Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease.

Published

Journal Article

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.

Full Text

Duke Authors

Cited Authors

  • Teerlink, CC; Thibodeau, SN; McDonnell, SK; Schaid, DJ; Rinckleb, A; Maier, C; Vogel, W; Cancel-Tassin, G; Egrot, C; Cussenot, O; Foulkes, WD; Giles, GG; Hopper, JL; Severi, G; Eeles, R; Easton, D; Kote-Jarai, Z; Guy, M; Cooney, KA; Ray, AM; Zuhlke, KA; Lange, EM; Fitzgerald, LM; Stanford, JL; Ostrander, EA; Wiley, KE; Isaacs, SD; Walsh, PC; Isaacs, WB; Wahlfors, T; Tammela, T; Schleutker, J; Wiklund, F; Grönberg, H; Emanuelsson, M; Carpten, J; Bailey-Wilson, J; Whittemore, AS; Oakley-Girvan, I; Hsieh, C-L; Catalona, WJ; Zheng, SL; Jin, G; Lu, L; Xu, J; International Consortium for Prostate Cancer Genetics, ; Camp, NJ; Cannon-Albright, LA

Published Date

  • March 2014

Published In

Volume / Issue

  • 133 / 3

Start / End Page

  • 347 - 356

PubMed ID

  • 24162621

Pubmed Central ID

  • 24162621

Electronic International Standard Serial Number (EISSN)

  • 1432-1203

Digital Object Identifier (DOI)

  • 10.1007/s00439-013-1384-2

Language

  • eng

Conference Location

  • Germany