A world research team led by scientists within the Center for Genetic Epidemiology on the Keck School of Medicine of USC and USC Norris Comprehensive Cancer Center has singled out mutations in 11 genes which can be related to aggressive types of prostate cancer. These findings come from the largest-scale prostate cancer study ever exploring the exome -; that’s, the important thing sections of the genetic code that contain the instructions to make proteins. The scientists analyzed samples from about 17,500 prostate cancer patients.

Today, oncologists customize look after certain individuals with aggressive prostate cancer with help from genetic tests. The outcomes can inform treatment, as one class of targeted therapies has proved effective against some inherited prostate cancers. Test findings can also result in genetic screening amongst patients’ relations, so that they have the prospect to take measures that reduce risk and to work with their doctors to be more vigilant in early detection.

The study, published in JAMA Oncology, uncovered mutations related to higher risk for more-aggressive, deadlier prostate cancer that aren’t currently included on genetic test panels. The researchers also found some genes which can be currently a part of such panels aren’t linked with risk for aggressive disease.

Very large studies are needed to tell the creation of gene panels used for testing. A number of the genes in these panels were based on small studies and weren’t related to prostate cancer in our study. We also found evidence that other genes perhaps should be added. The outcomes aren’t completely definitive, however it’s clear that more work must be done to find out which genes oncologists should concentrate on in testing.”

Christopher Haiman, ScD, corresponding creator holder of the AFLAC Chair in Cancer Research and professor of Population and Public Health Sciences on the Keck School of Medicine

Exploring prostate cancer genes in 17,500 patients

Combining information from 18 studies conducted within the U.S., Europe and Australia, the research team analyzed blood samples from prostate cancer patients of European descent, 9,185 of whom had aggressive disease and eight,361 who didn’t and compared the frequency of mutations among the many two groups.

In the primary stage of their investigations, Haiman and his colleagues sequenced your entire set of protein-coding genes amongst almost a 3rd of participants. Within the second stage, the researchers used samples from the remaining participants to zoom in on a subset of 1,749 genes that either had previously been related to cancer or showed up as likely candidates in the primary phase.

That subset included almost 200 genes involved with DNA repair. When that process is disrupted, it creates a chance for cancerous cells to arise and take hold.

A chance to advance treatment and prevention

The eleven genes that emerged as having mutations significantly linked to aggressive prostate cancer include BRCA2, also known for its connection to breast cancer. The list of genes, in addition to those currently screened in genetic tests found to not be linked serious disease, could influence individualized treatment for prostate cancer, in addition to screening.

Haiman notes that mutations present in the study also showed up in some patients who did not have aggressive disease.

“This implies that mutations in these people may put them at greater risk for his or her cancer later becoming more advanced,'” he said. “While screening is concentrated on men with advanced disease or a family history, finding patients with less advanced disease who carry these genetic variants may enable them to receive targeted types of treatment earlier on.”

The study does include two essential caveats. One is that, despite its large size, some mutations that drive risk for aggressive prostate cancer are so rare that even greater studies are needed to clear up the image. The opposite limitation is that the findings may differ outside of the population under investigation, people of European descent.

“It would be essential for similar efforts to happen in men of African ancestry,” said Haiman, who can also be co-leader of the Cancer Epidemiology Program at USC Norris cancer center. “That is very essential. These genes and maybe others could also be essential, so additional work must be done in other populations.”

About this study

The primary creator of the study is Burcu Darst, PhD, an assistant professor at Fred Hutchinson Cancer Center and former postdoctoral research associate on the Keck School. Other co-authors from the Keck School are Xin Sheng, MS; Peggy Wan, MA; Loreall Pooler, BS; Lucy Xia, MS; and David Conti, PhD, a professor of Population and Public Health Sciences. The greater than two dozen other co-authors of the study comprise researchers from the Institute of Cancer Research, London; the National Cancer Institute; the American Cancer Society; the University of Cambridge, the University of Oxford and the Royal Marsden NHS Foundation Trust, all within the UK; University of Texas MD Anderson Cancer Center; the Mayo Clinic; the Karolinska Institute in Sweden; the Cancer Council Victoria, Monash University and the University of Melbourne, all in Australia; Dana-Farber Cancer Institute; Aarhus University in Denmark; Northwestern University; and Johns Hopkins University.

This study was supported by the National Institutes of Health (R01CA196931, R00CA246063) and the Andy Hill CARE Foundation.