Cancer Genetics

In order to discuss a tendency or genetic predisposition to cancer, it is important to understand the basics of genetics. The information on this Web site is meant to be an introduction to genetics. Please contact your physician or e-mail us if you have any questions about some of the information presented on this Web site.

Inherited Versus Sporadic Cancer
Genetics 101

Cancer and the Environment
Patterns of Inheritance

INHERITED VERSUS SPORADIC CANCER

The majority of all cancer occurs sporadically, by chance. Cancer is a very common disease in the United States, and 1 in 3 individuals will develop some type of cancer in their lifetime. Cancer is a disease where cells of the body change and grow rapidly. These changed cells can grow out of control and form a tumor, which can then go on to spread throughout the body. Many different factors may cause normal cells in the body to change and grow out of control.

These factors include environmental exposures (exposure to chemicals, radiation), hormonal factors (levels of different hormones in the body), dietary habits, and inherited genetic factors as well as others. Only 10% of all cancers are associated with inherited genetic factors. This means the majority of cancer diagnoses (90%) are not considered hereditary. Research is continuously exploring the non-inherited factors (environment, diet, hormones) to try to determine the cause of most cancers, but unfortunately, the actual cause of most cancer is still unknown.

The human body is composed of thousands of cells. Our genetic information is coded on structures called chromosomes that are contained in every cell. Humans should have 46 chromosomes total. Twenty-three chromosomes are inherited from the mother, and an equal number (23) are inherited from the father. This is why each individual has traits from both sides of the family. Every one of the 46 chromosome contains hundreds of genes. Each gene codes for a protein that the body requires for normal growth and development.

It may be useful to consider the following analogy. Think of each chromosome as a library, and each gene as a book (every library contains hundreds of books). Consider every book in the library to be a large recipe book. Each recipe book contains instructions on how to cook a meal. Chromosomes contain genes, and each gene contains the instructions for building a specific protein. If there is a mistake in a recipe (for example, an extra or missing ingredient), you may not be able to create the dish that you had anticipated. If there is a mistake in a gene, the body may not be able to produce the specific protein that gene codes for. A mistake in a recipe might hardly be noticeable in the final dish, or it might completely ruin the dish, and therefore, potentially impact the entire meal the dish was supposed to go with. A mistake in a gene may not affect the coded protein at all, or it might have a significant impact by creating a non-functional (non-working) protein. If this protein is needed to work with other proteins, those other proteins can also be affected.

Human beings have 46 chromosomes in most cells in the body. They are inherited in 23 pairs, one of each pair is inherited from the mother, one of each pair from the father. The first 22 chromosomes are numbered one through 22, biggest to smallest. The 23rd pair of chromosomes are the sex chromosomes, labeled X or Y. Females have two X-chromosomes (XX), and males have one X and one Y chromosome (XY).

DNA (deoxyribonucleic acid) is the chemical structure that encodes our hereditary information. DNA can be thought of as a string of genes arranged together on a chromosome (or, in continuing the above analogy, shelves of books in a library). Based on current research, it does not appear that genes that are located next to each other necessarily have anything to do with one another. For example, a gene related to eye color may be between a gene for diabetes, and a gene for height. Also, although several genes may be involved in creating proteins that will eventually interact with one another, these genes most likely are not next to each other, and in fact may be located on completely different chromosomes altogether.

There is where our library analogy doesn't quite fit. Most libraries arrange books with similar topics together. However, if we are thinking of our chromosomes as being libraries, to us these libraries would look "out-of-order", since books with similiar topics may be scattered anywhere throughout the library. This is partially why genetics is so complicated. Even if we can identify one gene that is related to height (for example), a different gene for height might be located on completely different shelf in a totally different library. The Human Genome Project is trying to create a "card-catalogue" of sorts, so that eventually a researcher interested in the genes associated with height will be able to look up exactly where all of the genes related to height are- without having to search through various different libraries to find them.

It is also important to realize that since we have two copies of each chromosome (one inherited from the mother, one from the father), we also have two copies of each gene. A mistake in a single gene in a cell may not have an affect (on the cell or the person) if the other copy of that gene pair in the cell is still working correctly.

The main concern in genetics is the presence of genetic mistakes, or mutations in the DNA. If a mutation in the DNA sequence leads to a non-working protein product, or stops the protein from being produced at all, this may lead to a symptomatic condition in the individual.

