Researchers have found that prostate cancer tumours from African American men harboured higher frequencies of distinct genetic alterations that may be associated with aggressive disease.
Prostate cancer
November (also known as ‘Movember’) marks the month of prostate cancer awareness. Every year many men grow (or try to grow) their facial hair to raise awareness of men’s health issues. There are around 50,000 new cases of prostate cancer every year. Incidence varies widely between different ethnic populations and countries. Research has shown that the incidence and mortality of prostate cancer is higher among African American men. The exact mechanism behind this disparity is not clear. However, experts suggest it is likely due to multiple factors, including socioeconomic differences and biology. Researchers also suspect that underlying differences, such as genetic susceptibility, may contribute to this disparity.
Distinct genetic alterations
In a study, published in Molecular Cancer Research, researchers sequenced 39 genes of interest in tumours and matched normal tissue, from 77 African American patients with prostate cancer. The team found that over 35% of patients’ tumours harboured potentially damaging mutations in several genes. This specifically included the DNA repair genes ATM, BRAC2 and ZMYM3, among others. ZMYM3 (regulates chromatin and DNA repair) was the most frequently mutated gene in these patients. Specifically, 11.7% of patients had tumours with mutations in this gene.
The team also examined whether there were differences in copy number alterations between prostate tumours of African American and White patients. To do this, they pooled data representing 171 African American patients and 860 White patients from several public databases. From this, they found distinct copy number alterations in more aggressive, high-grade prostate tumours between the two groups. African American patients were more likely to have additional copies of the MYC oncogene in high-grade tumours. They were also more likely to carry deletions of the LRP1B, MAP3K7, BNIP3L and RB1 genes.
Future
The team hope to continue this work by exploring how genetic alterations in African American men affect recurrence, metastasis, treatment and prostate cancer-specific death. Moreover, they are also interested in developing tests to detect these changes.
Dr. Jianfeng Xu, Vice President of Translational Research at NorthShore University HealthSystem and senior author of the study, stated:
“Our findings suggest that distinct genetic alterations in the prostate cancers of African American men, in comparison to White men, may contribute to more aggressive prostate cancer and could lead to a higher mortality rate.
If confirmed in other studies, these results will not only help to understand the racial disparity of prostate cancer but could also help guide personalised clinical management, such as predicting prognosis and guiding targeted therapy.”
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