Genetics and Hereditary Cancers

Hereditary Cancer Syndromes

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Hereditary cancer syndromes are diseases caused by gene mutations that can be passed from parent to child, thus increasing the child’s risk of developing cancer.

Certain signs are commonly associated with hereditary cancers, although having these signs does not mean a particular family has a hereditary cancer syndrome. UT Southwestern Medical Center genetic counselors can help families understand the signs of hereditary cancer in their family and look more closely at their family history for additional clues.

Some signs of hereditary cancer in a family are:

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

If one person in a family has already had positive genetic testing, it is important for other relatives to be tested. 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 test 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.

Hereditary Cancer Syndromes and Gene-Associated Cancers

See below for detailed information about specific hereditary cancer syndromes and gene-associated cancers.

APC I1307K Mutation

Gene

APC I1307K

Component Cancers/Tumors

Colon Cancer

Download Fact Sheet

APCI1307K Mutation - English

APCI1307K Mutation - Spanish

Download Clinical Guide

APCI1307K Clinical Guide

ATM-Associated Cancers

Gene

ATM

Component Cancers/Tumors

Breast, pancreatic (heterozygous carriers or one mutation)

Non-Hodgkin lymphoma, leukemia, central nervous system (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 mutations) associated with early-onset ataxia, oculocutaneous telangiectasia, oculomotor apraxia, immunodeficiency

Download Fact Sheet

ATM Fact Sheet - English

ATM Fact Sheet - Spanish

Download Clinical Guide

ATM Clinical Guide

AXIN2-Associated Cancers

Gene

AXIN2

Component Cancers/Tumors

Colon polyps, colorectal cancer

Other Features

Missing teeth, sparse body hair and eyebrows

Download Fact Sheet

AXIN2 Fact Sheet - English

AXIN2 Fact Sheet - Spanish

Download Clinical Guide

AXIN2 Clinical Guide

BAP1-Associated Cancers

Gene

BAP1

Component Cancers/Tumors

Uveal melanoma, malignant mesothelioma, cutaneous melanoma, renal cell carcinoma 

Other Features

Non-cancerous skin lesions

Download Fact Sheet

BAP1 Fact Sheet - English

BAP1 Fact Sheet - Spanish

Download Clinical Guide

BAP1 Clinical Guide

BARD1-Associated Cancers

Gene

BARD1

Component Cancers/Tumors

Breast cancer

Cancer/Tumor Associations with Limited Evidence

Ovarian

Download Fact Sheet

BARD1 Fact Sheet - English

BARD1 Fact Sheet - Spanish

Download Clinical Guide

BARD1 Clinical Guide

Birt Hogg Dubé Syndrome (FLCN mutations)

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)

Download Fact Sheet

FLCN Fact Sheet - English

FLCN Fact Sheet - Spanish

Download Clinical Guide

FLCN Clinical Guide

BRIP1-Associated Cancers

Gene

BRIP1

Component Cancers/Tumors

Ovarian cancer

Cancer/Tumor Associations with Limited Evidence

Breast cancer

Download Fact Sheet

BRIP1 Fact Sheet - English

BRIP1 Fact Sheet - Spanish

Download Clinical Guide

BRIP1 Clinical Guide

CDC73-Associated Cancers

Gene

CDC73

Related Conditions

Familial isolated hyperparathyroidism (FIHP), parathyroid carcinoma, and hyperparathyroidism-jaw tumor (HPT-JT) syndrome

Download Clinical Guide

CDC73 Clinical Guide

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

CHEK2 Fact Sheet - Spanish

Download Clinical Guide

CHEK2 Clinical Guide

Constitutional Mismatch Repair Deficiency (MLH1, MSH2, MSH6, PMS2, EPCAM biallelic mutations)

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

Download Fact Sheets

CMMRD Fact Sheet - English

CMMRD Fact Sheet - Spanish

MLH1 Fact Sheet

MSH2 Fact Sheet

MSH6 Fact Sheet

PMS2 Fact Sheet

EPCAM Fact Sheet

Download Clinical Guides

MLH1 Clinical Guide

MSH2 Clinical Guide

MSH6 Clinical Guide

PMS2 Clinical Guide

EPCAM Clinical Guide

Cowden Syndrome (PTEN mutations)

Gene

PTEN

Component Cancers

Breast, endometrial (uterine), thyroid (follicular and papillary), colon, melanoma, clear cell renal cell carcinomas, Lhermitte-Duclos disease (LDD), gastrointestinal (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 of greater than 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

Download Clinical Guide

PTEN Clinical Guide

DICER1-Associated Cancers

Gene

DICER1

Component Cancers/Tumors

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

Download Fact Sheet

DICER1 Fact Sheet - English

DICER1 Fact Sheet - Spanish

Download Clinical Guide

DICER1 Clinical Guide

Familial Adenomatous Polyposis (APC mutations)

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

Download Clinical Guide

APC Clinical Guide

Familial Atypical Mole and Malignant Melanoma (CDKN2A/CDK4 mutations)

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

CDKN2A Fact Sheet - English

CDKN2A Fact Sheet - Spanish

Download Clinical Guide

CDKN2A Clinical Guide

Fanconia Anemia (FA)

