Random Mutations and Cancer in the news

Very recently in the news, there have been a lot of stories about how most cancers (2/3) are due to random mutation. This has been very widely broadcast and published and written about, and I debated whether to join the bandwagon. People tend to ascribe great significance to disease and/or illness. In the modern U.S.A., we seem to believe that we can somehow prevent everything bad from happening to us, to our health. The preponderance of dietary and lifestyle books are generally intended to help us with just that.

I will admit that my first thought on hearing about this story was “Oh thank god.” It has bothered me for a long time that the general public talks about finding “a cure for cancer.” It’s painfully evident that cancer is not just ONE THING. We have progressed from naming and treating cancers based on what organ or tissue they were found in to being able to identify what organ or tissue type they originated from (or are). Our therapies have advanced from chemotherapy and radiation therapy to specific monoclonal antibodies that target and destroy very specific cancer cells. Our understanding, detection, and treatment of various forms of cancer is much more nuanced today than it was even a decade ago.

But what causes cancer? Mostly, mutation. And biologically, there are only a two ways to get mutations: inherit them from your biological parents, or acquire them randomly throughout your life. Okay, so what can cause mutation? Well, radiation, smoking, and according to the media, pretty much everything in our lives is carcinogenic. Air? If it has secondhand smoke! Water? What about the pollutants and BPA? Nothing is safe!

Mutation is an inevitable consequence of LIVING. We know that mutations in our cells accummulate throughout our lives. Some mutations are good–otherwise we’d never have neat traits like Elizabeth’s Taylor’s infamous eye color. Some mutations are bad, like the ones that cause cancers. Some mutations don’t matter much. So who cares if you have a mutation in an important heart gene if that occurs in your toenail-producing cells? That gene wasn’t being used there anyway!

To put this in further perspective, if we look at a particular gene called APC, the functional part of this gene is 8,475 DNA bases long (2015). A loss of just one DNA base (#41 in particular) leads to a form of colorectal cancer known as Familial Adenomatous Polyposis (FAP)(Miyoshi et al., 1992). Although this particular form of cancer is inherited, there are 8,474 other potential places along this gene where a different mutation can cause the exact same form of cancer. That’s a lot of potential “causes” for just this one particular cancer. What caused that initial mutation? That is hard to say–and that is what we attribute to “bad luck.”

You have a trillion cells in your body. That’s 1,000,000,000,000. That’s a lot of cells. Most of them divide every now and then. Your skin, for example, renews much faster than your brain cells (which can actually divide). Your bones grow at a different rate. Some cells never truly get replaced (that’s usually scar tissue). The longer we live, the more these cells have to renew and replace (thus causing those stem cell divisions mentioned in most of the write-ups). Every time they do, more mutations arise just due to mistakes, kind of like genetic typos (have you spotted the one in this post?). The DNA copying is pretty accurate, but it still makes about 120,000 mistakes per cell. Fortunately, your cells also have some proofreading mechanisms that clean up those “typos”, reducing that ultimately to about one permanent mutation per cell each time it divides. (Pray, 2008) Most of the time those mutations are pretty harmless (do you need that lung gene in your eyelashes? Didn’t think so). However, the more often your cells have to divide, the better the chances that one of them will hit the jackpot and get a really (not-awesome) cancer mutation. Even then, don’t panic: the immune system actually probably cleans up most of those before they ever become problematic.

The point of this article (most excellently summarized in the Medline link below(Day, 2015)) is that for about 2/3 of cancers diagnosed today, there is no family history of disease, and no obvious contributing lifestyle factors such as high-risk carcinogens or behaviors, or standing in a gamma ray chamber hoping to become the Hulk, or painting with radioactive materials. These cancers therefore are assumed to be NEW mutations.

Even here, our advancing technology is allowing us to do what we’ve never been able to do before: sequence our genetics to look for genetic risk factors such as the BRCA genes known to cause breast cancer and other similar specific mutations (screening for FAP is available as well). These tests are usually reserved for people with family histories of disease, but the gene might even run in our families but we never knew it because disease was never diagnosed. What this research really highlights is that most of us don’t HAVE a history of disease. We are patient zero.

 References

Day, Mary E. (2015). Random Mutations Responsible for About Two-Thirds of Cancer Risk: Study, HealthDay News. Retrieved from http://www.nlm.nih.gov/medlineplus/news/fullstory_150227.html

Gene, NCBI. (2015). APC adenomatous polyposis coli [ Homo sapiens (human) ] Available from NIH NCBI Gene Retrieved 03 January 2015 http://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=324#reference-sequences

Miyoshi, Y., Nagase, H., Ando, H., Horii, A., Ichii, S., Nakatsuru, S., . . . Nakamura, Y. (1992). Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet, 1(4), 229-233.

Pray, Leslie A. (2008). DNA Replication and Causes of Mutation. Nature Education, 1(1), 214.

Protein, NCBI. (2014). adenomatous polyposis coli protein isoform a [Homo sapiens]. Available from NIH NCBI Protein Retrieved 03 January 2015 http://www.ncbi.nlm.nih.gov/protein/NP_001120983.2

 

 

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