How Inherited Gene Mutations Cause Cancer
As a person ages, DNA mutations occur by chance, in different genes, in different cells. If a chance mutation occurs in the normal copy of a BRCA gene in a cell of a “carrier”, that cell no longer has a working copy of that gene. The BRCA protein will not be made in that cell and the cell may begin to divide. This may allow a cancer to develop.
With a mutation in one copy of a BRCA gene in every cell already, as described earlier, it only takes one chance mutation in the other copy for the stage to be set for a cancer. A person who is born with two normal copies of the BRCA genes in every cell would have to acquire a mutation in both copies of the same gene in the same cell for that process to start..
Looking at a single chromosome, DNA is arranged in units called genes. Genes direct the growth, development and function of the human body; everything from eye colour, to height, to how often cells divide. We have approximately 30,000 different genes, each in a specific place on a specific chromosome. Since we have two copies of every chromosome, we also have two copies of every gene - one copy from each parent.
The gene changes that affect function are called mutations.
Every cell in the human body contains a chemical substance called deoxyribonucleic acid (DNA). DNA is packaged into structures called chromosomes. Each human cell contains exactly 23 pairs, or a total of 46 chromosomes. The 23rd pair determines our sex – females have two “X” chromosomes, and males have one “X” and one “Y” chromosome.
Chromosomes come in pairs because one set of 23 chromosomes comes from the mother in the egg and the other set comes from the father in the sperm. When a sperm and an egg unite, they form a new cell with 46 chromosomes. When this cell (the fertilized egg) divides, all 46 chromosomes are copied and passed on to every cell that eventually makes up a new human being.
This means that a person who carries a gene mutation is much more likely to be diagnosed with cancer than is a non-carrier. Cancer is also more likely to develop at a younger age than the same kind of cancer in a non-carrier and there is a greater chance of having more than one separate cancer diagnosis. For example, the chance of developing bilateral breast cancer after unilateral breast cancer approaches 50% for individuals carrying a BRCA mutation, compared to 5-10% for those who are non-carriers.
Each gene has a specific function in the body. Some genes control cell division. When mutations occur in these genes, a cell may begin to divide without control. Cells that divide when they are not supposed to may eventually become a cancer.
All cancer is the result of gene mutations. Mutations may be caused by aging, exposure to chemicals, radiation, hormones or other factors in the body and the environment. Over time, a number of mutations may occur in a single cell, allowing it to divide and grow in a way that becomes a cancer. This usually takes many years, and explains why most cancers occur at a later age in life. Because most people are not born with these ''acquired'' gene mutations, they cannot pass them on to their children.
An increasing number of cancers are known to be hereditary. This means that they are related to a specific gene mutation that is passed down (inherited) in a family. A person who is born with this type of mutation has it in every cell in his/her body, including the eggs or sperm. This means it may be passed down to the next generation. Individuals who inherit such gene mutations have a higher risk of developing certain forms of cancer as compared to the general population. Inherited gene mutations help to explain why, in some families, we see more people than expected with certain kinds of cancer.
Research has found some of the genes that help to explain specific patterns of hereditary cancer in some families. Other genes, with varying degrees of significance, will continue to be identified in the future. By studying families with inherited gene mutations, researchers know of features that may help to identify other families at risk for hereditary cancer. Because this type of hereditary cancer is a relatively new science,most of the research available to date is about the first inherited genes for breast cancer that were discovered, BR(breast)CA(cancer)1 and BRCA2. They will be the subject of the rest of this page, although the information can apply to allrisky genes.