APC: Gene Mutations and Cancer Risks
Cancer Risks in People with an Inherited Mutation
Experts at the National Comprehensive Cancer Network (NCCN) created guidelines which estimate the cancer risks for people with mutations. These cancer risk estimates are updated based on the latest research.
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 mutation, I1307K. See below for the specific cancer risks in people with that variant.
|
Cancer Type |
Estimated Lifetime Risk (to Age 80) with FAP or AFAP |
Average Lifetime Risk for General Population |
Average Age of Onset with FAP |
|
Colon cancer without colectomy |
|
4% |
39 years (median) |
|
Rectal/pouch cancer after colectomy |
|
4% |
|
|
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 v. 1, 2025. |
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mutation I1307K
People with a mutation called I1307K in the gene do not develop FAP. Unlike people with FAP, people with this mutation have only a slightly elevated risk for colorectal cancer above the general population. The lifetime risk for colorectal cancer with this mutation is estimated to be about 5-10% and the mutation is not known to increase risk for other cancers.