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DNA mutations alter a cell's behavior
A cell is like a miniature factory in which each worker (protein) is responsible for carrying out a specific task for the good of the unit. Every protein has its role. When a protein’s structure is changed by gene mutation, then the function of that protein is also changed. Some mutations cause a protein’s capabilities to be enhanced, like a weight lifter on steroids, whereas others cause its role to be lost entirely.
A critical breakthrough in our understanding of cancer was the discovery by Dr. J. Michael Bishop and Dr. Harold E. Varmus that mutations in the genes that control the normal growth patterns of a cell can transform these good genes into bad genes, which they termed oncogenes. The study of oncogenes exploded after their findings, which were rewarded with the Nobel Prize. In contrast to normal genes, oncogenes spawn proteins that are supercharged at promoting growth, spread, and survival, cancer’s three essential properties. These overactive molecules are being targeted and quieted by new cancer-fighting drugs.
On the other hand, mutations to genes that serve as brakes on cancer growth and survival, called tumor suppressor genes, result in the loss of these important safeguards. Gatekeeper and caretaker genes are also types of tumor suppressor genes: by repairing mutations, they prevent cancer from developing. It is much harder to replace a lost tumor suppressor gene than it is to block an overactive oncogene. Replacement requires insertion of the lost gene into cells through a technique called gene therapy, whereas blocking is accomplished with drugs. To insert a gene into every cancer cell is a daunting technical task. As of this writing, there are no approved gene therapies for fighting cancer.
The combination of generating oncogenes and crippling tumor suppressor genes leads to a toxic imbalance in the cell that tips the balance in favor of uncontrolled growth. The result of all these mutations is a full-blown cancer cell. It is thought that a minimum of four mutations are needed to generate cancer, although most cancers contain far more. For common cancers, such as prostate, breast, colon, and lung cancers, it takes many years for enough mutations to accumulate to give rise to cancer. This process is speeded up if an individual is born with a critical gene mutation.
The dependence of our DNA on the gatekeeper and caretaker security systems to prevent mutations is made crystal clear by what happens when these systems malfunction. Their breakdown is found in nearly all cancers and is believed to be one of the earliest changes in the process of converting a normal cell into a cancerous one. We have learned a great deal about these systems from families who have a hereditary predisposition to cancer. Inherited mutations in gatekeeper or caretaker genes are common in such families.
Family Cancers
Because cancer is so prevalent, many individuals have some family history of it. These histories can vary quite a bit. One person may have only an uncle with prostate cancer, whereas another may have a brother with bone cancer, a sister with breast cancer, and a father with lymphoma. How do you know if your family medical history indicates that your family is especially prone to cancer? And to which cancers in particular? A properly taken family cancer history, genetic counseling, and appropriate genetic testing can help determine if there is a strong, moderate, or low family and individual risk of cancer.
In trying to understand one’s risk of developing cancer it is important to note that most cancers affect us in a pattern that is called sporadic: they occur in individuals without an apparent family concentration of the same type of cancer. The reasons for sporadic cancer development have more to do with environmental influences and aging (cancer is more common in those over age sixty) than to an inherited, genetic predisposition to cancer. This is not to say that one’s family DNA is unimportant, because it is. What it does mean is that a single inherited abnormal gene is not the cause of most lung, colon, breast, pancreas, prostate, melanoma, lymphoma, or other common cancers.
Yet for approximately 5 to 10 percent of all those with cancer, one mutant gene, passed down in the family DNA, is the primary cause. The specific DNA mutation typically causes the corresponding protein to lose function. For example, mutations in the genes that lead to inherited forms of breast and ovarian cancer, BRCA1 and BRCA2 (BReast CAncer), prevent the full proteins from being generated; this renders them unable to perform their functions in the cell (it’s like cutting off a boxer’s arms). Because BRCA1 and BRCA2 function to direct the repair of damaged DNA, loss of BRCA1 or 2 activity permits a cell’s DNA to accumulate the damage that can result in cancer.
Inherited genetic mutations are more widely known to cause such medical disorders as hemophilia, sickle cell anemia, Tay-Sachs disease, and muscular dystrophy. But the same principle holds for all inherited genetic diseases: a gene with an important role in the body exists in a mutant form in the affected individuals, leading to a particular health problem. In the case of muscular dystrophy, mutation of a muscle gene called dystrophin causes severe debility. In the case of family cancers, mutations are often in genes that prevent a cell from maintaining its DNA, resulting in mutations to additional genes. These family cancer genes are called cancer susceptibility genes.