Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB21P

被引：199

作者：

Duggan, David ^{[1
]}

Zheng, Siqun L. ^{[3
]}

Knowlton, Michele

Benitez, Debbie ^{[1
]}

Dimitrov, Latchezar ^{[3
]}

Wiklund, Fredrik ^{[4
]}

Robbins, Christiane ^{[2
]}

Isaacs, Sarah D. ^{[5
]}

Cheng, Yu ^{[3
]}

Li, Ge ^{[3
]}

Sun, Jielin ^{[3
]}

Chang, Bao-Li ^{[3
]}

Marovich, Leslie ^{[1
]}

Wiley, Kathleen E. ^{[5
]}

Balter, Katarina ^{[4
]}

Stattin, Par ^{[6
]}

Adami, Hans-Olov ^{[4
,7
]}

Gielzak, Marta ^{[5
]}

Yan, Guifang ^{[5
]}

Sauvageot, Jurga ^{[5
]}

Liu, Wennuan ^{[3
]}

Kim, Jin Woo ^{[3
]}

Bleecker, Eugene R. ^{[3
]}

Meyers, Deborah A. ^{[3
]}

Trock, Bruce J. ^{[5
]}

Partin, Alan W. ^{[5
]}

Walsh, Patrick C. ^{[5
]}

Isaacs, William B. ^{[5
]}

Gronberg, Henrik ^{[4
]}

Xu, Jianfeng ^{[3
]}

Carpten, John D. ^{[2
]}

机构：

[1] Translat Genom Res Inst, Div Genet Basis Human Dis, Phoenix, AZ USA

[2] Translat Genom Res Inst, Div Integrat Canc Genom, Phoenix, AZ USA

[3] Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA

[4] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[5] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA

[6] Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden

[7] Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2007年 / 99卷 / 24期

关键词：

D O I：

10.1093/jnci/djm250

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background The consistent finding of a genetic susceptibility to Prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs 1571801, located in the DAB21P gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =.004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =.02). Conclusion A genetic variant in DAB21P may be associated with the risk of aggressive prostate cancer and should be evaluated further.

引用

页码：1836 / 1844

页数：9

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