It is believed that the majority of genetic mutations occur spontaneously through errors in the replication (copying) and repair of DNA. Every time our body creates a new cell, it must copy all of our genetic information into that new cell. Every time our genetic information is copied, there is the potential for the cell to make a mistake during the copying process. However the body is prepared for these mistakes, and actually has a system in place to repair many genetic mistakes as they occur. Unfortunately though, occasionally a mistake will slip through the repair system.

Although that one mistake may not cause a problem immediately, every cell that is copied from this new cell will also have that same mistake. If additional mistakes occur in the future of the cell, the buildup of many mistakes may result in a major problem for all of the cells that contain those errors. A mutation arising in most cells in the body will not be passed on to the next generation, however if the mutation occurs in an egg or sperm cell, it can be passed on to the next generation. If left unrepaired, mutations in DNA may have serious implications for an individual, and/or later generations.

CANCER AND THE ENVIRONMENT

Recent research has given us a better understanding of the genetic factors involved in cancer, however it is important to recognize the environmental component involved in the development of cancer.

Environmental factors are obvious in some forms of cancer, such as lung cancer in individuals who smoke or work near asbestos. Other types of environmental exposures, such as radiation, diet, etc., have also been suggested to have an association with increased risk for certain types of cancer. However in the majority of cancers, environmental and genetic components are both involved in a complex, multifactorial (many factor) interaction which is yet to be fully understood. Current research is aimed at trying to help sort out these factors.

PATTERNS OF INHERITANCE

Autosomal Dominant Inheritance

Autosomal dominant inheritance is associated with many different conditions. The word autosomal refers to the fact that the condition is caused by a gene that is on an autosome. An autosome is any chromosome that is not a sex chromosome, i.e. all of the chromosomes numbered 1-22. Autosomes are inherited from both mothers and fathers, and are passed on to both sons and daughters. In a family with an autosomal condition, we would expect to see (approximately) equal numbers of males and females with the condition. Dominant inheritance refers to the fact that only ONE mutation in one pair of genes is necessary to cause the condition associated with the genetic alteration. Since humans have two copies of every gene, any individual who has an autosomal dominant condition has a 50% chance of having a child (male or female) who will also have the condition.

Autosomal Recessive Inheritance

Autosomal recessive inheritance is associated with many different conditions. The word autosomal refers to the fact that the condition is caused by a gene that is on an autosome. An autosome is any chromosome that is not a sex chromosome, i.e. all of the chromosomes numbered 1-22. Autosomes are inherited from both mothers and fathers, and are passed on to both sons and daughters. Thus, in a family with an autosomal condition, we would expect to see (approximately) equal numbers of males and females with the condition. Recessive inheritance occurs when BOTH genes of a pair have a mutation in order to produce the condition. If only one gene in the pair is changed, the individual would not be expected to have any signs or symptoms of the condition. However, a person with a single changed gene is called a carrier, and may have a child affected with the condition if the other parent is also a carrier of the same condition.

X-Linked Recessive Inheritance

X-linked recessive inheritance is also associated with many different conditions. The word X-linked refers to the fact that the condition is caused by a gene that is on the X chromosome (the 23rd chromosome pair consists of the X and the Y-chromosomes). Females inherit two X-chromosomes, one each from the mother and father. Males inherit one X chromosome (from the mother) and one Y chromosome (from the father). Recessive inheritance occurs when BOTH genes of a pair have a mutation in order to produce the condition. Since a female has two X chromosomes, if she has a mutation on one of her X chromosomes but a working gene on her other X chromosome, she will not have the condition. A female in this situation would be considered a carrier. Since a male has only one X chromosome, he has only one copy of each gene on that chromosome. Therefore, if one of the genes on his X chromosome has a mutation, he will have whatever condition is associated with that mistake.

Multifactorial Inheritance

Multifactorial inheritance is an interaction between many genes with possibly additive effects and environmental components. Multifactorial inheritance can be caused by the expression of many genes, the interaction of several genes, or the interaction of a gene or genes with other environmental factors. With multifactorial inheritance, it is difficult to determine the precise cause of the condition because it is a net effect of genetic, environmental and lifestyle factors that may influence an individual’s susceptibility to develop the condition.