Because a significant number of patients with prostate cancer (PCa) are diagnosed with disease unlikely to cause harm, genetic markers associated with clinically aggressive PCa have potential clinical utility.
FREE DAILY AND WEEKLY NEWSLETTERS OFFERED BY CONTENT OF INTEREST
Did you find this article relevant? Subscribe to UroToday-GUOncToday!
The fields of GU Oncology and Urology are advancing rapidly including new treatments, enrolling clinical trials, screening and surveillance recommendations along with updated guidelines. Join us as one of our subscribers who rely on UroToday as their must-read source for the latest news and data on drugs. Sign up today for blogs, video conversations, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.
Since cell cycle checkpoint dysregulation is crucial for the development and progression of cancer, we tested the hypothesis that common germ-line variants within cell cycle genes were associated with aggressive PCa.
Via a two-stage design, 364 common sequence variants in 88 genes were tested. The initial stage consisted of 258 aggressive PCa patients and 442 controls, and the second stage added 384 aggressive PCa Patients and 463 controls. European-American and African-American samples were analyzed separately. In the first stage, SNPs were typed by Illumina Goldengate assay while in the second stage SNPs were typed by Pyrosequencing assays. Genotype frequencies between cases and controls were compared using logistical regression analysis with additive, dominant and recessive models.
Eleven variants within 10 genes (CCNC, CCND3, CCNG1, CCNT2, CDK6, MDM2, SKP2, WEE1, YWHAB, YWHAH) in the European-American population and nine variants in 7 genes (CCNG1, CDK2, CDK5, MDM2, RB1, SMAD3, TERF2) in the African-American population were found to be associated with aggressive PCa using at least one model. Of particular interest, CCNC (rs3380812) was associated with risk in European-American cohorts from both institutions. CDK2 (rs1045435) and CDK5 (rs2069459) were associated with risk in the African-American cohorts from both institutions. Lastly, variants within MDM2 and CCNG1 were protective for aggressive PCa in both ethnic groups.
This study confirms that polymorphisms within cell cycle genes are associated with clinically aggressive PCa. Validation of these markers in additional populations is necessary, but these markers may help identify patients at risk for potentially lethal carcinoma. Prostate © 2015 Wiley Periodicals, Inc.
The Prostate. 2015 Dec 28 [Epub ahead of print]
Adam S Kibel, Jiyoung Ahn, Masis Isikbay, Aleksandra Klim, William S Wu, Richard B Hayes, William B Isaacs, E Warwick Daw
Division of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. , Division of Epidemiology, Department of Environmental Medicine, NYU School of Medicine, New York, New York. , Division of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. , Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri. , Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri. , Division of Epidemiology, Department of Environmental Medicine, NYU School of Medicine, New York, New York. , Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland. , Departments of Genetics, Washington University School of Medicine, St. Louis, Missouri.