Introduction to Cancer

Cancer is a common disease. One out of every 3 people in the United States will develop some form of cancer in their lifetime, and 1 out of 4 Americans will die from cancer, making it the second leading cause of death in the US. Because cancer is so common, having several family members with cancer does not automatically mean that a family has an inherited (familial) form of cancer. In 80-85% of cancer cases, it occurs due to sporadic and environmental causes and does not have an inherited genetic basis. In order to determine whether the type of cancer occurring in a family is based on an inherited genetic susceptibility or if it is sporadic, careful collection and analysis of an individual’s and his or her family’s medical histories must be done. This is reviewed in the Familial Cancer section.

General Cancer Description

Cancer is the general name for a group of diseases where cells in an organ or tissue grow out of control. Normally, cells in the body have a very specific life span, in which they grow, copy themselves, divide, and die. As adults, our cells divide and replace themselves only as they become damaged and/or are destroyed. This is a normal process for maintaining our health and it is tightly controlled.

If control over growth is lost, cells divide much more often than normal. These excess cells form a mass that is called a tumor. There are two main types of tumors, benign and malignant:

• Benign tumors are confined to a few cell layers of one organ or tissue and do not spread (metastasize) to surrounding tissues or organs. These tumors are NOT considered cancerous or life-threatening, though they may need to be removed if they are causing damage due to their size or location.
• Malignant tumors are cancerous and possibly life-threatening. They spread to other sites in the body where they begin to grow and replace the normal tissue there, forming new tumors. This process is called metastasis. The tumor at a distant site is still named for the location of the primary tumor because all of the cells in both tumors are from the same primary tissue. For example, if breast cancer spreads to the liver, it is still referred to as breast cancer, not liver cancer. This is important because different types of cancers behave very differently in terms of how quickly they grow and metastasize and how they respond to treatment.

General Genetics Description

Our bodies are made up of millions of cells, which have structures located inside them called chromosomes. These chromosomes are packages of long strands of a chemical called DNA, which is the substance in every cell that controls and directs all its activities. Sections of the DNA strand make up genes, which are connected block-wise along the length of a chromosome. Genes can be thought of as discrete segments of information similar to chapters in an instruction manual. The body “reads” the DNA for information on how to make the substances that it needs to function correctly.

Each chromosome in a cell comes in a pair, one from our mother and one from our father. Because the information in our genes determines many of our characteristics, we appear to be a mix of the traits from both our parents. A typical person has 23 pairs of chromosomes in each one of his or her cells and because a person has two copies of every chromosome, this means that they have two copies of every gene.

Cancer and Genetics

The process of growth and living requires that new cells be made, either for growth or to replace damaged and dying cells. New cells are made during a replication process where the DNA in older cells is faithfully copied and then divided between two new cells. If the DNA becomes damaged before, during or after this process, our body has repair systems to fix it and make it as close to its original form as possible.

A cell becomes cancerous due to damage to its DNA. Most of the time when DNA becomes damaged, the body is able to repair it or the cell self-destructs. In cancer cells, the damaged DNA is not repaired or is misrepaired. If a non-repaired mistake occurs in a gene associated with cell division and growth, the cell might continuously make copies of itself and become cancerous. People can inherit a gene from one of their parents that has been damaged in this way, and this results in an increased risk for cancer. However, the majority of the time, a person’s damaged DNA isn’t inherited but rather becomes damaged by exposure to something in the environment, like the sun or smoking.

Cancer is predominately considered a disease of aging with the majority of new cases seen in people over 50 years of age. This allows for damage in DNA to accumulate. Due to improved medical care and increased lifespans, people are living longer than ever. Thus the longer a person lives, the more likely they are to develop damage in a gene controlling cell growth, which subsequently allows for the development of cancer.

Familial Cancer

Because cancer is so common in the general population, with 1 out of every 3 people expected to develop it in their lifetime, it is not uncommon for an individual to have a family member who has been diagnosed with cancer. Sporadic forms of cancer, those occurring without an identifiable cause, account for 80-85% of all cancers diagnosed. Likewise, only 15-20% of cancer cases are hereditary or are a familial form of cancer. Familial cancers are caused by genes, which are influenced by the environment, increasing an individual’s risk to develop cancer above the rate in the general population. Several factors lead to the suspicion of a familial form of cancer, such as:

• Cancer occurring at a relatively young age (often at less than 45-50 years of age)
• Several family members having the same time of cancer
• Cancer occurring as a new tumor bilaterally in the same organ (as in both breasts)
• Multiple types of cancer in the same person (for example, breast cancer and ovarian cancer occurring in the same person)
• Rare or unusual types of cancer (such as ovarian cancer or male breast cancer)

If these characteristics occur, a certain form of cancer may be running in a family. Currently, research has linked 5-10% of cancers to genes called predisposition genes.

