Genome-wide association study identifies new prostate cancer susceptibility loci

F.R. Schumacher; S.I. Berndt; A. Siddiq; K.B. Jacobs; Z. Wang; S. Lindstrom; V.L. Stevens; C. Chen; A.M. Mondul; R.C. Travis; D. Stram; R.A. Eeles; D.F. Easton; G. Giles; J.L. Hopper; D.E. Neal; F.C. Hamdy; J.L. Donovan; K. Muir; A.A.A. Olama; Z. Kote-Jarai; M. Guy; G. Severi; H. Grönberg; W.B. Isaacs; R. Karlsson; F. Wiklund; J. Xu; N.E. Allen; G.L. Andriole; A. Barricarte; H. Boing; H.B. Bueno-de-Mesquite; E.D. Crawford; W.R. Diver; J.M. Gonzalez; E.L. Giovannucci; M. Johansson; L.L. Marchand; J. Ma; S. Sieri; P. Stattin; M.J. Stampfer; A. Tjonneland; P. Vineis; J. Virtamo; Ulla Birgitte Vogel; S.J. Weinstein; M. Yeager; M.J. Thun; L.N. Kolonel; B.E. Henderson; D. Albanes; R.B. Hayes; H.S. Feigelson; E. Riboli; D.J. Hunter; S.J. Chanock; C.A. Haiman

doi:10.1093/hmg/ddr295

Genome-wide association study identifies new prostate cancer susceptibility loci

F.R. Schumacher
, S.I. Berndt
, A. Siddiq
, K.B. Jacobs
, Z. Wang
, S. Lindstrom
, V.L. Stevens
, C. Chen
, A.M. Mondul
, R.C. Travis
, D. Stram
, R.A. Eeles
, D.F. Easton
, G. Giles
, J.L. Hopper
, D.E. Neal
, F.C. Hamdy
, J.L. Donovan
, K. Muir
, A.A.A. Olama

Z. Kote-Jarai, M. Guy, G. Severi, H. Grönberg, W.B. Isaacs, R. Karlsson, F. Wiklund, J. Xu, N.E. Allen, G.L. Andriole, A. Barricarte, H. Boing, H.B. Bueno-de-Mesquite, E.D. Crawford, W.R. Diver, J.M. Gonzalez, E.L. Giovannucci, M. Johansson, L.L. Marchand, J. Ma, S. Sieri, P. Stattin, M.J. Stampfer, A. Tjonneland, P. Vineis, J. Virtamo, Ulla Birgitte Vogel, S.J. Weinstein, M. Yeager, M.J. Thun, L.N. Kolonel, B.E. Henderson, D. Albanes, R.B. Hayes, H.S. Feigelson, E. Riboli, D.J. Hunter, S.J. Chanock, C.A. Haiman

Department of Chemistry and Microbiology

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade = 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P <0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10-8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10-9). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.

Original language	English
Journal	Human Molecular Genetics
Volume	20
Issue number	19
Pages (from-to)	3867-3875
Number of pages	9
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddr295
Publication status	Published - 2011

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10.1093/hmg/ddr295

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Schumacher, F. R., Berndt, S. I., Siddiq, A., Jacobs, K. B., Wang, Z., Lindstrom, S., Stevens, V. L., Chen, C., Mondul, A. M., Travis, R. C., Stram, D., Eeles, R. A., Easton, D. F., Giles, G., Hopper, J. L., Neal, D. E., Hamdy, F. C., Donovan, J. L., Muir, K., ... Haiman, C. A. (2011). Genome-wide association study identifies new prostate cancer susceptibility loci. Human Molecular Genetics, 20(19), 3867-3875. https://doi.org/10.1093/hmg/ddr295

@article{46f8506289134e6cac5b85ef3f0d9275,

title = "Genome-wide association study identifies new prostate cancer susceptibility loci",

abstract = "Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade = 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P <0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10-8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10-9). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.",

author = "F.R. Schumacher and S.I. Berndt and A. Siddiq and K.B. Jacobs and Z. Wang and S. Lindstrom and V.L. Stevens and C. Chen and A.M. Mondul and R.C. Travis and D. Stram and R.A. Eeles and D.F. Easton and G. Giles and J.L. Hopper and D.E. Neal and F.C. Hamdy and J.L. Donovan and K. Muir and A.A.A. Olama and Z. Kote-Jarai and M. Guy and G. Severi and H. Gr{\"o}nberg and W.B. Isaacs and R. Karlsson and F. Wiklund and J. Xu and N.E. Allen and G.L. Andriole and A. Barricarte and H. Boing and H.B. Bueno-de-Mesquite and E.D. Crawford and W.R. Diver and J.M. Gonzalez and E.L. Giovannucci and M. Johansson and L.L. Marchand and J. Ma and S. Sieri and P. Stattin and M.J. Stampfer and A. Tjonneland and P. Vineis and J. Virtamo and Vogel, \{Ulla Birgitte\} and S.J. Weinstein and M. Yeager and M.J. Thun and L.N. Kolonel and B.E. Henderson and D. Albanes and R.B. Hayes and H.S. Feigelson and E. Riboli and D.J. Hunter and S.J. Chanock and C.A. Haiman",

