The genetic landscape of prostate cancer susceptibility in Africa is, like the continent itself, a picture of sweeping diversity, the largest study of the phenomenon concludes. 

The findings, published in the journal Nature Genetics, are an important step in unravelling why prostate cancer rates are highest in men of African descent, whether they live in Africa itself, the United States, or elsewhere. They also demonstrate that studies of largely homogenous populations may not capture the full complexity of inherited cancer risk, the study authors say. 

“We know that prostate cancer has a very strong genetic component. In fact, genes probably explain more of the incidence — the overall occurrence — of prostate cancer than any other factor,” says Dana-Farber’s Timothy Rebbeck, PhD, the co-senior author of the study with Joseph Lachance, PhD, of the Georgia Institute of Technology. 

“In the United States, the incidence rates of prostate cancer per 100,000 men are 119.2 for European Americans and 197.9 for African Americans. For this study, we wanted to explore whether an underlying genetic susceptibility to prostate cancer — such as has been found in African American men — exists in African men as well.” 

Eurocentric research

Research has uncovered more than 450 germline variants — inherited DNA changes — associated with an increased risk of prostate cancer. Most of these studies, however, have focused on individuals of European descent. 

For the new study, researchers analyzed DNA from nearly 7,500 men from Senegal, Nigeria, Ghana, Uganda, and South Africa — 3,963 of whom had prostate cancer and 3,509 who didn’t — looking for genetic differences between the two groups. To determine if the genetic underpinnings of prostate cancer varied from one region to another, they compared findings from West, East, and South Africa. 

They found 15 risk factors — genetic changes that heightened the chances of developing prostate cancer — at three locations in the genome. Four of the 15 had not previously been tied to prostate cancer risk. 

In some ways, these results reaffirmed previous research. The three sites where the risk factors were found — dubbed 8q24.21, 6q22.1, and 11q13.3 for their places on the map of the human genome — are well-known among scientists as hotbeds of prostate cancer risk. 

Interestingly, the sequences of DNA at these sites are not part of any gene. That is, they don’t contain the code for cell proteins but play a regulatory role, helping control how much of those proteins get made. 

The study also found that the “genetic architecture” of prostate cancer differs across Africa. While certain genetic variations are more common in some regions of the continent than others, the biggest regional differences have to do with the magnitude of the effect of those variations. Prostate cancers in East and South Africa, say, may be associated with a similar set of genetic changes — call them variations A, B, C, and D. But in East Africans, variations A and C, for example, may raise the risk of prostate cancer more than they do in South Africans. 

Six of the 15 prostate cancer-related variations identified in the study are “private to Africa” — that is, found almost exclusively in current African populations, not in people of African ancestry who live in Europe or the United States. Some of the variations in people in East and South Africa, for example, are largely absent from the genomes of African Americans. 

“Due to the historical legacy of the trans-Atlantic slave trade, African Americans are genetically similar to the West African subset of our data,” Rebbeck relates. “However, one key difference between African and African American populations is that African Americans’ genome contains an admixture of European and Native American ancestry. African Americans also experience substantively different lifestyles and environmental exposures than individuals living in sub-Saharan Africa, which may help account for differences in prostate cancer incidence between these populations.” 

The study findings underscore the benefits of conducting genetic studies in diverse, understudied populations, the authors write.

“Knowing the full spectrum of genomic changes associated with prostate cancer risk is an important step toward creating treatments that will be broadly effective,” Rebbeck states.