Predisposition Genes

Predisposition genes are genes in which a change or mutation in the DNA sequence would make a person more likely to develop a certain disorder than someone without the change. However, someone who has a mutation in a predisposition gene is not guaranteed to develop the disorder, they are simply at a higher risk to do so. This is because other genes and the environment also play a role in the development of many disorders. Predisposition genes are also referred to as susceptibility genes.

Examples of predisposition genes related to cancer are BRCA1 and BRCA2, both of which are associated with breast and ovarian cancer. A woman with a mutation in either the BRCA1 or the BRCA2 gene is much more likely to develop breast or ovarian cancer than a woman who does not have a mutation. However, she is not guaranteed to develop either cancer in her lifetime. There are predisposition genes for disorders other than breast and ovarian cancer, such as for various forms of colorectal cancer and other disorders.

Genetic Testing

Genetic testing is currently available for several predisposition genes associated with cancer. Deciding to have genetic testing may be a difficult decision to make and has long-term ramifications. There are several issues to consider, including technical and psychosocial (emotional) aspects. It is a decision that should be thought out carefully. Some of the issues are discussed under Technical Issues Associated with Genetic Testing and Emotional (Psychosocial) Issues Associated with Genetic Testing.

Technical Issues Associated with Testing

Before genetic testing can be helpful or informative to an individual, a specific mutation needs to be identified in a family. For example, several members of a family may have breast cancer and may have had genetic testing for the BRCA1 or BRCA2 gene for which no mutations were identified. Further testing for BRCA1 or BRCA2 mutations in other family members would most likely be uninformative. Once a mutation has been identified within a predisposition gene, other members of the family can be tested for this specific mutation.

For the most informative testing, the mutation must first be found in an affected individual. If the person has genetic testing for mutations in a predisposition gene, their results can fall into three categories:

1. Positive result: The gene change that is detected in this person is associated with an increased risk for developing a specific type of cancer. This does not mean that they will develop that cancer, but that they are more likely to develop it than an individual in the general population.
2. Positive result of uncertain significance or an indeterminate result: This refers to a change in the gene that has not been specifically associated with an increased incidence in cancer. Thus, it is unclear if this specific gene change has clinical significance or not. Certain testing steps can be taken to try to clarify this result but the significance of the gene change may remain undetermined.
3. Negative result: A negative result for the first affected person tested in the family has unclear ramifications. They may still have a mutation in the predisposition gene that is not currently detectable by testing. Or they may have a mutation in a different predisposition gene that is not yet identified or for which there is no testing. This type of result is uninformative and does not allow for recalculation of an individual’s risk of having a predisposition gene mutation or of developing cancer in the future.

With a positive result in hand for a predisposition gene mutation, it may be possible to estimate the risk of other family members. At this time, anyone else who is tested could either have or not have the same gene change. If they have the gene change, they are at increased risk to develop that type of cancer. If they do not have the gene change that has been associated with the form of cancer in their family, they are assumed to have no increased risk to develop that type of cancer. This is a true negative result. Please note, this only lowers their risk to the general population risk, not below it.

Emotional (Psychosocial) Issues Associated with Genetic Testing

There are several psychosocial implications related to genetic testing. Some points to consider when making a decision about pursuing genetic testing are:

• Is this a time in your life in which you are emotionally able to handle this issue? This information cannot be unlearned, therefore, are you certain that this is information you feel is important to have now? Often it is easier to realize the periods in life when testing should NOT be pursued.
• How will this information affect the decisions you make in life? How would your decision-making change with a positive, negative, or indeterminate result?
• Do you have a support system in place to help with any emotional issues raised by genetic testing?
• How will this information affect other members of your family (your siblings or children)? How will this affect your relationship with other family members?

Possible Repercussions: Insurance and Employment Discrimination

All medical professionals are trained to maintain confidentiality. However, with any form of medical testing, there is no way to guarantee that test results remain private. In addition, concerns have been raised about the possibility of insurance and/or employment discrimination due to genetic testing. At this time, legislation has been passed in several states to prevent higher premiums or termination of coverage due to genetic testing results. This is not nationwide, however, and it does not cover life insurance, so genetic testing may impact coverage. There have also been documented cases of employment discrimination for cancer survivors. Because these are very serious issues, they need to be considered before genetic testing is undertaken.

Alternatives to testing

Even if someone is considered to be at increased risk for a form of cancer, they may not want to pursue genetic testing. If they still wish to take some action, other options are available. These include:

• Increased surveillance for the type of cancer they are at risk for. For example, a woman might have mammograms more often if her family appears to have a familial form of breast cancer.
• DNA banking: This involves extracting the DNA from a sample of blood and keeping it frozen for future use. This allows for testing at a later date and may be a better option for anyone who would like to know the information at a different point in time.