14. Ethnic and molecular disparities in prostate adenocarcinoma incidence: Data from 19 cohort studies

Abstract

Prostate cancer is the most commonly occurring cancer in males overall, but ethnicity is a strong predictor of incidence. African and non-Hispanic Caucasian ethnicities possess the highest incidences, while those of Asian, East-Asian, and Indigenous peoples have the lowest. Comparisons between the genomic alterations of Asian, African, and non-Hispanic Caucasian (nHC) ethnicities have indicated that PTEN losses, and FXA1 alterations are common irrespective of ethnicity. While ERG deletions are less common in Asian populations, compared to African and nHC ethnicities. The ethnic contribution to prostate adenocarcinoma (PAC) was further evaluated using the cBioPortal Genomics data tool from Memorial Sloan Kettering (MSK). An evaluation of Asian (East Asian/Asian; N=131), African (N=165), and nHC (N=3,642) from 19 cohort studies, totaling 3,938 individuals, was undertaken. Overall survival outcomes were highest for nHC, individuals followed by African individuals. Comparative hazard ratios were highest for Asian individuals at 1.6. Expectedly, FOXA1, TP53, and SPOP were among the most commonly altered genes in each ethnicity. Copy number alterations (CNAs) in 74 genes, including amplification of the antigen receptor gene (AR), were significantly enriched in Asian PAC (p=4.6 × 10-3). CNAs in 14 driver genes were enriched in Asians and tended to be co-altered. Mutations in 66 genes were enriched in Asians, including in mutations in ATRX, CDK12, FH, NF1, and RAD51D that tended to co-mutate. Finally, 16 genes were found to be altered exclusively in a minority of the Asian population, including BLM, and CHD2. The described molecular differences may contribute to the ethnic disparities of PAC incidence.