Prostate Cancer Predisposition Loci and Risk of Metastatic Disease and Prostate Cancer Recurrence

被引：40

作者：

Ahn, Jiyoung ^{[1
]}

Kibel, Adam S. ^{[3
,4
]}

Park, Jong Y. ^{[5
]}

Rebbeck, Timothy R. ^{[6
,7
]}

Rennert, Hanna ^{[2
]}

Stanford, Janet L. ^{[8
]}

Ostrander, Elaine A. ^{[9
]}

Chanock, Stephen ^{[10
]}

Wang, Ming-Hsi ^{[11
]}

Mittal, Rama D. ^{[13
]}

Isaacs, William B. ^{[12
]}

Platz, Elizabeth A. ^{[11
,12
]}

Hayes, Richard B. ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA

[2] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA

[3] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[5] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA

[6] Univ Penn, Sch Med, Ctr Biostat & Epidemiol, Philadelphia, PA 19104 USA

[7] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[8] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[9] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA

[10] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[11] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[12] Johns Hopkins Sch Med, Brady Urol Inst, Baltimore, MD USA

[13] Sanjay Gandhi Postgrad Inst Med Sci, Dept Urol, Lucknow, Uttar Pradesh, India

来源：

CLINICAL CANCER RESEARCH | 2011年 / 17卷 / 05期

关键词：

GENOME-WIDE ASSOCIATION; CHROMOSOME; 8Q24; SUSCEPTIBILITY VARIANTS; FUNCTIONAL-ANALYSIS; COMMON VARIANT; MULTIPLE LOCI; GENES; EXPRESSION; DIAGNOSIS; IMPLICATE;

D O I：

10.1158/1078-0432.CCR-10-0881

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain. Experimental Design: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights. Results: MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence. Conclusions: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants. Clin Cancer Res; 17(5); 1075-81. (C)2011 AACR.

引用

页码：1075 / 1081

页数：7

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