FANCC heterozygote: (one copy of a FANCC mutation)
There is preliminary evidence suggesting pathogenic variants in FANCC may be associated with a predisposition to breast and pancreatic cancer. There may also be an increased risk for other cancer types, but the evidence is currently limited. FANCC is therefore considered to be a preliminary evidence gene for autosomal dominant cancer. This uncertainty may be resolved as new information becomes available, which is the reason that clinicians continue to order these preliminary evidence genes.
The FANCC gene is one of a group of classical Fanconi anemia genes whose protein products physically interact in a multiprotein core complex. FANCC encodes a DNA-repair protein that may operate in a postreplication repair or a cell-cycle checkpoint function. This protein may be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. If there is a pathogenic variant in this gene that prevents it from functioning normally, the risk of developing certain types of cancers is increased.
Individuals with a single pathogenic variant (mutation) in FANCC are also carriers of Fanconi anemia type C. Fanconi anemia is an autosomal recessive disorder that is characterized by bone marrow failure and variable presentation of additional anomalies, including short stature, abnormal skin pigmentation, abnormal thumbs, malformations of the skeletal and central nervous systems, and developmental delay. Risks for leukemia and early onset solid tumors are significantly elevated. For there to be a risk of Fanconi anemia in offspring, a person and and his or her partner would both have to have a single pathogenic variant in FANCC; in such a case, the risk of having an affected child is 25%.
Because the evidence regarding FANCC and breast and pancreatic cancer risk is limited and preliminary, there are no guidelines or recommendations at this time to suggest alterations to medical management based solely on the presence of a pathogenic FANCC variant. However, an individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.