By Mike Cusnir MD
I’ll take advantage of this blog and show my kids that despite a career in medicine, math still has a role. If we start looking at the numbers, humans have 23 pairs of chromosomes and here is where the “bad luck” starts. These chromosomes are composed of 20,000 genes and these genes have 6,469.000.000 pairs of nucleosides or “letters” in the genetic code; when the cells are dividing for any reason (growing, healing, etc.) these “letters” need to be replicated, but a single mistake could activate a gene and several of this mistakes could create a cancer. If we keep crunching the numbers there are 37.2 trillion cells in the human body (that is 37,200,000,000,000), and an average person has a body surface area of 1.6 m2. If we do a simple rule of 3 (you see kids, math is useful) in an area as small as 0.001 m2 or 0.3 inches – equivalent to the tip of your tongue – every time you bite yourself or burn yourself with pizza, this area needs to be healed with 232,500.000.000 new cells and 6,469.000.000 bases in each cell (sorry I can’t post the actual number because my calculator shows an error). But even if the calculator shows an error it would be expected that in this massive photocopy of cells there would be cumulative mistakes.
These numbers are far more incredible if we think about how we come to this world. After conception, 1 cell divides to create a human being that grows to an adult size with 37.2 trillion cells, so just for kicks, calculate how many divisions it takes for one cell to become 37.2 trillion. Now think how many mistakes can occur during those “photocopies”.
This is the background for the controversy in cancer this week created by an article in the Journal Science. Science articles don’t tend to stir up much controversy since they are from very reputable sources and are written by leaders in their respective fields. The article in question is not the exception except on the discussions that it has caused.
In 1980, Dr. Bert Vogelstein proposed the original theory that cancer occurs when there is an accumulation of sequences of mutations resulting in a change of the nature of the tissue from a mature tissue to one that behaves in a more primitive fashion, replicating more often and not respecting its boundaries, and ultimately spreading to other organs were that tissue has no business.
In his present research, Dr. Vogelstein presents evidence that most cancers are caused by these mistakes in replication of the genetic material as the cells divide for normal reasons, in summary by bad luck. The other two causes of cancer that have been investigated are hereditary causes and environmental or bad behavior of the person.
On one hand, as cancer doctors we love the idea of being able to tell the patient nothing that he/she did caused the cancer and for parents of a cancer patient to have the reassurance that they did not transmit the cancer code (genes) to their kids. However, the main topic for discussion is that we are doomed to have cancer and there is nothing we can do about it. Moreover, can we behave badly and not be concerned with the consequences such as smoking, obesity, alcohol, etc.
What I intend to comment today is that those replicative errors can be the result of risky behaviors, since most of these errors will be more frequent if we make the cells divide more by creating inflammatory conditions as a result of those risky behaviors or environmental factors that still account for up to 20 to 30 % of all cancers but on cancers that are of higher incidence, so if we crunch the numbers again (enough of this, I’ll just take them from the article) 42% of the cancers could be prevented by what we do (or don’t do) every day. And worse than this, but I don’t want to open another can of worms, is that recently on colon cancer, the most prevalent mutation pathway is on a gene called WNT that starts to be expressed on the 4th day after conception which almost completely undermines the theory proposed by Vogelstein in 1980 not to mention his current article.
To close, only two takeaway messages: math has a role in medicine and our behavior continue to have a role in cancer development despite evidence of the involvement of bad luck. Why add mistakes of our own, creating more errors and supporting the theory that what causes the cancer is the accumulation of several slipups in our DNA and not a single matter. So, kids keep studying math and keep the preventive behavior in cancer despite knowing that some days are just not our good luck days.