Are Prostate Tumor Germline Mutations Linked to Genetic Ancestry?

By: Kayci Reyer
Posted: Thursday, December 15, 2022

According to research presented in Cancer Research Communications, genetic ancestry may affect prostate tumor biology such as DNA damage repair pathways. Specifically, some mutations in DNA damage response found in prostate cancer samples from Nigerian men may be correlated with African ancestry. These research findings were presented in Cancer Research Communications.

“We identified unique variants in the BRCA1 gene that are not typically tested for in the clinic, and these variants were specific to African ancestry,” noted Clayton Yates, PhD, of Tuskegee University, Alabama, in a press release from the American Association for Cancer Research. “On the other hand, tumors from European Americans had variants in different DNA repair genes that were not observed in tumors from African American or Nigerian patients. This suggests that different variants contribute to prostate cancer in European Americans compared with men with African ancestry.”

The study included prostate tumor samples from 45 Nigerian men with advanced-stage, treatment-naive disease plus 11 unmatched nontumor samples from African American and European American men with prostate cancer. Samples underwent whole-exome sequencing.

A total of 111 germline variants were identified. Among them, similarities in germline alteration patterns in the African American and Nigerian cohorts were noted, including BRCA1 (100%), BARD1 (45%), BRCA2 (27%), and PMS2 (18%). BRCA1 was found to have a statistically greater frequency of mutation in patients of African ancestry; a positive correlation between African ancestry and variant frequency was observed. Only men of African ancestry were found to harbor BRCA2_rs11571831, whereas the frequency of BRCA2_rs766173 was elevated in Nigerian patients.

Overall, 26 genes associated with prostate cancer in the Nigerian cohort contained 133 somatic variants, with mutation frequencies 10% or higher in BRCA2, APC, ATM, BRCA1, DNAJC6, EGFR, MAD1L1, MLH1, and PMS2. In a comparison of African American and European American samples, Nigerian tumors had statistically higher occurrence rates of BRCA1, BRCA2, and APC.