Researchers receive $12M NCI grant to identify biological pathways that lead to prostate cancer risk

Researchers at the USC Norris Comprehensive Cancer Center have received a $12 million National Cancer Institute (NCI) grant to lead a multi-institution international project aimed at identifying new biological pathways critical to the development and potential treatment of prostate cancer.

The Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) is a four-year grant that will bring together researchers from 13 institutions across the United States and Europe to identify common gene variants involved in the developmental progression of prostate cancer. Insight into prostate cancer biology will assist in the development of new targets for preventive and therapeutic interventions.

The grant is one of five awarded by the NCI for transdisciplinary research projects to exploit findings from existing genome-wide association studies (GWAS) and accelerate new discoveries.

Brian Henderson, M.D., distinguished professor of preventive medicine at the Keck School of Medicine of USC and Kenneth T. Norris, Jr. Chair in Cancer Prevention, will serve as principal investigator for the project.

"The overarching goal is to discover the pathways that drive prostate cancer development and to assess their role in clinical decision making," Henderson said.

Henderson and his colleague Christopher Haiman, Sc.D., associate professor of preventive medicine at the Keck School of Medicine, have been searching for potential genetic markers of prostate cancer within the African-American, Latino and Japanese populations of the Multiethnic Cohort (MEC) study.

The ELLIPSE program will be comprised of three integrated projects:

• Project 1 aims to take advantage of existing genome-wide association studies of prostate cancer in European, African-American, Latino and Japanese populations to discover new risk variants that may be associated with advanced disease and that contribute to ethnic differences in disease risk.

• Project 2 is focused on understanding the genes and biological mechanisms that the risk variants are acting through. Hypotheses will be systematically explored using a wide variety of established and emerging techniques.

• Project 3 will investigate the genetic basis of cancer susceptibility through gene-to-gene and gene-to-environment interactions, with a goal of providing new treatments and cancer prevention strategies.

Prostate cancer is the second most common cancer worldwide among men. Incidence rates are characterized by wide variation among racial and ethnic populations. For the past 15 years, Henderson—in collaboration with the Cancer Research Center of Hawaii—has headed the MEC study to evaluate genetic susceptibility to breast, prostate, colorectal and other cancers.

"We've come a long way in a short time. Until about five years ago we knew essentially nothing about prostate cancer's cause. Now we have identified regions in the genome where there is clear evidence of areas that influence prostate cancer risk," Henderson said. "With this new research collaboration we hope to move to the next step and look at how we can apply information to treatment and prevention to have a real impact on the disease."

The institutions involved in the project are:

University of Southern California
Harvard School of Public Health
University of Pennsylvania
University of Cambridge
The Institute of Cancer Research, Royal Marsden Hospital
Dana-Farber Cancer Institute
Columbia University
New York University
Duke University
Children's Hospital Boston
University of California, San Francisco
University of North Carolina at Chapel Hill
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