Two Genome-wide Association Studies of Aggressive Prostate Cancer Implicate Putative Prostate Tumor Suppressor Gene DAB2IP

• Published in: JNCI : Journal of the National Cancer Institute 2007-12, Vol.99 (24), p.1836-1844
• Main Authors: Duggan, David, Zheng, Siqun L., Knowlton, Michele, Benitez, Debbie, Dimitrov, Latchezar, Wiklund, Fredrik, Robbins, Christiane, Isaacs, Sarah D., Cheng, Yu, Li, Ge, Sun, Jielin, Chang, Bao-Li, Marovich, Leslie, Wiley, Kathleen E., Bälter, Katarina, Stattin, Pär, Adami, Hans-Olov, Gielzak, Marta, Yan, Guifang, Sauvageot, Jurga, Liu, Wennuan, Kim, Jin Woo, Bleecker, Eugene R., Meyers, Deborah A., Trock, Bruce J., Partin, Alan W., Walsh, Patrick C., Isaacs, William B., Grönberg, Henrik, Xu, Jianfeng, Carpten, John D.
• Format: Article
• Language: English
• Subjects: adult; African American; African Americans; African Americans - genetics; Aged; allele; Biological; Biomarkers, Tumor - genetics; cancer risk; case control study; Case-Control Studies; Caucasian; controlled study; dab2ip gene; DAB2IP protein; European Continental Ancestry Group; European Continental Ancestry Group - genetics; gene; gene location; Genes; Genes, Tumor Suppressor; genetic association; genetic code; genetic marker; genetic model; genetic predisposition; Genetic Predisposition to Disease; Genetic research; genetic susceptibility; genetic variability; genetics; Genomics; Genotype; guanosine triphosphatase activating protein; human; Humans; major clinical study; Male; Middle Aged; Odds Ratio; Oncology; Polymorphism; Polymorphism, Single Nucleotide; population research; priority journal; Prostate cancer; prostate tumor; Prostatic Neoplasms; Prostatic Neoplasms - genetics; ras GTPase-Activating Proteins; ras GTPase-Activating Proteins - genetics; risk; Risk Assessment; risk factor; Risk Factors; Single Nucleotide; single nucleotide polymorphism; statistical significance; suppressor gene; Sweden; tumor marker; Tumor Markers; Tumor Suppressor; tumor suppressor gene; unclassified drug
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djm250

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