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

Publication ,  Journal Article
Teerlink, CC; Leongamornlert, D; Dadaev, T; Thomas, A; Farnham, J; Stephenson, RA; Riska, S; McDonnell, SK; Schaid, DJ; Catalona, WJ; Zheng, SL ...
Published in: Hum Genet
August 2016

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.

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Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

August 2016

Volume

135

Issue

8

Start / End Page

923 / 938

Location

Germany

Related Subject Headings

  • Tumor Suppressor Proteins
  • Risk Factors
  • RNA, Long Noncoding
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Pedigree
  • Middle Aged
  • Male
  • Humans
  • Heterozygote
 

Citation

APA
Chicago
ICMJE
MLA
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Teerlink, C. C., Leongamornlert, D., Dadaev, T., Thomas, A., Farnham, J., Stephenson, R. A., … Cannon-Albright, L. (2016). Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21. Hum Genet, 135(8), 923–938. https://doi.org/10.1007/s00439-016-1690-6
Teerlink, Craig C., Daniel Leongamornlert, Tokhir Dadaev, Alun Thomas, James Farnham, Robert A. Stephenson, Shaun Riska, et al. “Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21.Hum Genet 135, no. 8 (August 2016): 923–38. https://doi.org/10.1007/s00439-016-1690-6.
Teerlink CC, Leongamornlert D, Dadaev T, Thomas A, Farnham J, Stephenson RA, et al. Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21. Hum Genet. 2016 Aug;135(8):923–38.
Teerlink, Craig C., et al. “Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21.Hum Genet, vol. 135, no. 8, Aug. 2016, pp. 923–38. Pubmed, doi:10.1007/s00439-016-1690-6.
Teerlink CC, Leongamornlert D, Dadaev T, Thomas A, Farnham J, Stephenson RA, Riska S, McDonnell SK, Schaid DJ, Catalona WJ, Zheng SL, Cooney KA, Ray AM, Zuhlke KA, Lange EM, Giles GG, Southey MC, Fitzgerald LM, Rinckleb A, Luedeke M, Maier C, Stanford JL, Ostrander EA, Kaikkonen EM, Sipeky C, Tammela T, Schleutker J, Wiley KE, Isaacs SD, Walsh PC, Isaacs WB, Xu J, Cancel-Tassin G, Cussenot O, Mandal D, Laurie C, PRACTICAL consortium, International Consortium for Prostate Cancer Genetics, Thibodeau SN, Eeles RA, Kote-Jarai Z, Cannon-Albright L. Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21. Hum Genet. 2016 Aug;135(8):923–938.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

August 2016

Volume

135

Issue

8

Start / End Page

923 / 938

Location

Germany

Related Subject Headings

  • Tumor Suppressor Proteins
  • Risk Factors
  • RNA, Long Noncoding
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Pedigree
  • Middle Aged
  • Male
  • Humans
  • Heterozygote