Genetics of Breast Cancer: Risk Genes According to Recent Studies

Genomic studies have come a long way since its conception. Back then, genomics was only a field used for laboratory experiments. Today, scientists are now eyeing the use of genomics in medicine. This would allow for a clearer diagnosis of a person’s disease through their genome. As a current application of genomics in research, scientists use them to study similarities in the genes between patients with the same disease. Effectively, this tells us the root causes of such a disease in terms of genetics. In this discussion, we will try to uncover breast cancer through the scope of its genetics.

The Role of Genetics in Breast Cancer

Generally, cancer cells appear due to an error in the production of our cells. Our body has certain programs for this production, which run through its genes. To keep the program working correctly, our body imposes functions that regulate cell production, such as DNA repair.

Like most other kinds of cancer, a person’s genetic history also affects breast cancer. This history may pertain to one’s family background and the diseases they acquired throughout life. According to a 2007 study, women with breast cancer who have first- and second-degree relatives are more likely to develop the disease.

The way this likelihood works is through inheritance of mutated genes. A gene may mutate because of aging or through mutagens such as radiation. If one inherits a mutated gene, the gene can lose its supposed function. In most cases, tumor suppressor genes are the ones that mutate.

Established Risk Genes For Breast Cancer

There are currently two established risk genes for breast cancer, and you can think of them as working in a pair. This pair is the BRCA1 and BRCA2, short for BReast CAncer genes 1 and 2. They basically have the same purpose of suppressing tumor formation. 

We inherit these genes from each of our parents. When someone inherits a single mutated BRCA gene, they are at a greater risk of breast cancer. However, if the other gene mutates throughout their lifetime, the cells containing the two mutated BRCA genes become cancer cells. This leads to a higher risk of breast cancer. 

Although called the breast cancer genes, the BRCA genes do not only concern the cells in the breast. Each cell in our body contains this gene. And when the genes in the cells of different areas of our body mutate, they can also cause cancer in those areas. Because of that, both BRCA1 and BRCA2 are also risk genes for ovarian cancer. 

Specifically for BRCA2, mutations in the gene can increase the risk of the pancreas, male breast, and prostate cancer. A 2019 journal article goes into the details of the BRCA1 and BRCA2 mechanisms. It appears that while mutations in either the BRCA1 and BRCA2 can cause a higher risk of cancer, a mutation in BRCA2 can already promote cancer cell production. 

Other High-Risk Genes For Breast Cancer

There are other genes in our bodies that can affect the way we interact with cancer cells. Some of them are also tumor-suppressing genes like the BRCA genes. They also have other consequent diseases aside from increased risk for breast cancer. 

For the following discussion about the other high-risk genes, we will base our information on a review study collated in 2019. While the study explores different genes in terms of its degree of risk, we will only be going through the high-risk genes. These high-risk genes account for around 20% of the familial risk of breast cancer.

TP53 Gene

This gene is responsible for creating a protein named tumor protein p53, hence the name TP53. While by name, the protein p53 is a tumor suppressor, it also has a function in cell cycle regulation, DNA repair, programmed cell death or apoptosis, and metabolism. Because of this, this gene is a key factor for many tumor-forming diseases.

Medical professionals often associate this gene with Li Fraumeni Syndrome. This happens when a mutation happens in the TP53 gene. Consequently, the individual will become at risk of several cancers such as breast, bone, soft tissue, blood, brain, and adrenal gland cancer. This comes with a staggering 100% lifetime cancer risk for women and a 73% risk for men. 

CHEK2 Gene

The CHEckpoint Kinase 2 gene is responsible for important interactions with the tumor-suppressing genes TP53 and BRCA1. Because of this, we can see some connections between CHEK2 mutations and Li Fraumeni Syndrome.

A certain mutation of the CHEK2 gene called the CHEK2*1100delC variant appears to be more frequent in Northern and Eastern Europe. This specific variant can increase the risk of contralateral breast cancer by 3.5 times. Survivability from the cancer also diminishes because of this mutation. 

Other Genes

The four genes mentioned above are the more extensively studied genes that affect breast cancer. Although scientists still require more research, the following genes are also likely to be of high risk:

  • PTEN: a tumor-suppressing gene encoding a protein with multiple functions.
  • STK11: another tumor-suppressing gene with other roles in cell cycle regulation and apoptosis.
  • CDH1: this gene encodes a protein important in cell-to-cell adhesion and cell invasion suppression. 
  • NBN: responsible for a protein complex that plays a role in detecting and early processing of damage in the DNA.
  • PALB2: this gene encodes a protein with an important responsibility in DNA repair.
  • ATM: the Ataxia-Telangiectasia Mutated gene can cause neurodegenerative disorders when it mutates.
  • NF1: the NeuroFibromin 1 gene produces a tumor-suppressing protein. 

All these genes show a pattern of mutations in the tumor-suppressing gene having drastic effects on breast cancer. We also see a lot of proteins responsible for regulations in the cell cycle, apoptosis, and DNA repair. These are all important to ensure that the replicated genes in the cell are correct. 

If you examine these other genes further in the 2019 review study, you can surmise a few more connections between the different genes and the effects they can bring to a patient. In a way, what we are doing reflects the future of genomics as our technology advances. In the near future, diagnosing diseases such as cancer will become easier as conjectures from our genetic family history become more accessible. 

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