Gene involved in colorectal cancer also causes breast cancer

12 February 2019• PRESSRELEASE

Rare mutations in the NTHL1 gene, previously associated with colorectal cancer, also cause breast cancer and other types of cancer. Researchers from Radboud university medical center, Leiden University Medical Center and the Princess Máxima Center in the Netherlands report this new multi-tumor syndrome, in collaboration with international colleagues, in Cancer Cell.

Previously, reseachers from the Radboud university medical center and colleagues showed that mutations in the NTHL1 gene lead to intestinal polyps that may develop into colorectal cancer.However, they observed that patients with mutations in this gene often have other types of cancer as well. In their publication, the researchers describe 17 families in which members of a single generation had mutations in the NTHL1 gene. Half of these patients developed various types of cancer during their lives, with breast cancer being particularly common. "This study makes it clear that also in families where cancers occur more frequently in one generation, recessive mutations in NTHL1 can also be thought of as a cause", says Maartje Nielsen, clinical geneticist at the LUMC.

Mutations in the NTHL1 gene are very rare. A mutation in the NTHL1 gene only leads to cancer when the mutation is inherited from both parents. The researchers estimate that this is the case in about 1 in 115,000 people. The syndrome is difficult to detect because it only leads to cancer in a single generation of a family.

Improved characterization of patients with mutations in the NTHL1 gene may lead to better assessment of their lifetime risk to develop certain types of cancer. "It is important for patients to be aware of their risk for breast cancer and also for me as a physician, so I can make recommendations," says Maartje Nielsen, clinical geneticist at the Leiden University Medical Center. She recommends that patients with mutations in the NTHL1 gene should be screened for various types of cancer, including colorectal cancer and breast cancer.

Mutation pattern

The researchers used a new method to determine that NTHL1 mutations also cause breast cancer and other types of cancer. This method is based on the fact that mutations in the NTHL1 gene cause a specific pattern of mutations in the DNA of the tumor. 

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