Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: Evidence from the International Consortium for Prostate Cancer Genetics (ICPCG)

Guangfu Jin, Lingyi Lu, Kathleen A. Cooney, Anna M. Ray, Kimberly A. Zuhlke, Ethan M. Lange, Lisa A. Cannon-Albright, Nicola J. Camp, Craig C. Teerlink, Liesel M. Fitzgerald, Janet L. Stanford, Kathleen E. Wiley, Sarah D. Isaacs, Patrick C. Walsh, William D. Foulkes, Graham G. Giles, John L. Hopper, Gianluca Severi, Ros Eeles, Doug EastonZsofia Kote-Jarai, Michelle Guy, Antje Rinckleb, Christiane Maier, Walther Vogel, Geraldine Cancel-Tassin, Christophe Egrot, Olivier Cussenot, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Fredrik Wiklund, Henrik Grönberg, Monica Emanuelsson, Alice S. Whittemore, Ingrid Oakley-Girvan, Chih Lin Hsieh, Tiina Wahlfors, Teuvo Tammela, Johanna Schleutker, William J. Catalona, S. Lilly Zheng, Elaine A. Ostrander, William B. Isaacs, Jianfeng Xu

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.

Original languageEnglish (US)
Pages (from-to)1095-1103
Number of pages9
JournalHuman genetics
Volume131
Issue number7
DOIs
StatePublished - Jul 2012

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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