Multiple loci identified in a genome-wide association study of prostate cancer

Gilles Thomas; Kevin B Jacobs; Meredith Yeager; Peter Kraft; Sholom Wacholder; Nick Orr; Kai Yu; Nilanjan Chatterjee; Robert W Welch; Amy Hutchinson; Andrew Crenshaw; Geraldine Cancel-Tassin; Brian J Staats; Zhaoming Wang; Jesus Gonzalez-Bosquet; Jun Fang; Xiang Deng; Sonja I Berndt; Eugenia E Calle; Heather Spencer Feigelson; Michael J Thun; Carmen Rodriguez; Demetrius Albanes; Jarmo Virtamo; Stephanie Weinstein; Fredrick R. Schumacher; Edward Giovannucci; Walter C Willett; Olivier Cussenot; Antoine Valeri; Gerald L Andriole; E David Crawford; Margaret Tucker; Daniela S Gerhard; Joseph F Fraumeni; Robert Hoover; Richard B Hayes; David J Hunter; Stephen J.  Chanock

doi:10.1038/ng.91

Multiple loci identified in a genome-wide association study of prostate cancer

Gilles Thomas, Kevin B Jacobs, Meredith Yeager, Peter Kraft, Sholom Wacholder, Nick Orr, Kai Yu, Nilanjan Chatterjee, Robert W Welch, Amy Hutchinson, Andrew Crenshaw, Geraldine Cancel-Tassin, Brian J Staats, Zhaoming Wang, Jesus Gonzalez-Bosquet, Jun Fang, Xiang Deng, Sonja I Berndt, Eugenia E Calle, Heather Spencer FeigelsonMichael J Thun, Carmen Rodriguez, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Fredrick R. Schumacher, Edward Giovannucci, Walter C Willett, Olivier Cussenot, Antoine Valeri, Gerald L Andriole, E David Crawford, Margaret Tucker, Daniela S Gerhard, Joseph F Fraumeni, Robert Hoover, Richard B Hayes, David J Hunter, Stephen J. Chanock

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

808 Citations (Scopus)

Abstract

We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.

Original language	English
Pages (from-to)	310-5
Number of pages	6
Journal	Nature Genetics
Volume	40
Issue number	3
DOIs	https://doi.org/10.1038/ng.91
Publication status	Published - Mar 2008

Keywords

Cadherins
Case-Control Studies
Chromosome Mapping
DNA Mutational Analysis
European Continental Ancestry Group
Gene Frequency
Genetic Linkage
Genetic Predisposition to Disease
Genome, Human
Humans
Interleukin-16
Linkage Disequilibrium
Male
Phosphoproteins
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Quantitative Trait Loci
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.91

Cite this

Thomas, G., Jacobs, K. B., Yeager, M., Kraft, P., Wacholder, S., Orr, N., Yu, K., Chatterjee, N., Welch, R. W., Hutchinson, A., Crenshaw, A., Cancel-Tassin, G., Staats, B. J., Wang, Z., Gonzalez-Bosquet, J., Fang, J., Deng, X., Berndt, S. I., Calle, E. E., ... Chanock, S. J. (2008). Multiple loci identified in a genome-wide association study of prostate cancer. Nature Genetics, 40(3), 310-5. https://doi.org/10.1038/ng.91

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title = "Multiple loci identified in a genome-wide association study of prostate cancer",

abstract = "We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.",

keywords = "Cadherins, Case-Control Studies, Chromosome Mapping, DNA Mutational Analysis, European Continental Ancestry Group, Gene Frequency, Genetic Linkage, Genetic Predisposition to Disease, Genome, Human, Humans, Interleukin-16, Linkage Disequilibrium, Male, Phosphoproteins, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Quantitative Trait Loci, Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't",

