CNV analysis hints at hereditary susceptibilities for prostate cancer


An new article on line in the Proceedings of the National Academy of Sciences or PNAS has further extended our understanding of the genetic and inheritable factors that may predispose individual patients to higher risk for clinically significant and aggressive forms of prostate cancer (although how to apply this information to the diagnosis and work-up of specific patients is going to take some time to work out).

Demichelis et al. used a technique known as “copy number variant” (CNV) analysis to identify functionally active areas of individual patients’ genomes that were associated with susceptibility to prostate cancer.

Specifically, the authors looked at the genetic makeup of nearly 2,000 Caucasian participants in the Tyrol Prostate Specific Antigen Screening Cohort and were able to identify two CNVs that seem to be strongly associated with risk for prostate cancer. (Now please remember that a “strong association” is not the same as a cause and effect relationship. All that this study can tell us is that specific genetic variants are commonly found in in men diagnosed with prostate cancer and are not found in men not diagnosed with prostate cancer.)

Here are the core data from the study:

  • The trial was based on blood samples from 867 men diagnosed with and 1,036 men without prostate cancer given PSA tests since 1993.
  • All trial participants were between 45 and 75 years of age.
  • The two genetic loci with highly functionally active CNVs are
    • 15q21.3 which overlaps with a non-coding enhancer element that contains multiple activator protein 1 (AP-1) transcription factor binding sites
    • The α-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase C (MGAT4C) gene on 12q21.31.
  • The MGAT4C gene appears to significantly modulate cell proliferation and migration in benign and in cancerous prostate cells, and to be significantly over-expressed in men with metastatic (as opposed to localized) prostate cancer.

In a second, confirmatory, study, the authors were able to replicate and confirm these two risk associations in a second, entirely separate cohort of 800 men who were also screened for prostate cancer using the PSA test, at least implying that this association between the presence of the two CNVs and risk for prostate cancer is “real” … and just not a finding that can be explained by random chance.

A separate report on this study is available on the HealthDay web site today, where the senior author of the study, Dr. Mark Rubin, is careful to point out that, “This is the first study to suggest these variants may account for susceptibility to [prostate] cancer. This new line of research will also allow us to study the biology around prostate cancer initiation.”

One Response

  1. With so much more money going for breast cancer research than prostate cancer with the morbidity and mortality of both being almost similar, it is time for heightened advocacy for more and better prostate cancer dollars and research.

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