APC: Gene Mutations and Cancer Risks
Cancer Risks in People with an Inherited APC Mutation
Familial adenomatous polyposis (FAP) and attenuated familial adenomatous
polyposis (AFAP)
Without surgery, almost all people with FAP will develop colorectal cancer in their lifetime, often before age 40. The estimated lifetime cancer risks for people with FAP are listed below. People with the attenuated form of FAP (AFAP) may have lower lifetime risks for cancer, and the degree of risk depends on the severity of their polyp history. Importantly, these risks do not apply to people who have the specific APC variant I1307K. See below for the specific cancer risks in people with that variant.
Cancer Type |
Estimated Lifetime Risk (to Age 80) with an FAP Mutation |
Average Lifetime Risk for General Population |
Average Age of Onset with FAP |
Colon cancer without colectomy |
Close to 100% |
4.1% |
39 years (median) |
Rectal/pouch cancer after colectomy |
|
|
|
Duodenum or periampullary cancer |
<1-10% |
50-52 years |
|
Gastric |
0.1-7.1% |
0.8% |
52-57 years |
Small bowel cancer (beyond the duodenum) |
<1% |
0.3% |
43 years |
Thyroid (mostly papillary thyroid carcinoma) |
1.2-12% |
1.2% |
26-44 years |
Intra-abdominal desmoid tumors |
10 - 24% (more common with mutations at the 3' end of the gene) |
Rare |
|
Brain/CNS (mostly medulloblastoma) |
1% |
0.6% |
18 years |
Hepatoblastoma |
0.4-2.5% (usually before age 5) |
Very rare |
18-33 months |
Source: NCCN Guidelines: Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric vs. 1 2024 |
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APC variant I1307K
People with an I1307K variant in the APC gene do not develop FAP. Unlike people with FAP, people with the APC variant I1307K have only a slightly elevated risk for colorectal cancer above the general population. The lifetime risk for colorectal cancer with this variant is estimated to be about 5-10%. The I1307K variant is not known to increase risk for other cancers. |