author = "Gilles Thomas and Jacobs, {Kevin B} and Meredith Yeager and Peter Kraft and Sholom Wacholder and Nick Orr and Kai Yu and Nilanjan Chatterjee and Welch, {Robert W} and Amy Hutchinson and Andrew Crenshaw and Geraldine Cancel-Tassin and Staats, {Brian J} and Zhaoming Wang and Jesus Gonzalez-Bosquet and Jun Fang and Xiang Deng and Berndt, {Sonja I} and Calle, {Eugenia E} and Feigelson, {Heather Spencer} and Thun, {Michael J} and Carmen Rodriguez and Demetrius Albanes and Jarmo Virtamo and Stephanie Weinstein and Schumacher, {Fredrick R.} and Edward Giovannucci and Willett, {Walter C} and Olivier Cussenot and Antoine Valeri and Andriole, {Gerald L} and Crawford, {E David} and Margaret Tucker and Gerhard, {Daniela S} and Fraumeni, {Joseph F} and Robert Hoover and Hayes, {Richard B} and Hunter, {David J} and Chanock, {Stephen J.}",

year = "2008",

month = mar,

doi = "10.1038/ng.91",

language = "English",

volume = "40",

pages = "310--5",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

}

Thomas, G, Jacobs, KB, Yeager, M, Kraft, P, Wacholder, S, Orr, N, Yu, K, Chatterjee, N, Welch, RW, Hutchinson, A, Crenshaw, A, Cancel-Tassin, G, Staats, BJ, Wang, Z, Gonzalez-Bosquet, J, Fang, J, Deng, X, Berndt, SI, Calle, EE, Feigelson, HS, Thun, MJ, Rodriguez, C, Albanes, D, Virtamo, J, Weinstein, S, Schumacher, FR, Giovannucci, E, Willett, WC, Cussenot, O, Valeri, A, Andriole, GL, Crawford, ED, Tucker, M, Gerhard, DS, Fraumeni, JF, Hoover, R, Hayes, RB, Hunter, DJ & Chanock, SJ 2008, 'Multiple loci identified in a genome-wide association study of prostate cancer', Nature Genetics, vol. 40, no. 3, pp. 310-5. https://doi.org/10.1038/ng.91

TY - JOUR

T1 - Multiple loci identified in a genome-wide association study of prostate cancer

AU - Thomas, Gilles

AU - Jacobs, Kevin B

AU - Yeager, Meredith

AU - Kraft, Peter

AU - Wacholder, Sholom

AU - Orr, Nick

AU - Yu, Kai

AU - Chatterjee, Nilanjan

AU - Welch, Robert W

AU - Hutchinson, Amy

AU - Crenshaw, Andrew

AU - Cancel-Tassin, Geraldine

AU - Staats, Brian J

AU - Wang, Zhaoming

AU - Gonzalez-Bosquet, Jesus

AU - Fang, Jun

AU - Deng, Xiang

AU - Berndt, Sonja I

AU - Calle, Eugenia E

AU - Feigelson, Heather Spencer

AU - Thun, Michael J

AU - Rodriguez, Carmen

AU - Albanes, Demetrius

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie

AU - Schumacher, Fredrick R.

AU - Giovannucci, Edward

AU - Willett, Walter C

AU - Cussenot, Olivier

AU - Valeri, Antoine

AU - Andriole, Gerald L

AU - Crawford, E David

AU - Tucker, Margaret

AU - Gerhard, Daniela S

AU - Fraumeni, Joseph F

AU - Hoover, Robert

AU - Hayes, Richard B

AU - Hunter, David J

AU - Chanock, Stephen J.

PY - 2008/3

Y1 - 2008/3

N2 - We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.

AB - We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.

KW - Cadherins

KW - Case-Control Studies

KW - Chromosome Mapping

KW - DNA Mutational Analysis

KW - European Continental Ancestry Group

KW - Gene Frequency

KW - Genetic Linkage

KW - Genetic Predisposition to Disease

KW - Genome, Human

KW - Humans

KW - Interleukin-16

KW - Linkage Disequilibrium

KW - Male

KW - Phosphoproteins

KW - Polymorphism, Single Nucleotide

KW - Prostatic Neoplasms

KW - Quantitative Trait Loci

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, N.I.H., Intramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ng.91

DO - 10.1038/ng.91

M3 - Article

C2 - 18264096

SN - 1061-4036

VL - 40

SP - 310

EP - 315

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Multiple loci identified in a genome-wide association study of prostate cancer

Abstract

Keywords

UN SDGs

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