Genetic changes associated with a high incidence of prostate cancer in African-American men

Review by Emily Henderson, Bachelor of ScienceOctober 28, 2020

Conclusion:

Prostate cancer tumors in African-American men had a higher frequency of certain genetic changes that may be associated with progressive disease than prostate cancer tumors in white men.

Journals where research was Ppblished:

Molecular cancer research, Journal of the American Association for Cancer Research

Author:

Jianfeng Xu, DrPH, Vice President of Translational Research for Health Systems, North Shore University, Senior Author of Research

Background:

“Prostate cancer incidence and mortality are highest among African-American men, but the exact reason for the inequality is not fully understood,” Xu said. “This disparity can be due to multiple factors, including socio-economic differences and biology. Differences in genetic alterations that occur within the tumor can play an important role. . “

Survey implementation method and results:

In this study, Xu, along with lead authors Wennuan Liu, PhD and colleagues, sequenced 39 genes of interest in tumors and matched them with the normal tissues of 77 African-American prostate cancer patients. I did. They found that more than 35% of tumors in these patients had mutations that could potentially damage some of the other genes, including the DNA repair genes ATM, BRCA2, and ZMYM3. Did.

ZMYM3, which regulates chromatin and DNA repair, has been found to be one of the most frequently mutated genes in these patients. Of the 77 African-American patients, 9 (11.7%) had tumors with a mutation in ZMYM3, whereas tumors in 410 Caucasian patients whose data are included in the Genomic Data Commons database. Was 2.7%.

In addition, Xu et al. Investigated whether there were differences in copy count changes (when genetic material was acquired or lost) between African-American and Caucasian prostate tumors. The researchers pooled data representing 171 African-American patients and 860 Caucasian patients from several public databases.

They found a clear copy count change in more aggressive high-grade prostate tumors (Gleason score 7 and above) between African-American and white patients, but in low-grade tumors. I didn’t find it. High-grade tumors in African-American patients were more likely than tumors in white patients to have additional copies of the MYC oncogene and lack of the LRP1B, MAP3K7, BNIP3L, and RB1 genes. Acquisition of MYC and loss of MAP3K7 or RB1 were also associated with more advanced tumor stage.

Author’s comment:

Our findings show that clear genetic alterations in prostate cancer in African-American men may contribute to more aggressive prostate cancer and lead to higher mortality rates compared to white men. It suggests that. When confirmed in other studies, these results not only help understand racial disparities in prostate cancer, but also guide individual clinical management, such as prognosis prediction and targeted therapy guidance. I will. “

Jianfeng Xu, DrPH, Chief Author of Health Systems Research, North Shore University and Vice President of Translational Research

A future study by Xu and colleagues aims to understand how genetic alterations in African-American men affect recurrence, metastasis, treatment, and prostate cancer-specific death. In addition, they are interested in developing tests to detect such genetic alterations.

Research limits:

The limitations of this study are the small sample size, the use of various platforms to generate genetic data, and the execution of sequences between African-American male samples in this study and white male samples in the Genomic Data Commons database. Includes technical differences in method.