Link Between Fanconi Anemia Genetic Mutations and Cancer Risk

October 23, 2017

Researchers have discovered that genetic mutations associated with Fanconi Anemia may also result in a higher risk for certain cancers, even in patients who don't exhibit symptoms of the disease.

Spanish and French researchers have recently found that mutations in the gene associated with Fanconi anemia may predispose individuals to certain cancers and sensitivity to cancer treatments, even if they did not exhibit classical signs of Fanconi anemia. This discovery was published recently in the journal Genetics in Medicine.

Fanconi anemia is a genetic condition affecting the bone marrow and other body systems, and occurs in approximately 1 in 160,000 individuals throughout the world. The disease is most common in individuals of certain ethnicities such as Ashkenazi Jews, Spanish Roma, and Black South Africans.

Fanconi anemia is an inherited condition caused by genetic mutations in one of at least 15 genes, with 80% to 90% of Fanconi anemia cases due to mutations in the FANCA, FANCC, or FANCG genes. Due to these genetic mutations, damaged DNA is unable to undergo proper repair and can have negative consequences for rapidly dividing cells, such as those in the bone marrow and fetal cells, which can cause abnormalities that include absence of kidneys and genitalia, skeletal defects, and other vital organ defects. Unfortunately, this can also lead to an increased susceptibility to certain cancers-such as myeloid leukemia and breast cancer-and cancer-related treatment toxicity.

In the study led by Massimo Bogliolo of the Instituto de Salud Carlos III in Madrid, Spain, and colleagues found that the three study subjects who had biallelic FANCM truncating mutations and underwent genomic sequencing were noted not to harbor signs of Fanconi anemia; however, they were also found to be susceptible to developing early-onset cancers (including leukemia and head and neck cancer) and a higher risk for toxicity from chemotherapy.

Additionally it was reported in the same issue of Genetics in Medicine that patients with a biallelic FANCM mutation but without typical Fanconi Anemia symptoms also had a higher risk for breast cancer susceptibility, early onset menopause, and the potential for chromosomal fragility.

Based on these data, genetic mutation screening for cancer may be warranted in certain populations, and those with FANCM mutations may require additional monitoring when receiving cancer treatments such as chemotherapy and/or radiation therapy.