Genetic alterations linked to excessive incidence of prostate most cancers in African American males
Prostate cancer tumors from African American men had a higher incidence of certain genetic changes that may be associated with aggressive diseases compared to prostate cancer tumors from white men.
Journal in which the study was published:
Molecular Cancer Research, a journal of the American Association for Cancer Research
Jianfeng Xu, DrPH, vice president of translational research at North Shore University HealthSystem and lead author on the study
“The incidence and mortality of prostate cancer are highest among African-American men, but the exact reasons for the inequality are not fully understood,” Xu said. “The inequality is likely due to several factors, including socioeconomic differences and biology. We suspect that differences in the genetic changes that occur within tumors may play a critical role.”
How the study was conducted and results:
In this study, Xu, along with lead author Wennuan Liu, PhD, and colleagues, sequenced 39 genes of tumor interest and adapted normal tissue from 77 African-American prostate cancer patients. They found that over 35 percent of these patients’ tumors had potentially harmful mutations in multiple genes, including the DNA repair genes ATM, BRCA2, and ZMYM3.
ZMYM3, which regulates chromatin and DNA repair, was found to be among the most common mutated genes in these patients. Nine of the 77 African American patients (11.7 percent) had tumors with mutations in ZMYM3, compared with 2.7 percent of the tumors in 410 white patients whose data was in the Genomic Data Commons database.
In addition, Xu and colleagues examined whether there were differences in the changes in copy number – when genetic material is gained or lost – between prostate tumors in African American and white patients. The researchers collected data on 171 African American patients and 860 white patients from several public databases.
They found marked changes in copy number between African American and white patients in the more aggressive, high-grade prostate tumors (Gleason score 7 or higher), but not in low-grade tumors. High-grade tumors in African American patients were more likely to have extra copies of the MYC oncogene and deletions of the LRP1B, MAP3K7, BNIP3L, and RB1 genes than tumors in white patients. The gain of MYC and the loss of MAP3K7 or RB1 were also associated with a more advanced tumor stage.
Our results suggest that marked genetic changes in prostate cancer in African American men compared to white men may contribute to more aggressive prostate cancer and lead to a higher mortality rate. When confirmed in other studies, these results not only help understand the racial differences in prostate cancer, but can also serve as a guide for personalized clinical management, such as predicting prognosis and guiding targeted therapy. “
Jianfeng Xu, DrPH, senior study author and vice president of translational research for North Shore University’s health system
Future work by Xu and colleagues will aim to understand how genetic changes in African American men affect recurrence, metastasis, treatment, and prostate cancer-specific death. They are also interested in developing tests to detect such genetic changes.
Limitations of the study include the small sample size, the use of different platforms to generate genetic data, and technical differences in sequencing between samples from African American men in this study and samples from white men in the Genomic Data Commons database.
American Association for Cancer Research