TY - JOUR
T1 - Genome-wide association study of prostate cancer identifies a second risk locus at 8q24
AU - Yeager, Meredith
AU - Orr, Nick
AU - Hayes, Richard B.
AU - Jacobs, Kevin B.
AU - Kraft, Peter
AU - Wacholder, Sholom
AU - Minichiello, Mark J.
AU - Fearnhead, Paul
AU - Yu, Kai
AU - Chatterjee, Nilanjan
AU - Wang, Zhaoming
AU - Welch, Robert
AU - Staats, Brian J.
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 - Cancel-Tassin, Geraldine
AU - Cussenot, Olivier
AU - Valeri, Antoine
AU - Andriole, Gerald L.
AU - Gelmann, Edward P.
AU - Tucker, Margaret
AU - Gerhard, Daniela S.
AU - Fraumeni, Joseph F.
AU - Hoover, Robert
AU - Hunter, David J.
AU - Chanock, Stephen J.
AU - Thomas, Gilles
N1 - Funding Information:
The HPFS study is supported by NIH grants CA CA55075 and 5U01CA098233-04. The ACS study is supported by U01 CA098710. The ATBC study is supported by NIH contracts N01-CN-45165, N01-RC-45035 and N01-RC-37004. F.R.S. is supported by an NRSA training grant (T32 CA 09001). P.F. is supported by a UK Engineering and Physical Sciences Research Council Grant (GR/S18786). M.M. is supported by the Wellcome Trust. N.O., R.B.H., S.W., K.Y., N.C., M.T., J.F.F., R.H., S.J.C. and G.T. are supported by the Intramural Research Program of the National Cancer Institute (US National Institutes of Health, Department of Health and Human Services).
PY - 2007/5
Y1 - 2007/5
N2 - 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%).
AB - 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%).
UR - http://www.scopus.com/inward/record.url?scp=34247548755&partnerID=8YFLogxK
U2 - 10.1038/ng2022
DO - 10.1038/ng2022
M3 - Article
C2 - 17401363
AN - SCOPUS:34247548755
SN - 1061-4036
VL - 39
SP - 645
EP - 649
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -