Saturday, June 7, 2014

We Are All Mutant

Mel Greaves' article "Does everyone develop covert cancer?" discusses that while around 1 in 3 individuals will develop overt cancer, there is increasing evidence that most, if not all, people in their lifetimes develop covert cancer. Greaves begins by defining covert cancer as cancer that is "hidden and subclinical" but that can be "uncovered by more incisive interrogation," as opposed to overt cancer, or full-blown, malignant growths or tumors. The evidence for these covert cancers is primarily gathered from autopsies of individuals who died for non-cancerous reasons. Most autopsy reports show a substantially higher frequency of pre-malignant lesions, or carcinoma in situ (CIS), than of clinical cancer frequencies or cumulative life-time risk of developing overt cancer. This suggests a much higher frequency of CIS than is commonly believed or recorded.

Figure 1. Average incidence of cancer by age.
We discussed this graph in class numerous times. It is widely accepted that the risk of overt cancer increases with age; this figure clearly depicts that. However, it can be asserted that the risk of covert cancer increases with age as well. As many as 1 in 5 newborns have covert, pre-malignant cancer. If the rates of CIS are this high in individuals at birth, then it is not much of a stretch to think that most people develop CIS in their lifetime.

Upon looking at mutation rates of DNA, the high frequency of CIS is unsurprising. DNA is extremely vulnerable to error-prone replication and damage, and it often "lacks perfect fidelity of repair" (Greaves). Couple that with the immense number of cells replicated per day, and the numbers are in favor of CIS. Our bone marrow and intestinal epithelia produce 1011 cells per day, and mutation rates average around 108–109 per base pair per cell cycle (Greaves), so it is inevitable that mutations arise. 

In addition to these natural functions, our bodies are constantly surrounded by environmental factors that are "mismatched with our genetic heritage" (Greaves). Exposure to carcinogenic tar from tobacco, excessive UV rays, and persistent hormonal drive due to early pregnancy and prolonged breastfeeding are unnatural, and hugely increase DNA mutation rates .

With that, we can assume that mutations naturally arise all the time due to endogenous processes and exogenous influences. Longer lifespans caused by increased technology and medical care provide more time for these mutations to occur. 

An issue with this high prevalence of CIS is how to differentiate the ones that have a higher propensity for developing into malignant cancers that merit higher degrees of intervention. A measure that is currently being used is limiting the progressive ability of the CIS, with the help of non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs have been found to reduce the risk of overt cancer very effectively. It is ironic that the most effective way to prevent overt cancer from forming is with the use of the most common household drug, aspirin. 

I found this article to be very thought-provoking. Everyday you hear of another thing that purportedly increases our risk of cancer. With so many negative environmental factors that we come in contact with everyday, it is not surprising that CIS is so common. It is something that everyone should be aware of, although it is not something that everyone should fear. I think this article was a little dramatic in this way. Yes, CIS is very common, but oftentimes there is very little associated risk. I would have appreciated more data on the numbers of CIS that develop into overt cancer; I would assume these numbers to be relatively low. Overall, though, I think this article raised good points and presented logical data for the topic.

Greaves, Mel. "Does Everyone Develop Covert Cancer?" Nature Publishing Group, 13        Mar. 2014. Web.