DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Studying the Role of Genetic Variants in Prostate Cancer Screening in High-Risk Men

Posted Apil 18, 2017

Veda N. Giri, M.D., Sidney Kimmel Cancer Center, Thomas Jefferson University

From Left to Right: Angelo De Marzo, M.D., Ph.D., Johns Hopkins University; Elizabeth Platz, M.P.H., Sc.D., Johns Hopkins University;  Karen Sfanos, Ph.D., Johns Hopkins University
Veda N. Giri, M.D., Sidney Kimmel Cancer Center, Thomas Jefferson University (photo provided by institution)

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in US men, and the prostate-specific antigen (PSA) test has been a primary method of screening for this disease. Population-wide PSA-based screening for PCa has been controversial. While PSA results may prompt unnecessary biopsies and overtreatment for many men, there may also be the detection of aggressive PCa. Men at high-risk for prostate cancer, such as African American men and men with a family history of PCa, may particularly benefit from progress in developing strategies for interpretation of PSA for screening. Prior PSA screening studies reporting inconsistent benefits to screening have not included a substantial proportion of high-risk men, leaving much to be learned regarding optimized early detection approaches in this high-risk population. While leading a PCa screening program of high-risk men, Dr. Veda Giri came to recognize the need to personalize PCa screening for these men in order to identify aggressive PCa while sparing other men from unnecessary biopsies.

With support from a FY08 Physician Research Training Award, Dr. Giri and her laboratory leveraged a prospective PCa screening study of high-risk men and evaluated the role of common genetic markers for PCa risk assessment. Through this work, she found that certain genetic markers at the chromosomal positions 8q and 17q could be indicative of earlier time to PCa diagnosis and could be useful in individualizing the interpretation of PSA screening results, thus potentially leading to personalized screening strategies in the future. Furthermore, with the emerging era of precision medicine focused on targeting therapies for cancers, understanding biologic processes linked to cancer initiation and progression is even more important. The preliminary tissue-based results of this project provided promising leads for future study regarding biologic pathways that may be important in PCa in high-risk men. Common genetic variants need further study before incorporation into PCa screening at this time.

This work and the career-development support of the Physician Research Training Award has spearheaded the way for Dr. Giri to advance her career and focus on developing the field of genetic counseling and genetic testing for men at high-risk of developing PCa. Dr. Giri is currently the Director of Cancer Risk Assessment and Clinical Cancer Genetics at Sidney Kimmel Cancer Center at Thomas Jefferson University, where she is leading a multi-institutional genetic testing study in the context of PCa to identify mutations informing risk for PCa.




Veda Model Figure 1: Research, patient-centered, and education initiatives led by Dr. Giri to advance personalized genetic evaluation and risk assessment for prostate cancer.









Publications:

Fleisher L, Davis SN, Gross L, et al. 2016. Lessons learned from implementing a prostate cancer risk assessment program for underserved high-risk men in the community: The Prostate REACH project. J Cancer Educ 31(1):191-197.

Handorf E, Crumpler N Gross L, et al. 2014. Prevalence of the HOXB13 G84E mutation among unaffected men with a family history of prostate cancer. J Genetic Counseling 23(3):371-376.

Hughes L, Ruth K, Rebbeck TR, et al. 2013. Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African American men. Prostate Cancer Prostatic Dis 16(4):308-314.

Chang BL, Hughes L, Chen DY, et al. 2013. Validation of association of genetic variants at 10q with PSA levels in men at high risk for prostate cancer. BJU Int 113(5b):E150-6.

Ishak M and Giri VN. 2011. A systematic review of replication studies of prostate cancer susceptibility genetic variants in high-risk men originally identified from genome-wide association studies. Cancer Epidemiol Biomarkers Prev 20(8):1599-1610.

Hall MJ, Ruth K, and Giri VN. 2012. Rates and predictors of colorectal cancer screening by race among motivated men participating in a prostate cancer risk assessment program. Cancer 118 (2):478-484.


Public and Technical Abstract:

Role of Genetic Variants at Chromosomal Loci 8q and 17q in Prostate Cancer Screening in African-American Men and Men With a Family History of Prostate Cancer


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Last updated Tuesday, April 18, 2017