Thursday, January 8, 2015

Cancer, the Cell Cycle and Bad Luck



The replication of cells has long been known to be responsible for tissue, organ, and species growth and reproduction. This, of course, is a highly regulated and controlled process that results in numerous differentiated cells performing a variety of specific tasks. Cancer on the other hand is uncontrolled growth of cells, where cellular differentiation is often lost. 

Proliferating cells (normal and cancerous) repeatedly transition between cellular duplication (interphase) and cell division (mitosis). This repetitive process has been described as a cycle. The concept of cell cycle was first utilized to describe these repetitive elements. The terminology (G0, G1, S, G2, and M) attempts to place in temporal perspective two dichotomies; mitosis (M), which can be determined by direct observation, and DNA synthesis (S), which can be established by DNA labeling. G1, the post mitotic gap, G2 the post-synthetic phase or pre-mitotic gap; and G0, a phase in which non-dividing cells exist, are terms used for simplicity (Figure 1).


cell Cycle
Figure 1. Schematic of the Cell Cycle
As I've been interested in the cell cycle most of my research career, I was quite intrigued by the January 2nd article in the journal Science that provides statistical modeling that links the number of stem cell divisions with cancer risk. The premise is that because cellular DNA replication causes errors (it's hard to replicate 3 billion base pairs correctly) the more laps around the cell cycle (i.e. DNA replication), the more likely that errors (mutations) will occur that could result in cancer. Thus tissues that require more cell divisions will be more likely to become cancerous than tissues that require fewer.  For this reason, cancers of the colon are more common than bone cancer. The article also states that heredity and environment play a significant role as well.  For example individuals with the Familial Adenomatous Polyposis (AFP) gene are at greater risk of developing colorectal cancer than those who do not carry this marker. Likewise smokers are of greater risk of lung cancer than non smokers (Figure 2).  Because of the topic there has been a great deal of commentary in the press regarding the paper.


plot of lifetime
Figure 2. Plot of Lifetime Cancer risk vs. Total Stem Cell Divisions of Various Organs [1].
Not surprisingly the lay press has taken this paper and run with it; the most common statement being that two-thirds of cancers can be attributed to "bad luck". While it is definitely not that simple (especially the math), there is some truth regarding  "bad luck".  But luck is only one part of the equation; our genetics, environment and personal habits also play substantial role, which the research paper so nicely states. While scientists have long believed that tissues with rapidly proliferating cells would be more prone to cancer, the data did not always fit this hypothesis. However, when STEM cell divisions were used for analysis a high degree of correlation was observed. Only recently has there been enough data regarding stem cell divisions to make these types of analyses, so I’m sure that this is just the beginning of a new avenue of statistical analysis of cancer. 

Cancer has touched all of us in some way. Very few have not had a family member or friend be diagnosed with or die of cancer. While these data suggest that many cancers are not preventable, they reinforce the need for better early diagnosis and effective treatments for cancers. Most of those afflicted want to know why they have cancer and if they could have avoided it somehow. While the 3-pack a day smoker who gets lung cancer has a pretty good idea as to why they were afflicted, for many others the answer really is bad luck.

References:
  1. Tomasetti, C. and B. Vogelstein (2014) Variation in Cancer Risk among Tissues can be explained by the Number of Stem Cell Divisions, Science, 347:78-81.


By: BioTek Instruments, Paul Held Ph.D., Laboratory Manager

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