Hereditary Cancer Syndromes

The “signs” listed below are commonly associated with hereditary cancers, though having these signs does not mean your family has a hereditary cancer syndrome. Looking at family history can give us more clues.

Signs of hereditary cancer in a family include:

  • Cancer is diagnosed at an unusually young age
  • There is the same type of cancer in multiple close relatives
  • You or a family member are of Ashkenazi Jewish ancestry (Eastern or Central European descent) and have either breast or ovarian cancer
  • You or a family member have a rare cancer/tumor such as a sarcoma, male breast cancer, medullary thyroid cancer, or a pheochromocytoma
  • You have a family history with a combination of breast and ovarian cancers or colon and uterine cancers
  • You have more than 20 colon polyps
  • You or a family member have had multiple kinds of cancer

If someone in your family has already had positive genetic testing, it is important for other relatives to have testing. Usually, single-site testing (to look only for the mutation already identified in a relative) is performed to see if other relatives have inherited the same mutation. This will clarify the cancer risks for other relatives and determine if more screening or risk-reducing surgery should be considered. However, it is important to do a complete risk assessment to rule out the need for genetic testing beyond the known mutation.

For detailed information about specific hereditary cancer syndromes and gene-associated cancers, choose from the menu below.

ATM Associated Cancers

Gene

ATM

Component Cancers/Tumors

Breast, pancreatic (heterozygous carriers or one mutation)

Non-Hodgkin lymphoma, leukemia, CNS cancers, gastric cancer, uterine cancer, basal cell carcinoma (BCC), ovarian dysgerminomas (autosomal recessive Ataxia Telangiectasia)

Cancer/Tumor Associations with Limited Evidence

Prostate (heterozygous carriers or one mutation)

Other Features

Ataxia Telangiectasia (autosomal recessive or two mutation) associated with early-onset ataxia, oculocutaneous telangiectasies, oculomotor apraxia, immunodeficiency

BARD1 Associated Cancers

Gene

BARD1

Component Cancers/Tumors

Breast cancer

Cancer/Tumor Associations with Limited Evidence

Ovarian

Birt-Hogg-Dube Syndrome

Gene

FLCN

Component Cancers/Tumors

Renal cell carcinomas (chromophobe, clear cell, papillary), renal tumors (oncocytomas, oncocytic hybrid tumors)

Cancer/Tumor Associations with Limited Evidence

Lipomas, collagenomas, colon polyps

Other Features

Primary spontaneous pneumothorax, pulmonary cysts, skin manifestations (perifollicular fibromas, fibrofolliculomas, trichodiscomas, acrochordons)

BRIP1 Associated Cancers

Gene

BRIP1

Component Cancers/Tumors

Ovarian cancer

Cancer/Tumor Associations with Limited Evidence

Breast cancer

CHEK2 Associated Cancers

Gene

CHEK2

Component Cancers/Tumors

Breast (bilateral), colon, and prostate

Cancer/Tumor Associations with Limited Evidence

Ovarian, thyroid, and renal cancers

Download Fact Sheet

CHEK2 Fact Sheet - English

Constitutional Mismatch Repair Deficiency

Gene

MLH1/MSH2/MSH6/PMS2/EPCAM (biallelic mutations or two mutations in the same gene)

Component Cancers

Colon, stomach, small intestine, leukemia, lymphoma, and brain tumors.

Other Features

Café au lait spots

Cowden Syndrome

Gene

PTEN

Component Cancers

Breast, endometrial (uterine), thyroid (follicular and papillary), colon, melanoma, clear cell renal cell carcinomas, Lhermitte-Duclos disease (LDD), GI hamartomas, lipomas, fibromas, thyroid adenomas and goiters

Other Features

Skin findings (trichilemmomas, cutaneous and/or oral mucosal papillomatosis, acral keratoses, palmoplantar keratoses), macrocephaly (large head circumference: >97th percentile), intellectual disability (IQ of 75 or under), fibrocystic breast disease, uterine fibroids

Download Fact Sheet

PTEN Fact Sheet - English

PTEN Fact Sheet - Spanish

DICER1 Associated Cancers

Gene

DICER1

Component Cancers/Tumors

Pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian Sertoli-Leydig cell tumors (SCLTs)

Familial Adenomatous Polyposis

Gene

APC

Component Cancers/Tumors

Colorectal, small bowel (ampulla of Vater), gastric, pancreatic, bile duct, non-medullary thyroid, hepatoblastoma, and CNS tumors, adenomatous polyps of the GI tract, fundic gland polyps in the stomach, desmoid tumors, jaw osteomas, adrenal adenomas, lipomas, juvenile nasopharangeal angiofibromas

