[2020-10-29] The role of genes in cancer
For those of you wishing to know more about cancer in general and hereditary breast and ovarian cancer in particular, BC Cancer has an excellent document on its site called Understanding Hereditary Breast & Ovarian Cancer – the BRCA genes. First published in 2004 and updated in 2014, it is a helpful complement to the e-learning module I told you about in my post on Genetic testing.
In reading this document, I realized that there was a lot about cancer I didn't understand. While healthcare professionals do a good job of telling you what disease you have and how they plan to treat it, they spend much less time explaining why you may have become ill in the first place. That's understandable and I don't question the focus on the knowns (diagnosis and treatment) over the unknowns (cause). However, as I face the prospect that my cancer is hereditary, I find value in better understanding what cancer is and how it occurs.
The first thing that struck me in the document is that all cancer is genetic but most is not hereditary. Perhaps it's been too long since Grade 13 Biology, but I mistakenly internalized that genes were inherited and therefore one's risk for certain diseases was determined at birth according to the gene-assigning lottery. In fact, genes can change over one's lifetime. The booklet opens with a short statement on the role of genes in cancer:
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.
My layperson's understanding of this is that a gene has a function. Among those functions are ones that control cell division. If a gene that controls cell division changes or mutates, it may no longer prevent a cell from dividing uncontrollably. This can lead to the development of a cancer. Cancer cells can infiltrate and destroy normal body tissue.
So cancer is caused by a gene gone haywire. Most frequently, these gene changes occur after a person is born and are neither inherited from parents nor passed on to children. The booklet states:
All cancers are 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 people are not born with these acquired gene mutations, they cannot pass them on to their children.
A graphic in the booklet identifies the source of cancers as sporadic (70-75%), familial (20-25%) or hereditary (5-10%). The document expands on inherited gene mutations:
A small number of cancers are 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 a mutation has it in every cell in his/her body, including some of 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 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.
The first two genes that were found to be responsible for some hereditary breast cancers and some hereditary ovarian cancers were BRCA1 and BRCA2. Notwithstanding the fact that BRCA is an abbreviation for breast cancer, these gene mutations can be implicated in other cancers, including ovarian cancer and prostate cancer.
Everyone is born with the BRCA genes, which provide the codes to control the division of cells in the breasts and ovaries. Everyone inherits one copy of the BRCA genes from their father and one copy from their mother. Even if one inherited copy of a BRCA gene has a mutation, the other normal copy can still do the job (see right-hand diagram below). The booklet explains:
Because we have two copies of every gene, a mutation in one copy of a BRCA gene in a breast or ovary cell does not cause a problem; the other copy can still produce the protein to control cell growth. A mutation must occur in both copies of the same BRCA gene in the same cell for the control to be lost and a cancer to develop.
This explains why someone can be a carrier of a BRCA gene mutation but never develop cancer.
The booklet describes various scenarios if a person inherits a BRCA gene mutation (see left-hand diagram below):
This person is born with a mutation in one copy of a BRCA gene and this mutation is present in every cell of the body. The other copy of that gene is normal and is able to "do its job". This person is a BRCA gene mutation carrier.
As a person ages, DNA mutations occur by chance, in different genes, in different cells. A woman who is born with 2 normal copies of the BRCA genes in every cell has to acquire a mutation in both copies of the same BRCA gene in the same breast or ovary cell for a cancer to develop. This is what happens in sporadic cancer.
If a mutation occurs by chance in the normal copy of a BRCA gene in a breast or ovary cell when a woman is a BRCA mutation carrier, the cell no longer has a working copy of that gene. The normal BRCA protein will not be made and a cancer may develop. That helps to explain why a woman who inherits a BRCA gene mutation is much more likely to be diagnosed with breast cancer or ovarian cancer than is a non-carrier. Hereditary cancer is also more likely to be at a younger age than the same kind of cancer in the general population. And there is a greater chance of having more than one separate cancer diagnosis (e.g. a new cancer in each breast).
Based on what I've read, heard and observed in my own family history, I believe that it's a toss up as to whether I am a carrier of a BRCA gene mutation. I intend to share my results, either way, as I increasingly see my mission with this blog as increasing awareness of ovarian cancer. Because the incidence of ovarian cancer in the general population is low (only 1-2%), many people—and I was one up until three months ago—know very little about the disease. However, given that there is no reliable routine screening test for ovarian cancer, the more people who know about the disease, its causes and its symptoms, the better.
