NatureGenetics2月10日：前立腺癌SNPs一挙に三報

Published online: 10 February 2008 | doi:10.1038/ng.91

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

• 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 HNF1BTCF2 on 17q); P <>-10). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < src="http://www.nature.com/__chars/math/special/times/black/med/base/glyph.gif" style="border: 0pt none ; vertical-align: middle;" alt="times"> 10^-13 and P < src="http://www.nature.com/__chars/math/special/times/black/med/base/glyph.gif" style="border: 0pt none ; vertical-align: middle;" alt="times"> 10^-6). Loci on chromosome 10 include MSMB, which encodes -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 < src="http://www.nature.com/__chars/math/special/times/black/med/base/glyph.gif" style="border: 0pt none ; vertical-align: middle;" alt="times"> 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.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.

Published online: 10 February 2008 | doi:10.1038/ng.90

Multiple newly identified loci associated with prostate cancer susceptibility

• Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at 60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (<0.5 style="color: rgb(153, 0, 0); font-weight: bold;">chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 10^-8 to P = 8.7 10^-29). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3.

The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.

Nature Genetics
Published online: 10 February 2008 | doi:10.1038/ng.89

Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer

• We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 10^-13 10^-9, respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease.

deCODE genetics, 101 Reykjavik, Iceland.