Rare mutations in the NTHL1 gene, previously associated with colorectal cancer, also cause breast cancer and other types of cancer. Researchers report this new multi-tumor syndrome, in in Cancer Cell.
Previously, researchers 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.
NTHL1 is involved in DNA repair. It recognizes a specific form of DNA damage. If a mutation occurs in the NTHL1 gene, there is no NTHL1 protein. Consequently, this specific form of DNA damage is not recognized and not repaired, leading to an accumulation of mutations, which causes cancer. Due to mutations in the NTHL1 gene, errors in the DNA where a 'C' is replaced by a 'T', are not corrected. These errors occur at specific locations in the DNA, resulting in a recognizable mutation pattern.
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 another author and recommends that patients with mutations in the NTHL1 gene should be screened for various types of cancer, including colorectal cancer and breast cancer.
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. Because this pattern only occurs in tumors of patients with an NTHL1 mutation, and not in tumors from other patients, the researchers were able to link this pattern to the disrupted NTHL1 gene.
In the future, this method can be used to detect new genetic causes of cancer. Another author adds: "More than 30 such mutation patterns are already described, which are not only specific for NTHL1 defects. If all the tumors in a patient with multiple types of cancer have the same mutation pattern, this is a strong indication that there is a genetic cause. This means that all these tumors developed in the same way.
Gene involved in colorectal cancer also causes breast cancer
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