Yes, the BReast CAncer gene 1, or BRCA1, is a tumor suppressor gene. Every person has BRCA1 genes, which provide instructions for creating a protein that helps prevent cells from multiplying uncontrollably. This protein’s primary role is to maintain the stability of a cell’s genetic information, acting like a braking system to halt rapid cell division and prevent tumor formation. In its healthy state, the BRCA1 gene is a fundamental part of the cellular machinery that safeguards our DNA.
The Role of a Healthy BRCA1 Gene
The BRCA1 protein is involved in the complex process of DNA repair. Our cells are exposed to environmental factors, like radiation, that can cause daily damage to our DNA. One of the most severe forms of this damage is a double-strand break, where both strands of the DNA double helix are severed. If not properly mended, these breaks can lead to significant genetic problems, and the BRCA1 protein is central to this repair process.
The BRCA1 protein acts as a scaffold at the site of DNA damage, interacting with other proteins to form a complex that carries out repairs. It is involved in a high-fidelity repair pathway known as homologous recombination. This process uses an undamaged copy of the DNA as a template to make a precise repair, preventing harmful mutations from being passed on.
Besides its role in mending DNA, the BRCA1 protein also functions as a checkpoint regulator in the cell cycle. When DNA damage is detected, the protein can signal the cell to pause its division process. This pause gives the cell time to fix the DNA errors before it proceeds to replicate. If the damage is too extensive to be repaired, the protein can also trigger cell death to eliminate cells with potentially dangerous mutations.
Impact of BRCA1 Gene Mutations
A harmful mutation in the BRCA1 gene often results in a short, non-functional protein or prevents the protein from being made at all. Without a functional BRCA1 protein, the cell’s ability to repair double-strand DNA breaks is compromised. This disruption forces the cell to use less accurate backup systems, which are more prone to making errors during repair.
This failure in DNA repair leads to an accumulation of genetic mutations over time. As a cell divides, these errors are duplicated and passed to new cells, causing a state known as genomic instability. This instability is a characteristic of many cancers, as the cell’s genetic blueprint becomes chaotic, eventually leading to the uncontrolled growth that defines a tumor.
A BRCA1 mutation is not a direct cause of cancer but instead creates a cellular environment where cancer is more likely to develop. The loss of the BRCA1 protein’s function removes a safeguard that protects the genome. This inherited vulnerability increases the likelihood that further genetic damage will persist, potentially leading to a malignant tumor.
BRCA1 Mutations and Cancer Risk
An inherited BRCA1 mutation elevates a person’s lifetime risk of developing certain cancers, most notably hereditary breast and ovarian cancers. For women with a harmful BRCA1 mutation, the lifetime risk of developing breast cancer can be as high as 80%. The risk for ovarian cancer is also increased, with a lifetime risk estimated between 35% and 60%.
The influence of BRCA1 mutations extends beyond breast and ovarian cancers, increasing the risk for several other types. These include:
- Male breast cancer
- Pancreatic cancer
- Prostate cancer
- Colon cancer
Having a BRCA1 mutation does not guarantee that a person will develop cancer, and many individuals with the mutation live their entire lives without a diagnosis. Other genetic, environmental, and lifestyle factors also determine a person’s overall risk. The mutation represents a strong predisposition, not a certainty.
Inheritance of BRCA1 Mutations
BRCA1 mutations follow an autosomal dominant inheritance pattern, meaning a person only needs to inherit one copy of the mutated gene from one parent to have an increased cancer risk. Since the gene is on a non-sex chromosome, it can be passed from a parent to a child of either sex. A parent with a BRCA1 mutation has a 50% chance of passing it to each of their children.
This inheritance pattern explains why cancer can appear in multiple generations of a family, a concept explained by the “two-hit hypothesis.” A person with a hereditary BRCA1 mutation is born with the first “hit” in every cell: one non-functional copy of the gene. They still have one healthy, working copy of the BRCA1 gene in each cell, which is sufficient for normal function.
Cancer develops if the second, healthy copy of the gene becomes damaged in a specific cell, such as in the breast or ovary, during a person’s lifetime. This “second hit” leaves the cell with no functional BRCA1 protein, disabling its DNA repair capabilities. This explains why the risk is increased but not absolute, as this second event must occur for the protective function to be lost in a cell.