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

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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)347-356
Number of pages10
JournalHuman Genetics
Volume133
Issue number3
DOIs
StatePublished - Mar 2014

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Single Nucleotide Polymorphism
Prostatic Neoplasms
Genome-Wide Association Study
Pedigree
Software
Alleles
Familial Prostate cancer
Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

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

In: Human Genetics, Vol. 133, No. 3, 03.2014, p. 347-356.

Research output: Contribution to journalArticle

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, CL, Catalona, WJ, Zheng, SL, Jin, G, Lu, L, Xu, J, Camp, NJ & Cannon-Albright, LA 2014, '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', Human Genetics, vol. 133, no. 3, pp. 347-356. https://doi.org/10.1007/s00439-013-1384-2
Teerlink, Craig C. ; Thibodeau, Stephen N ; McDonnell, Shannon K. ; Schaid, Daniel J ; Rinckleb, Antje ; Maier, Christiane ; Vogel, Walther ; Cancel-Tassin, Geraldine ; Egrot, Christophe ; Cussenot, Olivier ; Foulkes, William D. ; Giles, Graham G. ; Hopper, John L. ; Severi, Gianluca ; Eeles, Ros ; Easton, Douglas ; Kote-Jarai, Zsofia ; Guy, Michelle ; Cooney, Kathleen A. ; Ray, Anna M. ; Zuhlke, Kimberly A. ; Lange, Ethan M. ; Fitzgerald, Liesel M. ; Stanford, Janet L. ; Ostrander, Elaine A. ; Wiley, Kathleen E. ; Isaacs, Sarah D. ; Walsh, Patrick C. ; Isaacs, William B. ; Wahlfors, Tiina ; Tammela, Teuvo ; Schleutker, Johanna ; Wiklund, Fredrik ; Grönberg, Henrik ; Emanuelsson, Monica ; Carpten, John ; Bailey-Wilson, Joan ; Whittemore, Alice S. ; Oakley-Girvan, Ingrid ; Hsieh, Chih Lin ; Catalona, William J. ; Zheng, S. Lilly ; Jin, Guangfu ; Lu, Lingyi ; Xu, Jianfeng ; Camp, Nicola J. ; Cannon-Albright, Lisa A. / 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. In: Human Genetics. 2014 ; Vol. 133, No. 3. pp. 347-356.
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title = "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",
abstract = "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.",
author = "Teerlink, {Craig C.} and Thibodeau, {Stephen N} and McDonnell, {Shannon K.} and Schaid, {Daniel J} and Antje Rinckleb and Christiane Maier and Walther Vogel and Geraldine Cancel-Tassin and Christophe Egrot and Olivier Cussenot and Foulkes, {William D.} and Giles, {Graham G.} and Hopper, {John L.} and Gianluca Severi and Ros Eeles and Douglas Easton and Zsofia Kote-Jarai and Michelle Guy and Cooney, {Kathleen A.} and Ray, {Anna M.} and Zuhlke, {Kimberly A.} and Lange, {Ethan M.} and Fitzgerald, {Liesel M.} and Stanford, {Janet L.} and Ostrander, {Elaine A.} and Wiley, {Kathleen E.} and Isaacs, {Sarah D.} and Walsh, {Patrick C.} and Isaacs, {William B.} and Tiina Wahlfors and Teuvo Tammela and Johanna Schleutker and Fredrik Wiklund and Henrik Gr{\"o}nberg and Monica Emanuelsson and John Carpten and Joan Bailey-Wilson and Whittemore, {Alice S.} and Ingrid Oakley-Girvan and Hsieh, {Chih Lin} and Catalona, {William J.} and Zheng, {S. Lilly} and Guangfu Jin and Lingyi Lu and Jianfeng Xu and Camp, {Nicola J.} and Cannon-Albright, {Lisa A.}",
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T1 - 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

AU - Teerlink, Craig C.

AU - Thibodeau, Stephen N

AU - McDonnell, Shannon K.

AU - Schaid, Daniel J

AU - Rinckleb, Antje

AU - Maier, Christiane

AU - Vogel, Walther

AU - Cancel-Tassin, Geraldine

AU - Egrot, Christophe

AU - Cussenot, Olivier

AU - Foulkes, William D.

AU - Giles, Graham G.

AU - Hopper, John L.

AU - Severi, Gianluca

AU - Eeles, Ros

AU - Easton, Douglas

AU - Kote-Jarai, Zsofia

AU - Guy, Michelle

AU - Cooney, Kathleen A.

AU - Ray, Anna M.

AU - Zuhlke, Kimberly A.

AU - Lange, Ethan M.

AU - Fitzgerald, Liesel M.

AU - Stanford, Janet L.

AU - Ostrander, Elaine A.

AU - Wiley, Kathleen E.

AU - Isaacs, Sarah D.

AU - Walsh, Patrick C.

AU - Isaacs, William B.

AU - Wahlfors, Tiina

AU - Tammela, Teuvo

AU - Schleutker, Johanna

AU - Wiklund, Fredrik

AU - Grönberg, Henrik

AU - Emanuelsson, Monica

AU - Carpten, John

AU - Bailey-Wilson, Joan

AU - Whittemore, Alice S.

AU - Oakley-Girvan, Ingrid

AU - Hsieh, Chih Lin

AU - Catalona, William J.

AU - Zheng, S. Lilly

AU - Jin, Guangfu

AU - Lu, Lingyi

AU - Xu, Jianfeng

AU - Camp, Nicola J.

AU - Cannon-Albright, Lisa A.

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

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