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 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

Research output: Contribution to journalArticle

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 × 10-13 and P <2.14 × 10-6). Loci on chromosome 10 include MSMB, which encodes Β-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 × 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 languageEnglish (US)
Pages (from-to)310-315
Number of pages6
JournalNature Genetics
Volume40
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Prostatic Neoplasms
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 7
Interleukin-16
Endometrial Neoplasms
Tumor Biomarkers
Semen
Early Detection of Cancer
Ovarian Neoplasms
Genes
Colorectal Neoplasms
Lung Neoplasms
Chromosomes
Prospective Studies

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Thomas, G., Jacobs, K. B., Yeager, M., Kraft, P., Wacholder, S., Orr, N., ... Chanock, S. J. (2008). Multiple loci identified in a genome-wide association study of prostate cancer. Nature Genetics, 40(3), 310-315. https://doi.org/10.1038/ng.91

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

In: Nature Genetics, Vol. 40, No. 3, 03.2008, p. 310-315.

Research output: Contribution to journalArticle

Thomas, G, Jacobs, KB, Yeager, M, Kraft, P, Wacholder, S, Orr, N, Yu, K, Chatterjee, N, Welch, R, 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. 310-315. https://doi.org/10.1038/ng.91
Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholder S, Orr N et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nature Genetics. 2008 Mar;40(3):310-315. https://doi.org/10.1038/ng.91
Thomas, Gilles ; Jacobs, Kevin B. ; Yeager, Meredith ; Kraft, Peter ; Wacholder, Sholom ; Orr, Nick ; Yu, Kai ; Chatterjee, Nilanjan ; Welch, Robert ; Hutchinson, Amy ; Crenshaw, Andrew ; Cancel-Tassin, Geraldine ; Staats, Brian J. ; Wang, Zhaoming ; Gonzalez-Bosquet, Jesus ; Fang, Jun ; Deng, Xiang ; Berndt, Sonja I. ; Calle, Eugenia E. ; Feigelson, Heather Spencer ; Thun, Michael J. ; Rodriguez, Carmen ; Albanes, Demetrius ; Virtamo, Jarmo ; Weinstein, Stephanie ; Schumacher, Fredrick R. ; Giovannucci, Edward ; Willett, Walter C. ; Cussenot, Olivier ; Valeri, Antoine ; Andriole, Gerald L. ; Crawford, E. David ; Tucker, Margaret ; Gerhard, Daniela S. ; Fraumeni, Joseph F. ; Hoover, Robert ; Hayes, Richard B. ; Hunter, David J. ; Chanock, Stephen J. / Multiple loci identified in a genome-wide association study of prostate cancer. In: Nature Genetics. 2008 ; Vol. 40, No. 3. pp. 310-315.
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AU - Thomas, Gilles

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AU - Wacholder, Sholom

AU - Orr, Nick

AU - Yu, Kai

AU - Chatterjee, Nilanjan

AU - Welch, Robert

AU - Hutchinson, Amy

AU - Crenshaw, Andrew

AU - Cancel-Tassin, Geraldine

AU - Staats, Brian J.

AU - Wang, Zhaoming

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AU - Fang, Jun

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AU - Berndt, Sonja I.

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AU - Feigelson, Heather Spencer

AU - Thun, Michael J.

AU - Rodriguez, Carmen

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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.

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