Do I have an increased risk of breast cancer?

Breast cancer is the most commonly diagnosed form of cancer in Dutch women. Most tumors arise due to dumb luck but a significant portion of tumors arise because of genetic predisposition. 5 to 10 percent of all breast cancers are caused by genetic predisposition. This means that someone has inherited a mutation in her genetic material from her parents which increases risk of a tumor. A lot of research has been done in this field and currently multiple tests can be done to determine if someone has inherited a genetic predisposition.

Before genetic tests are done there are other factors to be considered, like family history. Looking into someone’s family history does not mean asking questions like; ‘Are your parents divorced?’ or ‘Do you have any siblings?’. But it goes into their medical history. There might be a pattern of disease in a family or may be a family member who carries a known mutation. This test goes as far as 3^rd degree relatives. 3^rd degree cousins share the same great-great-grandparents. If someone’s family history indicates an increased risk of cancer they can consult a medical oncologist for genetic testing.

To understand how a mutation in our genetic material is possible you have to know how it is stored and expressed. Genetic material is stored in DNA which can be transcribed into RNA and subsequently translated into proteins. DNA is stored in something called chromosomes. Human cells contain 46 chromosomes, 23 pairs. From each pair one chromosome comes from the mother and one from the father. In a single chromosome countless genes are encrypted. Chromosome exist of series of base pairs. There are 4 bases, Adenine (A), thymine (T), guanine (G) and cytosine (C). These form 2 sets of base pairs: AT and GC. The order in which these base pairs are organized in a chromosome determines what protein is made. A mutation in your DNA means that a base or base pair is replaced or deleted. This can lead to formation of a different, non-functional protein or no protein at all.

I’d like to talk a little bit about BRCA genes, notorious breast cancer genes. There are 2 kinds, i.e. BRCA1, located on chromosome 17, and BRCA2., located on chromosome 13. BRCA1 and BRCA2 are responsible for 90% of all hereditary breast and ovary cancers. BRCA1 and BRCA2 are tumor suppressor genes and normally protects cells from becoming cancerous. If tumor suppressor genes harbor a loss of function mutation they cannot suppress cancerous cells anymore, and the risk of tumor formation increases.

In BRCA genes different kinds of mutation can occur. Not all mutations are harmful and cause an increased risk of cancer. In some mutations the base pair sequence is altered but this does not effect protein production and/or function. However, a deleterious mutation is often considered very harmful. In a deleterious mutation one, or more, base pairs are removed. This can have multiple consequences for protein production. This can result in a protein not being made at all, or being made and not being functional or being functional but not preforming the right task. In a cell no single process works on it’s own, everything works in a network. So if a protein is depleted from this network it can result in a malfunctioning network and tumor formation.

DNA tests investigate the base pair sequence of someone whose family history indicated an increased risk of breast cancer and compares it to a database. This database contains information on the ‘normal’ sequence’ and known mutations in the genes. DNA used for the tests can be collected from blood or from saliva and are obtained by an oncologist. All cells in your body contain all genetic material but not all genes are expressed. So hypothetically all cells can be used to perform this test. Blood and saliva are most often used because they are easily accessible. A medical geneticist preforms the actual genetic test. The base pair sequence of the BRCA genes are examined by a technique called Next Generation sequencing. If the test indicates a positive result for a harmful mutation this means that someone has an increased risk. This is when precautions can be taken. Precautions like regular screenings to catch a tumor in an early stage and in cases of extremely high risk one can have their entire breast removed.

This genetic testing has its advantages but also its disadvantages. It can help in early discovery and treatment of cancers but it can also lead to genetic discrimination by health care insurance companies. I am very interested to learn what your stance on genetic testing is and whether you had experience with it. Let me know in the comments below.

By Marieke van Leeuwen, October 2015