Monash University’s Precision Medicine research group has discovered multiple new genetic risk factors that make men susceptible to aggressive prostate cancer, in a landmark study that will contribute to future prevention of the disease.

The work is the product of decades of collaborative research conducted by the Precision Medicine group and the Cancer Epidemiology Division of Cancer Council Victoria.

“This research is very important to our efforts to discover modifiable lifestyle factors that might influence a man’s future risk of developing aggressive prostate cancer,” said Associate Professor Robert MacInnis, Principal Research Fellow at Cancer Council Victoria.

Reported in a series of articles published in the prestigious international journals European Urology, Journal of the National Cancer Institute and International Journal of Cancer, the research involved national and international collaborators and used the latest genetic sequencing technologies to screen thousands of men with and without prostate cancer.

The team also contributed a large amount of resources to a complementary international study of genetic risk factors for prostate cancer that analysed the DNA repair genes from 5,545 men with aggressive and non-aggressive prostate cancer.

Led by Dr Tu Nguyen-Dumont, the research group used gene panel sequencing to compare the genetic variants of 787 Australian men with aggressive prostate cancer and 769 men with non-aggressive prostate cancer.

Further research compared gene variations in 920 men with either a strong family history of prostate cancer or the aggressive form of the disease. This work utilised whole exome sequencing to discover ten new genes associated with prostate cancer risk, with all but two of these connected with the aggressive form.

Together, the outcomes of these studies validate that pathogenic variants in BRCA2, PALB2 and ATM are associated with prostate cancer risk in men with a strong family history and risk of aggressive disease.

“Our findings contribute important evidence to support the clinical interpretation of genetic variation and the identification of the men at greatest risk of developing the disease,” Dr Nguyen-Dumont observed.

“This new data will improve the care of men with and without prostate cancer, including the ability to predict susceptibility to aggressive prostate cancer and put in place measures to mitigate or even prevent the disease,” Dr Nguyen-Dumont added.

“Together these results provide important evidence upon which to further advance precision prevention for prostate cancer,” said Professor Melissa Southey, Chair of Precision Medicine at Monash University and Research Director of the MPCCC.