Distinct genetic alterations may factor into African American prostate cancer disparities

Prostate cancer disparities in African-American (AA) men may be caused, in part, by higher frequencies of certain genetic alterations leading to more aggressive disease, according to a study published in Molecular Cancer Research.^1,2

The researchers found that one of the most frequently mutated genes in the prostate tumors of AA patients was ZMYM3, a gene that regulates chromatin and DNA repair. The analysis found that 11.7% of AA tumors harbored these mutations, compared with 2.7% of tumors from white patients.

“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,” senior study author Jianfeng Xu, DrPH, vice president of translational research at NorthShore University HealthSystem, stated in a press release.

“If confirmed in other studies, these results will not only help to understand the racial disparity of prostate cancer but could also help guide personalized clinical management, such as predicting prognosis and guiding targeted therapy,” added Xu.

Pooling data from several public databases, the investigators sequenced 39 genes in tumors and matched normal tissue from 77 African American men with prostate cancer. The results showed that more than 35% of the tumors from AA men harbored damaging mutations in several genes, including APC, ATM, BRCA2, KDM6A, KMT2C, KMT2D, MED12, ZFHX3, and ZMYM3.

The researchers also investigated whether there was any variation in copy number alterations between the tumors from AA and white patients. Using data available for 171 AA patients and 860 white patients, the researchers identified distinct copy number alterations in the high-grade, more aggressive tumors (Gleason score ≥7). They did not, however, find distinct copy number alterations in low-grade tumors.

Compared to tumors from white patients, the high-grade tumors from African-American patients more frequently had deletions of the LRP1B, MAP3K7, BNIP3L, and RB1 genes and additional copies of the MYC oncogene. Loss of MAP3K7 or RB1 and gain of MYC was specifically linked to more advanced-stage disease.

“Prostate cancer incidence and mortality are highest in African American men, but the exact reasons for the disparity are not fully understood,” Xu stated in the press release. “The disparity is likely due to multiple factors, including socioeconomic differences and biology. We suspect that differences in the genetic changes that occur within tumors may play a critical role.”

Going forward, the researchers are now hoping to drill down further on their findings and learn specifically how distinct genetic alterations in the prostate tumors of AA men impact recurrence, metastasis, and mortality, and then translate this knowledge into precision treatments for these patients.

References

1. Genetic Alterations May Contribute to Greater Prostate Cancer Incidence and Mortality Among African American Men. Published online October 28, 2020. https://bit.ly/3e5e9rc. Accessed October 28, 2020.

2. Liu W, Zheng SL, Na R, et al. Distinct genomic alterations in prostate tumors derived from African American men. [published online October 28, 2020]. Mol Cancer Res. doi: 10.1158/1541-7786.MCR-20-0648