Eeles. Fine-mapping the HOXB region detects common variants tagging a rare coding allele: Evidence for synthetic association in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5065. doi:10.1158/1538-7445.AM2014-5065
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-5065
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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