Other Features

Congenital hypertrophe of the retinal pigment epithelium (CHRPE), supernumerary or absent teeth, dentigerous cysts, sebaceous or epidermoid cysts

Download Fact Sheets

APC Fact Sheet - English

APC Fact Sheet - Spanish

Familial Atypical Mole and Malignant Melanoma

Gene

CDKN2A (p16)/CDK4

Component Cancers/Tumors

Melanoma, dysplastic nevi, pancreatic cancer, astrocytoma

Cancer/Tumor Associations with Limited evidence

Breast cancer, head and neck squamous cell carcinomas (SCC)

Download Fact Sheet

CDKN2 Fact Sheet

Gorlin Syndrome/NBCCS

Gene

PTCH

Component Cancers/Tumors

Basal cell carcinomas (BCC), meningiomas, primitive neuroectodermal tumor (PNETs), jaw keratocysts, sebaceous and dermoid cysts, cardiac fibromas, fetal rhabdomyomas, ovarian fibromas

Cancer/Tumor Associations with Limited Evidence

Ovarian fibrosarcomas

Other Features

Ectopic calcification of the falx cerebri, palmar/plantar pits, congenital skeletal anomalies, larger head circumference (>97th percentile), cleft lip and/or palate, polydactyly (extra digits), eye anomalies (cataracts, coloboma, microphthalmia)

Download Fact Sheet

PTCH Fact Sheet

GREM1 Associated Cancers

Gene

GREM1

Component Cancers/Tumors

Colorectal cancer and polyps

Hereditary Breast and Ovarian Cancer

Gene

BRCA1/BRCA2

Component Cancers/Tumors

Breast, ovarian, prostate, male breast, pancreatic, melanoma

Cancers/Tumors Associations with Limited Evidence

Colon, gastric, gallbladder, bile duct, and endometrial

Download Fact Sheets

BRCA Fact Sheet - English

BRCA Fact Sheet - Spanish

Hereditary Diffuse Gastric Cancer

Gene

CDH1

Component Cancers/Tumors

Diffuse gastric cancer, lobular breast cancer

Cancers/Tumors Associations with Limited Evidence

Ductal breast cancer, signet ring colon cancer, islet cell pancreatic cancer

Download Fact Sheets

CDH1 Fact Sheet - English

CDH1 Fact Sheet - Spanish

Hereditary Leiomyomatosis and Renal Cell Cancer

Gene

FH

Component Cancers/Tumors

Renal Cell Carcinoma (type II papillary), uterine leiomyosarcoma, uterine and cutaneous leiomyomata

Cancer/Tumor Associations with Limited Evidence

Testicular Leydig cell tumors, adrenal adenomas, ovarian cystadenomas

Download Fact Sheet

FH Fact Sheet

Hereditary Papillary Renal Cancer

Gene

MET

Component Cancers/Tumors

Renal Cell Carcinoma (type I papillary), papillary renal adenomas

Cancer/Tumor Associations with Limited Evidence

Carcinomas of the lung, pancreas, stomach, rectum, and bile duct

Hereditary Pheochromocytoma/PGL

Gene

SDHA/B/C/D/AF2

Component Cancers/Tumors

Pheochromocytoma (PCC), Paraganglioma (PGL), Renal Cell Carcinoma (RCC), Gastrointestinal Stromal Tumors (GIST)

Cancer/Tumor Associations with Limited Evidence

Non-medullary thyroid cancers, other neuroendocrine tumors

Download Fact Sheet

SDH Fact Sheet

Hereditary Retinoblastoma

Gene

RB1

Component Cancers/Tumors

Retinoblastoma, pineoblastoma, sarcoma (osteosarcoma, chondrosarcoma, fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma), melanoma

Cancer/Tumor Associations with Limited Evidence

Leukemia, lymphoma, brain tumors, sebaceous carcinomas of the eyelid, malignant phyllodes tumors, retinomas, lipomas

Download Fact Sheet

RB1 Fact Sheet

Juvenile Polyposis

Gene

BMPR1A/SMAD4

Component Cancers/Tumors

GI juvenile-type hamartomatous polyps (stomach, small intestine, colon, and rectum); colon, stomach, upper GI, and pancreatic cancers

Li-Fraumeni

Gene

TP53

Component Cancers/Tumors

Early-onset breast cancer, sarcomas, brain tumors, adrenal cortical carcinoma leukemia

