Could your ancestors impact your risk of prostate cancer?
A collaboration of scientists from the U.S. Department of Energy’s Argonne National Laboratory (IL, USA) and University of Southern California (CA, USA) have investigated the variations in prostate cancer risk across diverse genetic ancestries.
Besides skin cancer, prostate cancer is the most common cancer in men, with around one in eight men diagnosed during their lifetime. Prostate cancer is also the second-leading cause of cancer death.
Although there is a clear relationship between the risk of prostate cancer and an individual’s genetic makeup, there is still much we do not understand. Previous studies analyzing genetic ancestries and prostate cancer risk have commonly lacked representations among men of African, Hispanic and Asian ancestries, instead focusing on those of European ancestry.
To determine an individual’s risk of developing prostate cancer, we use a genetic risk score (GRS; an estimate of the contribution of genetic factors to a specific health outcome).
“You look at the genetic sequence and compare the variants that you find in the genetic sequence to the variants that are already found that have an impact on the particular disease. And then you calculate the risk for that particular person,” explained Ravi Madduri, a researcher at Argonne.
In the case of this study, the research group concentrated on single nucleotide polymorphisms (SNPs) to calculate the GRS of each participant. The researchers used genetic data from 156,319 prostate cancer cases and 788,443 control cases from the Million Veteran Program, one of the most extensive and diverse collections of genetic information in the world. This genetic data was analyzed for individual SNPs that contributed to prostate cancer risk, which were then combined to calculate the GRS.
Incredibly, the research group identified a total of 187 novel genetic markers that influence the risk of prostate cancer based on a specific ancestry. The study is also unique in employing the most recent advancements in high performance computing and AI techniques, which enabled the researchers to calculate risk variance for all participants in a short amount of time.
In this research, the number of cases from European ancestry grew by 43% compared to past studies, while those of Asian descent increased by 26%, African ancestry by 87%, and Hispanic groups by 45%. This increased representation of marginalized groups not only improved the accuracy of calculating prostate cancer risk posed by different ancestries, but also led to some novel findings. Notably, among the 451 current risk variants, men of African ancestry exhibited a heightened risk of aggressive prostate cancer compared to non-aggressive forms.
“This study not only provides more insight into the genetic architecture of people with African ancestry, but it also provides a large population that helps validate genetic findings from other populations,” Madduri commented.
