World-first study uncovers potential DNA secrets of prostate cancer in African men
Professor Vanessa Hayes
24 October 2018
The pilot research study, which was conducted on a small cohort, shows prostate cancer in Africans is potentially different to elsewhere in the world, and needs attention to find a better way to detect and treat it.
The research, published in Cancer Research1 was led by Professor Vanessa Hayes at the Garvan Institute of Medical Research and the University of Sydney, in collaboration with St Vincent’s Hospital, as well as the Universities of Limpopo and Pretoria in South Africa.
In Africa, prostate cancer DNA looks different
Prostate cancer is particularly lethal in Africa. Within five years of diagnosis, five in 20 African men will lose their lives2, compared to one in 20 Australian men3. Risk factors for the disease are well known – and include age, family history of the disease and African ancestry. The link to African ancestry has, however, been largely overlooked – until now.
Prostate cancer is a genetic disease. The secrets to better understanding cancer and improving treatment and diagnosis lie in the DNA of both the cancer tumours, and the germ-line of those who carry them.
As cancer progresses, it acquires ‘mutations’ or DNA changes, some of which drive cancer growth and ultimately metastatic disease. Unlike other adult cancers, current data classifies prostate cancer as having a low tumour mutational burden – that is, relatively few DNA changes within tumour cells.
However, Professor Hayes and her team have discovered that prostate tumours in African men have more DNA changes than non-African counterparts. The six African prostate tumours they analysed had, on average, a doubling of mutational burden than a comparative group of nine prostate tumours from Australian men of European ancestry.
Along with the higher mutational burden, there was also a higher level of ‘tumour driver mutations’, changes in the DNA that drive cancer and make it more aggressive, and a striking absence of commonly observed non-African tumour mutational signatures.
Does the African prostate tumour genome signature point to an unknown carcinogen?
The substantial DNA differences between African and European prostate tumours raise an important question – why? Is there a reason why prostate cancer is so aggressive in Africa, and can the DNA differences help us uncover it?
“Usually, we see a higher tumour mutation burden in cancers with a carcinogenic cause – like UV exposure causing melanoma, or cigarettes and lung cancer,” explains Professor Hayes. “The elevated tumour mutational burden observed in our study, may therefore be explained by an as yet unknown carcinogenic agent contributing to aggressive prostate cancer presentation in Africa.”
Professor Riana Bornman from the University of Pretoria has been searching for modifiable environmental risk factors contributing to aggressive disease across southern Africa.
“If we could determine what that carcinogen might be, there would be the opportunity for public health interventions to limit exposure – and, we hope, decrease the aggressiveness of African prostate cancer,” says Professor Bornman.
The benefit of direct population comparisons
According to Dr Weerachai Jaratlerdsiri, Research Officer at Garvan, understanding the role of African ancestry in the development of prostate cancer could not only improve the way the disease is treated in Africa, but globally this study will improve our understanding of aggressive and non-aggressive disease.
“What sets this data apart is that the samples from both Africa and Australia were processed through the same pipeline, ensuring comparability in the results. All the samples, 6 from Africa and 9 from Australia were from patients presenting with aggressive prostate cancer who had as yet not undergone treatment,” says Dr Jaratlerdsiri.
Prostate cancer in Africa in the era of personalised medicine
Next, Professor Hayes and her team will validate their pilot study by sequencing a minimum of 100 African prostate cancer genomes, while they are expanding their research efforts across Africa.
Professor Hayes says the new findings are an important reminder that a range of ethnicities should be taken into account, as we enter an era of personalised medicine. While it has been well established that men of African ancestry are at greater risk than any other ethnic group to die from prostate cancer, the link to Africa has been overlooked – until now.
“Our findings suggest that treatment for prostate cancer should perhaps be different in Africa than it is elsewhere in the world. That kind of insight is only possible because we’re looking at genomic information from a range of different populations.”
“It’s crucial that we continue to explore how our genetic ancestry might affect our response to treatments, so that the full benefits of personalised medicine reach as many people as possible,” says Professor Hayes.
New possibilities for prostate cancer treatment in Africa
Immunotherapy, a relatively new style of cancer treatment that boosts the body's immune system to fight cancer, has been particularly effective in cancers with a high tumour mutational burden and a carcinogenic cause, such as melanoma.
“While immunotherapy hasn’t been overly successful as a treatment for prostate cancer to date, the significant DNA differences between African prostate tumours and those without an African ancestry, suggest potential for treatment for African men,” says Professor Hayes.
We would like to acknowledge our generous funders and collaborators The Petre Foundation, PROMIS, Movember, Prostate Cancer Foundation Australia, Cancer Association of South Africa and Australian Prostate Cancer Research Centre New South Wales.
- Jaratlerdsiri, W., Chan, E. K. F., Gong, T., Petersen, D. C., Kalsbeek, A. M. F., Venter, P. A., Stricker, P.D., Bornman, M.S.R., Hayes, V. M. (2018). Whole Genome Sequencing Reveals Elevated Tumor Mutational Burden and Initiating Driver Mutations in African Men with Treatment-Naïve, High-Risk Prostate Cancer. Can Res. doi:10.1158/0008-5472.CAN-18-0254
- Tindall EA, Monare LR, van Zyl S, Petersen DC, Hardie R-A, Segone AM, Venter PA, Bornman MSR, Hayes VM. Clinical presentation of prostate cancer in Black South Africans. The Prostate, (2014) 74(8):880-91.
- Cancer Australia: www.prostate-cancer.canceraustralia.gov.au/statistics