Cancer is a genetic disease, that means it is caused by mutations occurring in certain genes (modifications in the genetic sequence) that play a key role in controlling normal cell growth and division.
DNA is the molecule that stores the genes that make up our genetic code. Genes carry the instructions for producing proteins, which are the molecules that carry out most of the tasks within our cells. Genes affected by cancer may have different functions such as controlling cell division, repairing any damage that occurs in the genetic code or regulating programmed cell death.
There are different types of DNA mutation. Genetic code is comprised of a sequence of four different molecules called nucleotides (A, C, G and T). Some mutations only affect one nucleotide. For example, a nucleotide may have been replaced by another one or it may be totally absent. Other mutations involve larger sections of DNA and can include rearrangements, deletions or duplications of long segments. In other cases, the genetic alteration does not necessarily affect the DNA sequence. This is known as an epigenetic mutation. Thus, the addition or elimination of chemical markers, such as the methylation of DNA, can influence the expression of a specific gene.
In most cases, the genetic changes that lead to cancer are usually acquired throughout a person’s lifetime as a result of errors that occur in their genetic code (DNA) when their cells divide or suffer damage due to exposure to carcinogenic substances such as chemicals found in tobacco smoke, ultraviolet rays or certain foods. Genetic changes that occur after conception are called somatic (or acquired) mutations and they depend heavily on age and environmental factors (e.g., diet, exposure to the sun, sedentary lifestyle, obesity).
In a smaller percentage of cases, the genetic modifications that produce cancer are inherited from parents or grandparents if there are mutations in the cells linked to reproduction (eggs and sperm). Such modifications, called germline mutations, are subsequently found in all of the individual’s cells. Therefore, some people are born with a predisposition for developing cancer as all of their cells carry a certain mutation. This situation is known as hereditary cancer, in which case the cancer tends to develop at earlier ages and there is usually a history of cancer in their family.
Cancer cells generally acquire a large number of genetic changes that differentiate them from normal cells. These mutations are usually specific to a certain organ. Some tumours are the result of mutations, but they are usually caused by cancer and uncontrolled cell division. Therefore, as the cancer continues to grow, further changes will occur. Even the cancer cells within the actual tumour can also present different genetic changes. For certain cancers, the study of genetic alterations associated with cancer (somatic study) is currently used to develop a prognosis and predict the response to certain target-specific cancer drugs. This process forms the basis for the personalisation of cancer treatment.
Hereditary cancer syndromes
Inherited genetic mutations correspond to 5%–10%of all cases of cancer. Over 50 different specific genes have been reported to bear an association with hereditary cancer. This means people who carry these mutations have a predisposition to certain types of cancer. It is important to highlight that most carriers of these genetic alterations will not usually develop cancer; in fact, there are several factors, both environmental and ones due to changes in other genes, that influence its onset.
The genetic tests for hereditary cancer syndromes can detect whether a person has one of these mutations. Nowadays, these tests simultaneously analyse for the genes associated with a specific type of cancer (next-generation sequencing gene panel). The genetic study identifies the causative mutation and subsequently establishes if any family members who have not yet developed the disease have inherited the same mutation.
Genetic testing is only indicated when an individual has a specific type of cancer that is known to respond positively to therapy with target-specific drugs and when the doctor has decided to start treatment with the given drug.
The key in the diagnosis of hereditary cancer is prevention. As such, healthy carriers of gene mutations should implement prevention efforts to avoid or ensure the early detection of the onset of cancer. The interpretation of genetic studies, genetic counselling for people with a suspected hereditary cancer and follow-up in families with hereditary cancer should all be conducted by multidisciplinary teams in specialised centres.
Some examples of hereditary cancer are Lynch syndrome (caused by germline mutations in DNA repair genes, MLH1, MSH2, MSH6, PMS2), hereditary ovarian and breast cancer (caused by mutations in the BRCA1 and BRCA2 genes) or Li–Fraumeni syndrome (due to mutations in the TP53 gene).