Cancers/Tumor Associations with Limited Evidence

Renal cell cancer, lymphoma

Download Fact Sheets

TP53 Fact Sheet - English

TP53 Fact Sheet - Spanish

Lynch Syndrome

Gene

MLH1, MSH2, MSH6, PMS2, EPCAM

Component Cancers

Colorectal, uterine, ovarian, gastric, small bowel, pancreatic, CNS tumors, bladder/ureter cancer, hepatobiliary, and renal cancers

Cancers/Tumor Associations with Limited Evidence

Breast cancer

Download Fact Sheets

Lynch Fact Sheet - English

Lynch Fact Sheet - Spanish

MRE11A Associated Cancers

Gene

MRE11A

Component Cancers/Tumors

None

Cancers/Tumor Associations with Limited Evidence

Breast and ovarian cancers

Multiple Endocrine Neoplasia Type 1

Gene

MEN1

Component Cancers/Tumors

Parathyroid, pituitary tumor, pheos, pancreatic tumors (insulinomas, gastrinomas, VIPomas), carcinoids, adrenocortical cancers

Other features

Facial angiofibromas, collagenomas, lipomas

Download Fact Sheet

MEN1 Fact Sheet

Multiple Endocrine Neoplasia Type 2

Gene

RET

Component Cancers/Tumors

Medullary thyroid cancer, pheo, parathyroid neoplasia, adrenal tumors

Download Fact Sheet

MEN2 Fact Sheet

MYH Associated Polyposis Syndrome

Gene

MUTYH

Component Cancers/Tumors

Colon polyps; colorectal, small bowel, and gastric cancers; CHRPE (retinal pigmentation), osteomas (benign bone tumor) of the jaw, benign tumors of hair follicles

Other features

Extra/impacted teeth

Download Fact Sheets

MYH Fact Sheet - English

MYH Fact Sheet - Spanish

NBN Associated Cancers

Gene

NBN

Component Cancers/Tumors

Breast cancer

Cancer/Tumor Associations with Limited Evidence

Ovarian, prostate and skin cancers

Neurofibromatosis Type 1

Gene

NF1

Component Cancers/Tumors

Neurofibromas, breast cancer, gliomas, malignant peripheral nerve sheath tumors, pheochromocytoma, leukemia, GIST, and rhabdomyosarcoma

PALB2 Associated Cancers

Gene

PALB2

Component Cancers/Tumors

Breast and pancreatic cancers

Cancer/Tumor Associations with Limited Evidence

Ovarian and male breast cancers

Download Fact Sheet

PALB2 Fact Sheet - English

Peutz-Jeghers Syndrome

Gene

STK11

Component Cancers/Tumors

Gastrointestinal polyps; small bowel, colon, stomach, pancreatic, breast, cervical cancers; ovarian sex cord tumors (SCTATs), and sertoli cell tumors

Other features

Pigmented macules on skin and mouth

POLD1 Associated Cancers

Gene

POLD1

Component Cancers/Tumors

Colorectal cancer and adenomas

Cancer/Tumor Associations with Limited Evidence

Endometrial and other extra-intestinal cancers

POLE Associated Cancers

Gene

POLE

Component Cancers/Tumors

Colorectal cancer and adenomas

Cancer/Tumor Associations with Limited Evidence

Extra-intestinal cancers

RAD50 Associated Cancers

Gene

RAD50

Component Cancers/Tumors

None

Cancer/Tumor Associations with Limited Evidence

Breast and ovarian cancers

RAD51C Associated Cancers

Gene

RAD51C

Component Cancers/Tumors

Ovarian cancer

Cancer/Tumor Associations with Limited Evidence

Breast cancer

RAD51D Associated Cancers

Gene

RAD51D

Component Cancers/Tumors

Ovarian cancer

Cancers/Tumors Associations with Limited Evidence

Breast cancer

Rhabdoid Tumor Predisposition Type 2

Gene

SMARCA4

Component Cancers/Tumors

Atypical teratoid/rhabdoid tumors (AT/RT); malignant rhabdoid tumors of kidney; small cell carcinoma of the ovary, hypercalcemic type (SCCOHT)

Tuberous Sclerosis

Gene

TSC1/TSC2

Component Cancers/Tumors

Benign hamartomas in multiple organs (skin, CNS, kidney, liver, lungs, heart), renal cancer

Other features

Hypopigmented macules, facial angiofibromas, subependymal nodules, cortical and subcortical tubers, seizures, development delay/intellectual disability, renal angiomyolipomas, cardiac rhabdomyomas

Von Hippel-Lindau

Gene

VHL

Component Cancers/Tumors

CNS/retinal hemangioblastomas, renal cancer, pheo, pancreatic/liver cysts and tumors, benign tumors in the ear, cystadenomas of the epididymis (males)

Download Fact Sheet

Von-Hippel Lindau Fact Sheet