Association of a germ-line copy number variation at 2p24.3 and risk for aggressive prostate cancer.

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We searched for deletions in the germ-line genome among 498 aggressive prostate cancer cases and 494 controls from a population-based study in Sweden [CAncer of the Prostate in Sweden (CAPS)] using Affymetrix SNP arrays. By comparing allele intensities of approximately 500,000 SNP probes across the genome, a germ-line deletion at 2p24.3 was observed to be significantly more common in cases (12.63%) than in controls (8.28%); P = 0.028. To confirm the association, we genotyped this germ-line copy number variation (CNV) in additional subjects from CAPS and from Johns Hopkins Hospital (JHH). Overall, among 4,314 cases and 2,176 controls examined, the CNV was significantly associated with prostate cancer risk [odds ratio (OR), 1.25; 95% confidence interval (95% CI), 1.06-1.48; P = 0.009]. More importantly, the association was stronger for aggressive prostate cancer (OR, 1.31; 95% CI, 1.08-1.58; P = 0.006) than for nonaggressive prostate cancer (OR, 1.19; 95% CI, 0.98-1.45; P = 0.08). The biological effect of this germ-line CNV is unknown because no known gene resides in the deletion. Results from this study represent the first novel germ-line CNV that was identified from a genome-wide search and was significantly, but moderately, associated with prostate cancer risk. Additional confirmation of this association and functional studies are warranted.

Sun, Jishan (författare)
Li, Ge (författare)
Zhu, Yi (författare)
Zhang, Scott (författare)
Kim, Seong-Tae (författare)
Sun, Jielin (författare)
Wiklund, FredrikKarolinska Institutet (författare)
Wiley, Kathleen (författare)
Isaacs, Sarah D (författare)
Stattin, PärUmeå universitet,Urologi och andrologi(Swepub:umu)past0003 (författare)
Xu, Jianfeng (författare)
Duggan, David (författare)
Carpten, John D (författare)
Isaacs, William B (författare)
Grönberg, HenrikKarolinska Institutet (författare)
Zheng, S Lilly (författare)
Chang, Bao-Li (författare)
Karolinska InstitutetUrologi och andrologi (creator_code:org_t)

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