Researchers from the US and Sweden have for the first time identified a gene variant that is linked with aggressive prostate cancer, adding weight to the idea that patients’ genetic information will one day help decide treatment decisions.
The study was published online before print in the Proceedings of the National Academy of Sciences, PNAS, and is the work of lead author Dr Jianfeng Xu, professor of epidemiology and cancer biology at Wake Forest University Baptist Medical Center in Winston-Salem, North Carolina, US and colleagues, including some based at other research establisments in the US and Sweden.
The authors wrote that prostate cancer accounts for a quarter of all cancers diagnosed in the US, and although most men who develop it have the slow-growing form, aggressive prostate cancer is the second leading cause of cancer death among male Americans, with over 27,000 dying every year from the disease.
Studies using autopsy exams suggest that most aging men will develop lesions in their prostate that would be diagnosed as cancer if detected clinically.
Xu said that not being able to tell the difference between life-threatening, aggressive prostate cancer and the slow-growing non-threatening form is a big problem in deciding treatments.
Previous studies, including some done by Xu and his team, have found several genetic variants linked to the risk of developing prostate cancer, but this is the first study to find one linked to the aggressive form of the disease.
Xu told the press that this discovery:
“Addresses one of the most important clinical questions of prostate cancer – the ability at an early stage to distinguish between aggressive and slow-growing disease.”
Current evidence suggests that some men are genetically predisposed to developing the aggressive form of the disease, so Xu and colleagues thought they would test the idea that such men have inherited genetic variants that could be used as markers to help early early identification and thus increase the chance of curing the cancer at an early stage.
For the study, the researchers analysed genetic information from 4,849 men with aggressive prostate cancer and 12,205 with the slow-growing form of the disease to look for common genetic variants among the former that were not present in the latter.
The genetic information came from men taking part in the National Cancer Institute (NCI) Genetic Markers of Susceptibility study plus other study populations in the US and Sweden. The NCI was the main sponsor of this study.
The researchers found that one variant, rs4054823, was linked to a 25 per cent higher risk of developing aggressive prostate cancer.
Xu explained that while a single variant with a moderate effect is unlikely to be enough to predict risk, the finding establishes the principle that they exist, and there is a strong chance there are more in the genome: it’s just a case of finding them.
The researchers expect one day there will be a panel of variants, thus aiding the development of a screening approach whereby fewer men would need screening, which would reduce over-diagnosis, and also increase the chance of finding men with the aggressive disease at an early stage and improve their chances of being cured.
Co-author Dr Karim Kader, a Wake Forest Baptist urologist specializing in prostate cancer said:
“Identifying factors that are associated with a risk of having or developing aggressive disease is urgently needed to reduce over-diagnosis and over-treatment of this common cancer.”
“Inherited genetic variant predisposes to aggressive but not indolent prostate cancer.”
Jianfeng Xu, Siqun Lilly Zheng, Sarah D. Isaacs, Kathleen E. Wiley, Fredrik Wiklund, Jielin Sun, A. Karim Kader, Ge Li, Lina D. Purcell, Seong-Tae Kim, Fang-Chi Hsu, Pär Stattin, Jonas Hugosson, Jan Adolfsson, Patrick C. Walsh, Jeffrey M. Trent, David Duggan, John Carpten, Henrik Grönberg and William B. Isaacs.
PNAS, published online before print 11 January 2010.
DOI:10.1073/pnas.0914061107
Source: Wake Forest University Baptist Medical Center.
Written by: Catharine Paddock, PhD