Similar to the role of BRCA 1 and 2 screening for prostate cancer risk, doctors can better help younger men at higher risk using a new test for the G84E mutation of the HOXB13 gene shown by Sunnybrook researchers to yield a 14-fold increase in prostate cancer risk in these men, compared for the first time within a larger group screened for the disease.
The HOXB13 gene has a key role in the development and functioning of the prostate gland. Its G84E mutation is associated with prostate cancer susceptibility.
"This new genetic test is one more tool in the arsenal, to potentially identify patients who may benefit from earlier or additional screening," says Dr. Robert Nam, lead investigator and urological oncologist, Genitourinary Cancer Care team, Sunnybrook's Odette Cancer Centre.
"For men with this gene mutation, especially younger men at higher risk, our goal is to extend lives as much as possible to their expected years of living through more proactive and better informed interventions," says Dr. Nam, associate professor, Department of Surgery, University of Toronto, and associate scientist, Sunnybrook Research Institute.
Published in the Journal of the National Cancer Institute, the study involved 4,068 men ages 40 to 94 years who underwent prostate biopsy to determine the presence of prostate cancer. The researchers identified and compared the frequency of HOXB13 mutations in the two groups: 1,843 men subsequently diagnosed with the disease (case subjects), and 2,225 men who were disease-free (control subjects).
Findings show the G84E mutation was 7 times more frequent in men of Caucasian descent who were diagnosed with prostate cancer (case subjects), compared to control subjects. Men who had early onset of the disease (at 55 years of age or younger) and or who had a family history, had an even stronger association of the G84E mutation with a prostate cancer risk of 14 times more likelihood, with the frequency of the mutation at 1 in 250. The carrier frequency for BRCA 1 and 2 mutations is about 1 in 300 to 1 in 800.
The researchers also recommend further study of a novel HOXB13 mutation, c.853delT which they found in men of African descent in the case and control groups. This mutation could also interfere with normal protein function of the HOXB13 gene and contribute to overgrowth or tumour formation in the prostate gland.
This study was generously funded by the Canadian Institute of Health Research, the National Cancer Institute of Canada, and the Ajmera Family Chair in Urologic Oncology.