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From the Summer/Fall 2015 Quest
Genetic research examines connections in human biology. This field has the opportunity to individualize prostate cancer screening and treatment. © Dan Oldfield
There is a strong genetic predisposition to prostate cancer, and many scientific studies have identified rare genetic variants that increase the risk of prostate cancer and aggressive forms of the disease. Using these genetic variants to stratify individual patients for prostate cancer risk could improve and personalize prostate cancer screening and treatment.

Using Genetics to Prevent Delayed Biopsies in African American Men

Dr. Catalona and other researchers conducted a study to evaluate whether genetic correction using genetic variants could reduce potentially unnecessary and/or delayed biopsies in African-American men.

Certain genetic variants have been shown to be associated with PSA. Researchers compared genotypes of four of these variants between 964 Caucasian and 363 African-American men without known prostate cancer. Researchers adjusted PSA values based on each man's individual carrier status for the genetic variants, then calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥2.5 or ≥4.0 ng/ml) before and after genetic correction.

Genetic correction resulted in an increased proportion of African- American men crossing the threshold for biopsy (2.5% and 3.9%, based on the biopsy threshold level). These results raise the question of whether genetic differences in PSA might contribute to delayed prostate cancer diagnoses in African-American men.

Donin NM, Loeb S, Cooper PR, Roehl KA, Baumann NA, Catalona WJ, Helfand BT. Genetically adjusted prostate-specific antigen values may prevent delayed biopsies in African- American men. BJU Int. 2014 Dec;114(6b):E50-5. doi: 10.1111/bju.12647. Epub 2014 Jul 15.

Genetic Modifiers of Prostate Cancer in Native American Men

Researchers in the Partnership for Native American Cancer Prevention (PNACP) are currently studying the genetics of prostate cancer in Native Americans.

Studies have indicated that prostate cancer is heritable, suggesting a link between genetics and risk level. Less Native American men have prostate cancer than Hispanic and European American men. However, rates of prostate cancer mortality are similar among the groups. Among Navajo and Northern Plains Indian men, prostate cancer mortality is higher than the U.S. rate, and at diagnosis men in this group generally had cancer at a higher grade and stage than European American men.

There are some social and economic factors that could affect the higher rate of prostate cancer in Native American men. However, PNACP researchers are examining the differences in tumor biology and/or genetic aspects between the groups that could contribute to more aggressive disease and poor outcomes for Native Americans diagnosed with prostate cancer.

Specifically, the scientists are investigating genetic variations in tumor suppressor genes and their pseudogenes that alter microRNA target sites. miRNAs are critical regulators of cellular functions. They are examining a novel class of genetic variation for new determinants of cancer recurrence and survival in certain RNA networks. The also hope to identify uniquely Native American DNA sequence variations affecting tumor suppressor gene function and test these for associations with prostate cancer.

The goal of the project is to translate an understanding of prostate cancer progression mechanisms into the identification of new biomarkers that identify aggressive features of the disease.

The PNACP is the collaboration between the University of Arizona Cancer Center, Northern Arizona University, the National Institute of Health and the National Cancer Institute. The program's aim is to alleviate the unequal burden of cancer among Native Americans of the Southwest through research, training and outreach. In January, Dr. Catalona served as an expert scientific advisor to provide scientific guidance, feedback and advice to the principal investigators and project leaders of the group's current research project.

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