DNA provides the written blueprints for our bodies. DNA is organized into small sections known as genes; there are about 20,000 distinct genes in humans, and we have two copies of each gene, one inherited from each parent. The building blocks of DNA are known by the letters A, C, T, and G, so a stretch of DNA might be recorded as something like …AGCGCCTAGTACG….
The DNA in a gene is read in the cell by a pair of processes known as transcription and translation to create proteins. Sometimes, genes have spelling errors, for example, where a T is replaced with a C. These misspellings are called mutations, variations, or variants. These misspellings can prevent the translation process from creating the protein correctly, resulting in a less effective protein or no protein at all.
Some mutations we are born with, meaning that one of our parents had it, or they happened when the egg or sperm were created. These are called germline mutations—germ as in germinate, not germ like virus or bacteria—and will be the same in all the cells of the body. (Our study looks at these mutations and other variations in germline DNA.) There are other types of mutations that happen during our lives. As our bodies get older, our system that reads our DNA gets older too, and will sometimes allow mistakes in copying DNA to go uncorrected. Factors such as the sun, radiation, environmental pollutants, harmful components of diet, and so forth (geneticists refer to all these things as the environment) can also cause the DNA within our cells to get errors. These types of errors, known as somatic mutations, are acquired throughout life, but will not be found in all the body’s cells, and are not passed on to offspring.
So what are BRCA1 and BRCA2?
BRCA1 and BRCA2, which stand for BReast CAncer susceptibility, are two genes that play a crucial role in preventing cancer by acting as tumor suppressors. When functioning correctly, tumor suppressor genes produce proteins that fix DNA-copying errors in the cell and prevent cells with spelling errors from growing uncontrollably. Mutations in either BRCA1 or BRCA2 lead to malfunctioning proteins that may result in uncontrolled cell growth, which can create a tumor. The biggest impact of mutations in the BRCA genes is in the development of breast cancer in both women and men, but they can also increase the risk of other cancers, such as ovarian, pancreatic, and prostate cancer.
What does it mean to have an inherited BRCA1 or BRCA2 mutation?
Some people will acquire a somatic genetic mutation in BRCA1 or BRCA2 during the course of their lives due to environmental factors. This type of single mutation may not result in cancer, since typically more than one mutation is required to significantly impact the function of the resulting protein. People with a germline BRCA1 or BRCA2 mutation already have one mutation from birth, so if they acquire another during their lives due to environmental factors, they then have two mutations and will be much more likely to develop cancer.
This phenomenon is referred to as the two-hit hypothesis. For those with a germline mutation, the first ‘hit’ is the inherited or germline mutation, while the second ‘hit’ is an acquired mutation in the other copy of the same gene, which can occur from regular interaction with the environment. This second ‘hit’ can completely disable the ability of BRCA1 or BRCA2 to prevent tumors, leading to cancer. This is why having an inherited mutation in BRCA1 or BRCA2 gives an increased, but not 100%, risk of getting cancer in your lifetime.
Looking for more?
There’s a nice overview of BRCA1 and BRCA2 written by the University of Pennsylvania’s Basser Center for BRCA. If you are personally affected by variants in BRCA1 or BRCA2, and you are not already under the care of appropriate medical professionals, you can find a local genetic counselor here: https://findageneticcounselor.nsgc.org/