Posted April 21, 2015
Bernard Kwabi-Addo, Ph.D., Howard University
The incidence and mortality for prostate cancer is about twofold higher in African American (AA) than Caucasian (CA) men, with AA men experiencing among the highest rates worldwide. African-American men with prostate cancer are disproportionately at risk of being diagnosed with the disease at an early age and also at an advanced stage of the disease. This disparity is thought to be the result of a combination of gene-environment interactions, behavioral factors, socioeconomic factors, and genetic factors. In addition to genetic defects (i.e., gene mutations, translocations, etc.), we know that aberrant DNA methylation plays an important role in prostate cancer by switching off genes that suppress cell proliferation, apoptosis, and metastasis. Dr. Bernard Kwabi-Addo, previously identified differential methylation changes of several key regulatory genes in prostate tissues from AA versus CA men, now with funding from a FY10 PCRP Health Disparity Research Award, he is performing the first genome-wide study to investigate the association between DNA methylation and prostate cancer disparity in normal and prostate cancer tissue samples from AA and CA men.
Overall, Dr. Kwabi-Addo observed higher frequencies of methylated genes in AA prostate cancer than in CA prostate cancer samples. Although he found that there were 330 methylated genes shared between AA and CA prostate cancer tissues, he also discovered that when AA and CA tumor samples are compared, there are almost 3,000 genes that are uniquely methylated in the AA samples. Cancer cells displayed higher methylation and low levels of gene expression, whereas normal prostate cells had lower methylation and higher gene expression levels, suggesting that methylation leads to some loss of gene expression. Since the cancer samples from CA men had slightly higher Gleason score and similar pathologic staging, when compared with the AA samples, the higher prevalence of methylation seen in AA cancer samples is not simply reflective of differences in disease aggressiveness or stage between the two groups, but may reflect differences in genetic susceptibility to methylation, lifestyle, or other environmental exposures such as diet.
These observations suggest that differential gene expression induced by DNA methylation could contribute to the aggressive prostate cancer observed in AA patients and may have important implications for understanding prostate cancer health disparity as well as precision treatment of prostate cancer in different ethnic groups.
Venn diagram showing the number of differentially methylated genes probe sets of Cancer (Ca) versus normal (NI) for African American (AA) and Caucasian American (Cau) groups and the number of overlapping probe sets between the 2 groups.
Devaney JM, Wang S, Furbert-Harris P, Apprey V, Ittmann M, Olender J, Lee NH, Kwabi-Addo B. 2015. Genome-wide differentially methylated genes in prostate cancer tissues from African-American and Caucasian men. Epigenetics (In Press).
Devaney JM, Wang S, Funda S, Long J, Taghipour DJ, Tbaishat R, Furbert-Harris P, Ittmann M, and Kwabi-Addo B. 2013. Identification of novel DNA-methylated genes that correlate with human prostate cancer and high-grade prostatic intraepithelial neoplasia. Prostate Cancer and Prostatic Diseases 16(4):292-300.