We all begin life as a single cell - a zygote - the result of fertilization of one of our mother's eggs by a sperm from our father. In time, and after many cell divisions, a multitude of different cell types form, each destined to carry out a specific function, each with distinct physical and biochemical properties. This process, whereby a cell becomes committed to a specific identity is called differentiation. The mechanism of differentiation has been worked out: A cell becomes differentiated by transcribing a limited portion of its genetic endowment. Each of the two hundred or so different cell types employs a specific and limited set of genes.
Normally, differentiation is irreversible. Liver cells don't become muscle cells, and nerve cells don't become skin cells. So it was surprising to the scientific community that cells don't lose genetic information during differentiation, despite the fact that much of their genomes goes unused. It's now firmly established that every cell, regardless of its differentiated state carries the same complement of DNA as a zygote. It certainly appears to be an inefficient design strategy since every time a cell replicates its DNA it uses a considerable amount of energy to insert the correct base in the right order into the newly forming strands. If a cell eliminated all the DNA that it didn't need during differentiation, it would save a lot of wasted energy.
But carrying a zygote's worth of DNA in every differentiated cell has another, more serious, drawback. It opens up the possibility that a rogue cell could make use of genes that it normally has no access to and thereby behave inappropriately. One such abnormal behavior is called cancer. Cancer begins with a single cell. Somehow one of its genes has mutated (acquired a change in DNA sequence). Suddenly, instead of behaving as a neighborly member of a multicellular society it begins to act selfishly, proliferating abnormally. New mutations occur as the cells divide. Then evolution via natural selection takes over. Offspring of the original mutated cell that are best able to survive and reproduce are favored over those cells that are less capable. Soon a tumor forms. It it not removed, it may continue to grow. Additional mutations may occur that allow the cells to escape the original mass of tumor cells and travel through the lymph system or blood vessels to other sites, a process called metastasis. Without medical intervention, the outcome may be dire.
Types of Cancer
More than 80% of cancers arise in epithelia - tissues that "line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs." (Wikipedia). Cancers that originate in epithelial tissues are called carcinomas, and their prevalence in this type of tissue probably reflects the fact that epithelial cells divide rapidly. Breast, prostate, lung, colon, liver, stomach, and pancreatic cancers are carcinomas. Only about 1% of cancers arise from connective tissues (sarcomas) and a little less than 10% from blood forming tissues (leukemia, lymphoma, multiple myeloma). In addition, there are cancers of nervous tissue, pigmented cells of the skin (melanoma), and even eggs and sperm. Practically any cell capable of cell division can switch from a normal member of the cellular community to one that pursues its own selfish interests and proliferates uncontrollably.
Carcinomas, sarcomas, and the other members of the cancer panoply are caused by errors in genes - mistakes in the sequence of DNA. But what causes these errors, these mutations? I think that many people when asked this question would answer that most mutations are caused by harmful agents that originate from industrial processes. Air pollution, atomic reactors, artificial chemicals added to our foods, pesticides, and the like would be examples that many would cite. After all, they would say, haven't cancer rates been rising in the modern era?
Cancer is now more prevalent than it was in previous centuries, but that's because we're living longer and cancer is a disease primarily of the old. The fact is that there is strong evidence that the factors listed above are not the primary drivers of carcinogenesis, One surprising case in favor of this view is cited in chapter 20 of "Molecular Biology of the Cell". They argue that in the absence of agents that cause mutations (mutagens) an error in DNA sequence occurs on the average once per cellular division. You can calculate that this means that that on average any given gene will experience a change in sequence once every million cell generations. Alberts et al estimate that in a lifetime a normal human will experience 10 quadrillion divisions (that's a one with 15 zeroes). Dividing the number of divisions by the rate of mutation results in the amazing estimate that every gene in our body will be subject to a change in sequence ten billion times! All this without any external mutagens. If all it took was a single mutation in a growth promoting gene, cancer would be be much more common. The reason it isn't is that more than one event must occur independently in the same cell. That's one reason that cancer rates increase with age.
Of course I'm not saying that external agents aren't ever responsible for cancer. On the contrary. The chemicals in cigarette smoke and the ultraviolet radiation from the sun are major contributors to lung and skin cancer. Asbestos and X-rays are proven carcinogens. There are viruses that have been implicated in cancer. And even some common components of our diet, like burnt toast and grilled meats, are known mutagens and are suspected carcinogens. In addition, as I'll discuss later, genes that are defective in repairing DNA errors can increase the rate of cancers significantly.
In summary, cancer is a disease cause by mutations in genes. While cancer may begin with a single mutation, it takes several errors in multiple genes for the disease to progress to where it is harmful. Which genes? Next time.