Cancer and heredity

Some people are predisposed to develop cancer. Mutations in genetic material that increase a person’s chances of developing cancer can already be present at birth. Researchers are closely examining these mutations to learn more about how cancer begins to develop.

Mutations that increase cancer risk

DNA is found in all cells in our body and is divided into genes. Throughout our life, changes occur in our DNA, which we call mutations. These mutations are usually harmless, but when they occur in particular genes they can lead to cancer. Sometimes a person has mutated genes at birth because those mutations ‘run in the family.’ For example, you can be born with mutations in the so-called ‘breast cancer genes’ BRCA1 and BRCA2. This is known to tremendously increase risks for breast and ovarian cancers, but in many other cases of familial cancer it is not clear which mutated gene is responsible. LUMC researchers are studying this issue from a variety of different angles.

Searching for other genes

‘At LUMC we see people with a certain type of tumour occurring in their family more often than you would expect by chance. That’s the case for about 5 to 10 per cent of the cancer patients,’ says Christi van Asperen, professor of Clinical Genetics. ‘So we study whether in that family a mutation occurs in a known gene that can increase a person’s risk for cancer. We find these mutations in approximately a quarter of the families. For this reason, in national and international studies we look for genes that play a role in the development of hereditary breast and ovarian cancer. That entails ensuring that you make a distinction between harmless mutations and those at the root of the disease. We can use this knowledge to correctly inform people with a high incidence of cancer in their family about their chances of developing the illness.’

Repairing broken DNA

Marcel Tijsterman, who is professor of Genome Stability, studies heredity at the molecular level. ‘We look at what exactly happens in the cell when a gene mutates: How does the changing of the DNA in a cell cause a higher risk for cancer? For example, when there are mutations in BRCA1 and BRCA2, breaks in the DNA do not repair well. This facilitates additional mutations in other genes, and this snowball effect increases one’s risk for cancer. ‘We are also studying other genes involved in repairing damage to the DNA and the extent to which they contribute to hereditary and sporadic cases of cancer. In this way we will come to a complete understanding of the development history of this complex disease,’ Tijsterman explains.

The tumour’s passport

Cancer cells can divide uninhibitedly, but they often also have properties that make them vulnerable. 'The mechanism behind the development of cancer tells us more about those weak spots. We look for strategies to exploit these weaknesses in the treatment,’ Tijsterman explains. He thinks that in the future, researchers will be able to determine a tumour’s entire genome, a tumour’s ‘passport’, so to speak. In this way, cancer patients can receive a custom treatment that is specifically tailored for their tumour.’

Hebon, research on hereditary breast and ovarian cancer (in Dutch)