A new study has reported that Black men have a range of genetic alterations that increase their risk of developing prostate cancer compared to their White or Asian counterparts.
Prostate cancer is a highly heritable disease. The incidence varies dramatically across ancestry groups. It is approximately 75% higher in African Americans and 45% lower in Asians, compared with non-Hispanic Whites. The most well established risk factors for prostate cancer include age, family history and germline variation. As much as 57% of the variability in prostate cancer risk is due to genetic factors. Accordingly, it is thought that genetic factors, at least in part, contribute to the population disparities seen in incidence. However, genome-wide association and fine-mapping studies have been conducted mainly in populations of European ancestry.
Genetic changes identified
The study, published in Nature Genetics, was the largest and most ethnically diverse genetic analysis of prostate cancer. A team of international researchers, led by scientists at The Institute of Cancer Research (ICR) and The University of Southern California, pooled data from 17 large-scale studies from around the world. They analysed the genetics of more than 200,000 men of European, African, Asian and Hispanic ancestry.
The team identified 86 new genetic risk variants independently associated with prostate cancer risk. This brought the total of known risk variants to 269. These genetic variants individually have a small effect on the risk of developing cancer. However, when combined they can substantially increase an individuals risk. As a result, the researchers developed an overall genetic risk score (GRS) to identify men who have the highest levels of inherited risk. Men of African ancestry were found to have a mean GRS that was 2.18-times higher than men of European ancestry. Conversely, men of East Asian ancestry had a 0.73-times lower risk than men of European ancestry.
These findings support the role of germline variation contributing to population differences in cancer risk. Most importantly, the use of GRS offers an approach for personalised risk prediction. Researchers could use this approach in the future to identify men who need targeted screening.
Professor Paul Workman, Chief Executive of the ICR, stated:
“It is great to see how our increasing knowledge of cancer genetics can guide targeted methods for early detection. We have known for some time that the incidence of prostate cancer is higher among Black men, but what this study does is uncover a key underlying cause of that disparity, so that we can design new screening and treatment strategies to address it. I hope this research can play an important role in reducing health inequalities among men with prostate cancer, by allowing Black men and others at high genetic risk to be identified and treated earlier.”
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