Genome-wide association study of prostate cancer identifies a second risk locus at 8q24

Meredith Yeager, Nick Orr, Richard B. Hayes, Kevin B. Jacobs, Peter Kraft, Sholom Wacholder, Mark J. Minichiello, Paul Fearnhead, Kai Yu, Nilanjan Chatterjee, Zhaoming Wang, Robert Welch, Brian J. Staats, Eugenia E. Calle, Heather Spencer Feigelson, Michael J. Thun, Carmen Rodriguez, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein & 15 others Fredrick R. Schumacher, Edward Giovannucci, Walter C. Willett, Geraldine Cancel-Tassin, Olivier Cussenot, Antoine Valeri, Gerald L. Andriole, Edward P. Gelmann, Margaret Tucker, Daniela S. Gerhard, Joseph F. Fraumeni, Robert Hoover, David J. Hunter, Stephen J. Chanock, Gilles Thomas

Research output: Contribution to journalArticle

Abstract

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 × 10 -13; heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 × 10-11; rs6983267 P = 6.62 × 10-10). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).

Original languageEnglish (US)
Pages (from-to)645-649
Number of pages5
JournalNature Genetics
Volume39
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

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Genome-Wide Association Study
Prostatic Neoplasms
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Linkage Disequilibrium
Homozygote
Human Chromosomes
Genetic Predisposition to Disease
Heterozygote
Genetic Markers
Genetic Recombination
Case-Control Studies
Population
Neoplasms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Yeager, M., Orr, N., Hayes, R. B., Jacobs, K. B., Kraft, P., Wacholder, S., ... Thomas, G. (2007). Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nature Genetics, 39(5), 645-649. https://doi.org/10.1038/ng2022

Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. / Yeager, Meredith; Orr, Nick; Hayes, Richard B.; Jacobs, Kevin B.; Kraft, Peter; Wacholder, Sholom; Minichiello, Mark J.; Fearnhead, Paul; Yu, Kai; Chatterjee, Nilanjan; Wang, Zhaoming; Welch, Robert; Staats, Brian J.; 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.; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L.; Gelmann, Edward P.; Tucker, Margaret; Gerhard, Daniela S.; Fraumeni, Joseph F.; Hoover, Robert; Hunter, David J.; Chanock, Stephen J.; Thomas, Gilles.

In: Nature Genetics, Vol. 39, No. 5, 05.2007, p. 645-649.

Research output: Contribution to journalArticle

Yeager, M, Orr, N, Hayes, RB, Jacobs, KB, Kraft, P, Wacholder, S, Minichiello, MJ, Fearnhead, P, Yu, K, Chatterjee, N, Wang, Z, Welch, R, Staats, BJ, Calle, EE, Feigelson, HS, Thun, MJ, Rodriguez, C, Albanes, D, Virtamo, J, Weinstein, S, Schumacher, FR, Giovannucci, E, Willett, WC, Cancel-Tassin, G, Cussenot, O, Valeri, A, Andriole, GL, Gelmann, EP, Tucker, M, Gerhard, DS, Fraumeni, JF, Hoover, R, Hunter, DJ, Chanock, SJ & Thomas, G 2007, 'Genome-wide association study of prostate cancer identifies a second risk locus at 8q24', Nature Genetics, vol. 39, no. 5, pp. 645-649. https://doi.org/10.1038/ng2022
Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nature Genetics. 2007 May;39(5):645-649. https://doi.org/10.1038/ng2022
Yeager, Meredith ; Orr, Nick ; Hayes, Richard B. ; Jacobs, Kevin B. ; Kraft, Peter ; Wacholder, Sholom ; Minichiello, Mark J. ; Fearnhead, Paul ; Yu, Kai ; Chatterjee, Nilanjan ; Wang, Zhaoming ; Welch, Robert ; Staats, Brian J. ; 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. ; Cancel-Tassin, Geraldine ; Cussenot, Olivier ; Valeri, Antoine ; Andriole, Gerald L. ; Gelmann, Edward P. ; Tucker, Margaret ; Gerhard, Daniela S. ; Fraumeni, Joseph F. ; Hoover, Robert ; Hunter, David J. ; Chanock, Stephen J. ; Thomas, Gilles. / Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. In: Nature Genetics. 2007 ; Vol. 39, No. 5. pp. 645-649.
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abstract = "Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 × 10 -13; heterozygote odds ratio (OR): 1.26, 95{\%} confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95{\%} c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 × 10-11; rs6983267 P = 6.62 × 10-10). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21{\%} versus 9{\%}).",
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AU - Valeri, Antoine

AU - Andriole, Gerald L.

AU - Gelmann, Edward P.

AU - Tucker, Margaret

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AU - Chanock, Stephen J.

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