note = "SUBMISSIONYEAR:2011",

year = "2011",

doi = "10.1093/hmg/ddr295",

language = "English",

volume = "20",

pages = "3867--3875",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "19",

}

Schumacher, FR, Berndt, SI, Siddiq, A, Jacobs, KB, Wang, Z, Lindstrom, S, Stevens, VL, Chen, C, Mondul, AM, Travis, RC, Stram, D, Eeles, RA, Easton, DF, Giles, G, Hopper, JL, Neal, DE, Hamdy, FC, Donovan, JL, Muir, K, Olama, AAA, Kote-Jarai, Z, Guy, M, Severi, G, Grönberg, H, Isaacs, WB, Karlsson, R, Wiklund, F, Xu, J, Allen, NE, Andriole, GL, Barricarte, A, Boing, H, Bueno-de-Mesquite, HB, Crawford, ED, Diver, WR, Gonzalez, JM, Giovannucci, EL, Johansson, M, Marchand, LL, Ma, J, Sieri, S, Stattin, P, Stampfer, MJ, Tjonneland, A, Vineis, P, Virtamo, J, Vogel, UB, Weinstein, SJ, Yeager, M, Thun, MJ, Kolonel, LN, Henderson, BE, Albanes, D, Hayes, RB, Feigelson, HS, Riboli, E, Hunter, DJ, Chanock, SJ & Haiman, CA 2011, 'Genome-wide association study identifies new prostate cancer susceptibility loci', Human Molecular Genetics, vol. 20, no. 19, pp. 3867-3875. https://doi.org/10.1093/hmg/ddr295

TY - JOUR

T1 - Genome-wide association study identifies new prostate cancer susceptibility loci

AU - Schumacher, F.R.

AU - Berndt, S.I.

AU - Siddiq, A.

AU - Jacobs, K.B.

AU - Wang, Z.

AU - Lindstrom, S.

AU - Stevens, V.L.

AU - Chen, C.

AU - Mondul, A.M.

AU - Travis, R.C.

AU - Stram, D.

AU - Eeles, R.A.

AU - Easton, D.F.

AU - Giles, G.

AU - Hopper, J.L.

AU - Neal, D.E.

AU - Hamdy, F.C.

AU - Donovan, J.L.

AU - Muir, K.

AU - Olama, A.A.A.

AU - Kote-Jarai, Z.

AU - Guy, M.

AU - Severi, G.

AU - Grönberg, H.

AU - Isaacs, W.B.

AU - Karlsson, R.

AU - Wiklund, F.

AU - Xu, J.

AU - Allen, N.E.

AU - Andriole, G.L.

AU - Barricarte, A.

AU - Boing, H.

AU - Bueno-de-Mesquite, H.B.

AU - Crawford, E.D.

AU - Diver, W.R.

AU - Gonzalez, J.M.

AU - Giovannucci, E.L.

AU - Johansson, M.

AU - Marchand, L.L.

AU - Ma, J.

AU - Sieri, S.

AU - Stattin, P.

AU - Stampfer, M.J.

AU - Tjonneland, A.

AU - Vineis, P.

AU - Virtamo, J.

AU - Vogel, Ulla Birgitte

AU - Weinstein, S.J.

AU - Yeager, M.

AU - Thun, M.J.

AU - Kolonel, L.N.

AU - Henderson, B.E.

AU - Albanes, D.

AU - Hayes, R.B.

AU - Feigelson, H.S.

AU - Riboli, E.

AU - Hunter, D.J.

AU - Chanock, S.J.

AU - Haiman, C.A.

N1 - SUBMISSIONYEAR:2011

PY - 2011

Y1 - 2011

N2 - Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade = 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P <0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10-8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10-9). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.

AB - Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade = 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P <0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10-8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10-9). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.

U2 - 10.1093/hmg/ddr295

DO - 10.1093/hmg/ddr295

M3 - Journal article

SN - 0964-6906

VL - 20

SP - 3867

EP - 3875

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -

Genome-wide association study identifies new prostate cancer susceptibility loci

Abstract

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