Cancer is one of the first world's leading health problems. As such, it is the focus of a large amount of research and much more is being discovered about it each day. What has been known for a while now is that cancer occurs when a cell loses control due to a loss of regulation and begins multiplying too frequently. This abnormal new cell growth, neoplasia, may result in a tumor, a growth of new tissue. This tumor may be benign (stationary) or malignant (capable of invading surrounding cells and/or metastasizing and spreading), and may be a solid or a suspension. Regardless, it is a potential health risk, and one encountered by an increasing number of people each year. What has not been known for as long a period of time is how cancers form. Only recently has it been discovered that cancer is a genetic disease. From this discovery, a genetic theory of cancer has been developed. This theory holds that "sequential accumulation of somatic mutations lead to inappropriate proliferation," (Dr. G. Thomas, Penn State Biology department). It follows, then, that hereditary cancers can occur when the first mutation is already present in the germ line.

One important collorary of the genetic theory of cancer arises rapidly from its definition. If mutations are acquired sequentially, it should be expected that the smallest (and hence earliest) tumor should contain cells with one specific mutation. As the tumor grows (and progresses through time), it should later contain onlyu cells with two specific mutations. And then three, then four, and so on. This is important in the treatment of cancers. It means that if person one has a cancer that has metastasized, all of the cancers in his/her body should be treatable with the same medicine because they all have the same mutations. But person two may have the same cancer arising from a different set of mutations, so person one's medication may not be effective on person two. These conditions have been found to be true in a majority of the cases (although there are exceptions where, in the later stages of cancer development different mutations arise in different parts of the cancer).

Epidemiological estimates suggest that most final forms of cancer contatin three to seven new mutations. This is a number higher than expected, and can only be explained by increased mutation rates in cancerous cells. Increased mutation rates can best be explained in one of two ways: either through exposure to mutagens (and hence usually carcinogens), or through a mutation in a DNA repair mechanism. Both of these possibilities are found in human patients. An example of a mutagen affecting cancer rates can be found by looking at benz(a) pyrene, found in cigarette smoke and possibly causing lung cancer. An example of a mutation in a DNA repair mechanism involves the gene p53. P53 is a tumor suppressor gene that codes for a protein that halts the cell cycle when DNA has not been correctly synthesized. Approximately 50% of all cancers contain mutations in p53, meaning that the three to seven mutations arise because DNA is replicated before it is correctly repaired.

Tumor suppressor genes are genes involved in the growth inhibition pathways. In a pathway such as this, mutations that inactivate a protein prevent the protein from inhibiting the growth of a cell, possibly resulting in cancer. This type of cancer is often found in families and is passed down through generations. An example is Li-Fraumeni Syndrome, which involves a heritable mutation in p53.

This is not the only way to get cancer, however. ANother category of mutation that can lead to inappropriate proliferation involves oncogenes and usually affect the growth factor pathway. A general theory of cell growth maintains that a growth factor will interact with a receptor which will start a signal cascade eventually leading up to gene expression. This gene expression then leads to new growth. Usually this new growth is strictly regulated through the growth inhibition pathway discussed above and through contact inhibition. Contact inhibition prevents cell growth deleterious to surrounding cells by providing feedback to the growth factor pathway. However, mistakes are possible. If a dominant mutation were to occur in this pathway, it could potentially remove all cell growth regulation. A dominant mutation in this mpathway may be one such that the receptor or the signal, or any one of a number of possibilities moving down the pathway, is altered such that the signal remains "on" even when it should not. This provides the cell with continuous instructions to grow, which removes the contact inhibition normally observed in non-cancerous cells. Genes in which this scenario can occur are called protooncogenes (if in normal form) or oncogenes (if already mutated).

This type of mutation can be caused by viruses through two major methods. First, a virus could contain the oncogene itself. This gene would then be expressed by the host cell if the virus inserts itself into a host chromosome. Secondly, a virus could contain a very strong promoter. If the virus does, and it integrates itself into the host DNA at a point just upstream of a gene in the growth factor pathway, that gene may be over-expressed, leading to a lack of contact inhibition. In this second case then, the protooncogene is already in the cell, but is only made an oncogene through interaction with a virus.

Although much is still unknown about cancer, it is very evident that a wealth of information is available for study. And all of it points to cancer being a genetic disease.

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