Genetic risk, aggressive prostate cancer, and ethnic/racial differences

According to a newly published article in the Journal of Clinical Oncology, there are new and strong indications that a specific “genomic fingerprint” is associated with elevated risk for diagnosis of aggressive prostate cancer in African Americans compared to Caucasians.

The article just published by Yamoah et al., along with a media release issued by Thomas Jefferson University define a subtype of prostate cancer that the research team has defined as “triple negative prostate cancer.” They define such triple negative disease as prostate cancer exhibiting the absence or the expression of only low levels of three genes called ERG, ETS, and SPINK1.

Yamoah et al. started by identifying 20 genes that have been shown to be functionally associated with prostate cancer initiation and progression. They then examined clinical records of prostate cancer patients to find a pool of 154 African Americans and 243 European Americans whose prostate cancer characteristics were matched using the validated CAPRA-S scoring system, indicating that the patients had very similar disease at the outset. By analyzing tissues and other biological samples from these patients, the researchers were then able to determine which of the 20 validated genes — some of which initiate and some of which drive development of cancer — were expressed in high or low quantities in the two populations of men.

They found that:

  • 6/20 biomarkers showed statistically significant differential expression in African Americans as compared with European Americans men in one or more statistical models.
  • These six genes included
    • ERG (P < 0.001)
    • AMACR (P < 0.001)
    • SPINK1 (P = 0.001)
    • NKX3-1 (P = 0.03)
    • GOLM1 (P = 0.03), and
    • The androgen receptor gene (P = 0.04).
  • Dysregulation of AMACR (P = 0.036), ERG (P = 0.036), FOXP1 (P = 0.041), and GSTP1 (P = 0.049) and loss-of-function mutations for tumor suppressors NKX3-1 (P = 0.025) and RB1 (P = 0.037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner.
  • Dysregulation of GOLM1 (P = 0.037), SRD5A2 (P = 0.023), and MKi67 (P = 0.023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years.
  • 51 percent of men of African American ethnicity had triple-negative disease as compared to 35 percent of men of European American ethnicity (P = 0.002).

This study provides us with additional information about why African Americans appear to have an elevated risk for diagnosis with and death from prostate cancer as compared to European Americans. Clearly the presence of “triple negative” prostate cancer is not the only reason. Other factors are certainly involved in this risk. However, this type of expanded knowledge will, over time, lead to improvements in the early diagnosis and work-up of prostate cancer and provide a sound rationale for when more aggressive forms of early treatment are likely to be appropriate in carefully identified patients.

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