Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08

AUTHORS

Craig C. Teerlink, Daniel Leongamornlert, Tokhir Dadaev, Alun Thomas, James Farnham, Robert A. Stephenson, Shaun Riska, Shannon K. McDonnell, Daniel J. Schaid, William J. Catalona, S. Lilly Zheng, Kathleen A. Cooney, Anna M. Ray, Kimberly A. Zuhlke, Ethan M. Lange, Graham G. Giles, Melissa C. Southey, Liesel M. Fitzgerald, Antje Rinckleb, Manuel Luedeke, Christiane Maier, Janet L. Stanford, Elaine A. Ostrander, Elina M. Kaikkonen, Csilla Sipeky, Teuvo Tammela, Johanna Schleutker, Kathleen E. Wiley, Sarah D. Isaacs, Patrick C. Walsh, William B. Isaacs, Jianfeng Xu, Geraldine Cancel-Tassin, Olivier Cussenot, Diptasri Mandal, Cecelia Laurie, Cathy Laurie, The PRACTICAL consortium, International Consortium for Prostate Cancer Genetics, Stephen N. Thibodeau, Rosalind A. Eeles, Zsofia Kote-Jarai, Lisa Cannon-Albright

ABSTRACT

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e(-8)) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e(-11)). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus. More... »

PAGES

923-938

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00439-016-1690-6

    DOI

    http://dx.doi.org/10.1007/s00439-016-1690-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1011561241

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27262462


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