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
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 × 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.
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 × 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.
UR - http://www.scopus.com/inward/record.url?scp=39749118602&partnerID=8YFLogxK
U2 - 10.1038/ng.91
DO - 10.1038/ng.91
M3 - Article
C2 - 18264096
AN - SCOPUS:39749118602
SN - 1061-4036
VL - 40
SP - 310
EP - 315
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -