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 risk1 | Moderately increased risk1 | Occasional distinguishing features2 |
Hereditary breast and ovarian cancer syndrome | BRCA1 | Breast | Male breast | Breast tumor with triple negative histology3 |
Lynch syndrome | MLH1 | Colorectal
| Gastric | Tumor with absent MMR protein or high MSI4 Sebaceous gland tumors Keratoacanthomas |
Familial adenomatous polyposis syndrome | APC | Colorectal | Duodenal | 10s-100s of adenomatous GI polyps Dental abnormalities5 CHRPE6 |
| MUTYH-associated adenomatous polyposis syndrome | MUTYH | Colorectal | Duodenal | 10s-100s of adenomatous GI polyps, may see polyps of other histologies. Autosomal recessive inheritance; heterozygotes at moderate risk of CRC |
Cowden syndrome | PTEN | Breast | Colorectal | Head size ≥ 97th percentile (58cm women, 60cm men) Mucocutaneous lesions Lipomas Hamartomatous GI polyps Autism spectrum disorder Intellectual disability (IQ≤75) Arteriovenous malformation Bannayan-Riley-Ruvalcaba syndrome Proteus syndrome Lhermitte-Duclos disease |
Li-Fraumeni syndrome | TP53 | Breast | Lung | Very early age at cancer diagnosis (≤ 35 years) Very high lifetime risk for cancer |
Familial multiple mole and melanoma syndrome | CDKN2A, CDK4 | Melanoma | Pancreatic | Multiple skin moles |
Peutz Jeghers syndrome | STK11 | Breast | Testicular | Hyperpigmented mucocutaneous lesions PJS-type hamartomatous GI polyps Sex cord tumors (SCTAT) of ovaries Sertoli cell tumors (LCST) of testes |
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) Arteriovenous malformation (HHT) |
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
Reviewed November 2021