ICARE Newsletter Winter 2017

A Newly Identified Inherited Colon Cancer Gene: FAN1

There continues to be rapid advances in identifying new genes involved in inherited cancer risk.  An example of yet another recently identified gene is FAN1, in which a nonsense variant (i.e. the premature change or loss of a protein) was identified following exome sequencing in 3 individuals from a family who met clinical criteria for Lynch syndrome yet did not have any mutations identified in Lynch genes and had mismatch-proficient tumors. The FAN1 gene is involved in the Fanconi anemia DNA repair pathway, but is not known to be a gene involved in Fanconi anemia (a condition which can cause bone marrow failure). Study investigators subsequently tested an additional 176 families with family histories of colorectal cancer and identified FAN1 mutations in ~3%, of which all met clinical criteria for Lynch syndrome and also had mismatch proficient tumors.  These findings suggest that mutations in the FAN1 gene may lead to inherited susceptibility to colorectal cancer.  Additional studies are needed to determine the proportion of inherited colorectal cancer that may be due to mutations in this gene, as well as the level of risk incurred by mutations in this gene.

SeguĂ­ N,et al. Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair. Gastroenterology. 2015 Jun 4. PMID: 26052075.

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