Your genes just aren’t enough to define your risk

Writing in the July issue of Genomic Medicine, Fredrik Wiklund (an expert on the genetics of prostate cancer) states that, “[R]ecent genome-wide association studies have revealed numerous genetic variants” associated with prostate cancer. He continues by stating,

The risk variants identified using case-control designs that compared unaffected individuals with all types of patients with prostate cancer show little or no ability to discriminate between indolent and fatal forms of this disease.

Over the past 10 years or so, our knowledge of the genetics of prostate cancer has expanded significantly. There are now believed to be at least 24 different genetic subtypes of prostate cancer, based on the research conducted by people like Dr. Wiklund. However, we have yet to be able to categorically link the presence of any one genetic subtype or set of genetic subtypes to risk for either indolent or aggressive forms of the disease in prospective clinical studies.

Dr. Wiklund goes on to note the possibility that, “different genetic components are involved in the initiation as compared with the prognosis of prostate cancer.”

What Dr. Wiklund is proposing makes perfect sense for a form of cancer that can take 20 or more years to develop into an indolent or an aggressive disease. Effectively he is saying the following:

  • Initial risk for prostate cancer is likely to be based on the presence or absence of specific genetic subtypes or SNPs (genetic predisposition). But …
  • The clinical expression of prostate cancer may also be based on other biological factors that allow the initial growth of prostate cancer cells. And …
  • The appearance of more aggressive forms of prostate cancer may also depend on secondary biological factors that allow for accelerated growth of certain types of prostate cancer cell.

Let’s see if we can give an an analogy.

  • Susie is the 12-year-old daughter of two former swimming world record holders and Olympic champions.
  • She clearly has the the right genes and the right physiology to make her a great swimmer, and when she is in the mood she can beat anyone in her age range (most of the boys included).
  • But Susie has no real interest in swimming. She doesn’t have the need to “win” in the same competitive manner that her parents did. And she hates training because it takes away her time to study biology, which she loves.
  • Susie is still “driven” (she got those genes from her parents too) — but not at swimming. In 2027 Susie and her colleagues will publish a paper that revolutionizes the diagnosis and early management of prostate and breast cancer when they discover a completely new and unexpected biological mechanism responsible for “turning on” and “turning off” the growth of hormone-sensitive cancer cells in 95 percent of humans.

It is all too easy to want to believe that prostate cancer (and other forms of cancer) might be like one of the truly heritable diseases that are utterly dependent on one’s genetics, such as sickle cell anemia or Huntington’s disease. Unfortunately, it just isn’t going to be that simple. The development of prostate cancer in any specific individual is most probably a multi-stage process. It may well be linked to the genes you are born with, but it is also quite certainly linked to other things that happen as you age. As yet, we have minimal understanding of what those “other things” really are.

4 Responses

  1. Thanks Sitemaster for featuring this important and lively issue.

    Those in our survivor community with several generations who have developed prostate cancer have cause to be grateful that prostate cancer genes are not destiny for our children, or for ourselves, regarding lethality, but it can help our cause to be aware of the added genetic risks.

    The American Association for Cancer Research has devoted a lot of attention to genes and their expression at its annual meetings. One fairly recent meeting focused heavily on the “epigenetics” of cancer, meaning the biological environment outside the cell that affects the development and progress of cancer. As a survivor representing prostate cancer as part of the AACR’s Scientist↔Survivor Program, I heard the catchy analogy that cancer genes are like light switches, some bigger and more easily flipped (more intrusive) than others, but the environment outside the cell is what turns the switches on and off. It’s better not to have the bad switches and to have the good ones, but at least there are things we can do to try to flip the switches to the best position, though our level of current knowledge and confidence is limited.

    I’m convinced that diet, nutrition including supplements, aerobic and strength exercise, and stress reduction all matter. As just one example, the early research now being done in Boston on selenium, by Dr. Kantoff and colleagues, in a series of studies is intriguing, helping illuminate the puzzling trial and clinical results with this important element. They are finding that variations on genes like SEP15 and SOD2 appear to make a difference in whether selenium is helpful, neutral, or even, perhaps, harmful, to prostate cancer survival prospects. (Personally, I’m sticking with yeast-based selenium as I have done unusually well with my challenging case at the 10.5-year point. I realize that it may not work for everyone, but I have a hunch it is working for me. I hope some day I’ll be able to put that to a test based on solid knowledge of the underlying biology.)

  2. … and yet there are many situations like my own out there where on my father’s side of the family my grandfather, my father, two of his brothers, and I all have had prostate cancer, and on my mother’s side of the family there are no known cases, and my mother and father grew up in the same small town drinking the same water, eating the same sorts of foods, etc.

    Three generations of my father’s side of the family have recently submitted blood samples to the generations/genetics study being conducted at the University of Michigan in hopes of helping to sort this confusing issue out some day.

  3. John:

    It is precisely families like yours that may help us to begin to understand ‘what those “other things” really are.’ Thank you for participating in the University of Michigan studies.

  4. I have been in a similar study since about 2000. It’s run under the auspices of the Mid Atlantic Cancer Genetics Network, and my particular arm of the work is being managed by Johns Hopkins, with Dr. Patrick Walsh as the official head of the project. It involved submission of a blood sample plus detailed data on me, my case, and my family, and I get annual update questionairres. Apparently this particular study is nearing conclusion.

    I hope many of us will get involved in this kind of research. It involves little of our time and effort, yet the payoff could be huge.

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