Genetically related cancers

Key features and cancer risks associated with common hereditary cancer syndromes.

Hereditary cancer syndromes are caused by variants 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 cancers, 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. Genetics 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  Moderately increased risk Occasional distinguishing features (1)

Hereditary Breast and Ovarian Cancer syndrome

BRCA1
BRCA2

Breast
Ovarian

Prostate
Pancreas
Melanoma

 Tumor with triple negative histology (2)

Lynch syndrome

MLH1
MSH2
MSH6
PMS2
EPCAM

Colorectal
Endometrial
Gastric
Small intestine

Liver
Gall bladder
Urinary tract
Brain
Skin
Ovary

Tumor with high MSI (3)
Sebaceous gland tumor 

Familial Adenomatous Polyposis

APC
MUTYH

Colorectal

Gastric
Duodenum
Soft tissue
Bone

10s-100s of adenomatous GI polyps
Dental abnormalities (4)
CHRPE (5) 

Cowden syndrome

PTEN

Breast
Thyroid
Endometrial

Colorectal
Kidney
Melanoma

Head size ≥ 97th percentile
Mucocutaneous lesions
Hamartomatous GI polyps
Autism spectrum disorder

Li-Fraumeni syndrome

TP53

Breast
Bone
Soft tissue

Leukemia
Adrenal
Brain

Very early age at cancer diagnosis (≤ 35 years)
Sarcomas 

(1) These findings are neither pathognomonic nor present in every case
(2) ER-, PR-, HER2-
(3) Microsatellite instability
(4) May include supernumerary teeth, odontoma or other dental anomalies
(5) Congenital hypertrophy of the retinal pigment epithelium