Genetically Related Cancers
Key features and cancer risks associated with common hereditary cancer syndromes.
Hereditary cancer syndromes are caused by variants (mutations) in genes that control cell growth in multiple tissue types. These variants often cause differences in gene expression within specific tissues. Recognizing genetically related cancers is important not only for identifying families that are suspicious for hereditary syndromes, but also for thinking ahead about how results will be used. In addition, some hereditary cancer syndromes involve distinctive tumor histology or physical features. Recognizing these findings can alert you to the need to analyze a different or additional cancer risk gene. Genetic experts can help identify the best testing strategy.
As more people have genetic testing, and the number of genes being analyzed for each patient expands, our understanding of associated cancer risks has changed. The table below includes the cancers and features most commonly associated with the particular syndrome, but is not exhaustive. In addition, some individuals and families have an atypical history.
| Name | Most common genes | Significantly increased risk (1) | Moderately increased risk (1) | Occasional distinguishing features (2) |
|
Hereditary breast and ovarian cancer syndrome |
BRCA1 |
Breast |
Male breast |
Breast tumor with triple negative histology (3) |
|
Lynch syndrome |
MLH1 |
Colorectal
|
Gastric |
Tumor with absent MMR protein or high MSI (4) |
|
Familial adenomatous polyposis syndrome |
APC |
Colorectal |
Duodenal Periampullary Thyroid Medulloblastoma Epidermoid cysts |
10s-100s of adenomatous GI polyps |
| MUTYH-associated adenomatous polyposis syndrome | MUTYH | Colorectal |
Duodenal |
10s-100s of adenomatous GI polyps, may see polyps of other histologies. |
|
Cowden syndrome |
PTEN |
Breast Kidney |
Colorectal |
Head size ≥ 97th percentile (58cm women, 60cm men) |
|
Li-Fraumeni syndrome |
TP53 |
Breast |
Lung |
Very early age at cancer diagnosis (≤ 35 years) |
|
Familial multiple mole and melanoma syndrome |
CDKN2A, CDK4 |
Melanoma |
Pancreatic |
Multiple skin moles |
|
Peutz Jeghers syndrome |
STK11 |
Breast |
Testicular |
Hyperpigmented mucocutaneous lesions |
|
Hereditary diffuse gastric cancer |
CDH1 |
Breast, lobular pathology |
Colorectal |
n/a |
|
Juvenile polyposis syndrome |
BMPR1A, SMAD4 |
Gastric |
Small bowel |
GI tract polyps (Juvenile polyp histology) |
(1) Cancer risks may vary based on gene associated with syndrome
(2) These findings are neither pathognomonic nor present in every case
(3) ER-, PR-, HER2-
(4) Microsatellite instability
(5) May include supernumerary teeth, odontoma or other dental anomalies
(6) Congenital hypertrophy of the retinal pigment epithelium
See National Comprehensive Cancer Network (NCCN) guidelines for more detailed information about these genes and others that can be included on multigene panels.
Updated August 2023