Gene

One of 16 genes

Component Cancers/Tumors

Cancers of the blood, head and neck, skin, gastrointestinal (GI), and gynecologic system 

Other Features

Increased risks of bone marrow failure (aplastic anemia), physical abnormalities

Download Fact Sheet

FA Fact Sheet - English

FA Fact Sheet - Spanish

Gorlin Syndrome/Nevoid Basal Cell Carcinoma Syndrome (PTCH1 and SUFU mutations)

Genew

PTCH, SUFU

Component Cancers/Tumors

Basal cell carcinomas (BCC), meningiomas, primitive neuroectodermal tumor (PNET), 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 (greater than 97th percentile), cleft lip and/or palate, polydactyly (extra digits), eye anomalies (cataracts, coloboma, microphthalmia)

Download Fact Sheet

PTCH1 Fact Sheet - English

PTCH1 Fact Sheet - Spanish

SUFU Fact Sheet - English

SUFU Fact Sheet - Spanish

Download Clinical Guide

PTCH1 Clinical Guide

SUFU Clinical Guide

GREM1-Associated Cancers

Gene

GREM1

Component Cancers/Tumors

Colorectal cancer and polyps

Download Fact Sheet

GREM1 Fact Sheet - English

GREM1 Fact Sheet - Spanish

Hereditary Breast and Ovarian Cancer Syndrome (BRCA1 and BRCA2 mutations)

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

Download Clinical Guide

BRCA Clinical Guide

Hereditary Diffuse Gastric Cancer (CDH1 mutations)

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

Download Clinical Guide

CDH1 Clinical Guide

Hereditary Leiomyomatosis and Renal Cell Cancer (FH mutations)

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 - English

FH Fact Sheet - Spanish

Download Clinical Guide

FH Clinical Guide

Hereditary Leukemia

Gene

More than 20 genes

Component Cancers/Tumors

Leukemia

Download Fact Sheet

Hereditary Leukemia Fact Sheet - English

Hereditary Leukemia Fact Sheet - Spanish

Hereditary Papillary Renal Cell Cancer (MET mutations)

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

Download Fact Sheet

MET Mutations - English

MET Mutations - Spanish

Hereditary Pheochromocytoma/Paraganglioma (SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX mutations)

Gene

SDHA/B/C/D/AF2, MAX

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

SDHx Fact Sheet - English

SDHx Fact Sheet - Spanish

MAX Fact Sheet - English

MAX Fact Sheet - Spanish

Download Clinical Guides

SDHA Clinical Guide

SDHB Clinical Guide

SDHC Clinical Guide

SDHD Clinical Guide

MAX Clinical Guide

Hereditary Retinoblastoma (RB1 mutations)

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 - English

RB1 Fact Sheet - Spanish

Download Clinical Guide

RB1 Clinical Guide

HOXB13-Associated Cancers

Gene

HOXB13

Component Cancers/Tumors

Prostate cancer

Download Clinical Guide

HOXB13 Clinical Guide

Juvenile Polyposis Syndrome (BMPR1A and SMAD4 mutations)

Gene

BMPR1A/SMAD4

Component Cancers/Tumors

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

Download Fact Sheet

Juvenile Polyposis Syndrome Fact Sheet - English

Juvenile Polyposis Syndrome Fact Sheet - Spanish

Download Clinical Guide

Juvenile Polyposis Clinical Guide

KIT-Associated Cancers

Gene

KIT

Conditions 

Piebaldism, gastrointestinal stromal tumors (GISTs), and familial mastocytosis

Download Clinical Guide

KIT Clinical Guide

Li-Fraumeni Syndrome (TP53 mutations)

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

Download Clinical Guide

TP53 Clinical Guide

Lynch Syndrome (MLH1, MSH2, MSH6, PMS2 and EPCAM mutations)

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

MLH1 Fact Sheet - English

MLH1 Fact Sheet - Spanish

MSH2 Fact Sheet - English

MSH2 Fact Sheet - Spanish

MSH6 Fact Sheet - English

MSH6 Fact Sheet - Spanish

PMS2 Fact Sheet - English

PMS2 Fact Sheet - Spanish

EPCAM Fact Sheet - English

EPCAM Fact Sheet - Spanish

Download Clinical Guides

MLH1 Clinical Guide

MSH2 Clinical Guide

MSH6 Clinical Guide

PMS2 Clinical Guide

EPCAM Clinical Guide

MC1R-Associated Cancers

Gene

MC1R

Component Cancers

Skin cancer

Download Clinical Guide

MC1R Clinical Guide

MRE11A-Associated Cancers

Gene

MRE11A

Component Cancers/Tumors

None

Cancers/Tumor Associations with Limited Evidence

Breast and ovarian cancers

Download Clinical Guide

MRE11A Clinical Guide

MSH3-Associated Cancers

Gene

MSH3

Component Cancers/Tumors

Adenomatous polyps in the colon and small intestine, as well as colorectal and stomach cancers 

Cancers/Tumor Associations with Limited Evidence

Brain tumors

Download Fact Sheet

MSH3 Fact Sheet - English

MSH3 Fact Sheet - Spanish

Download Clinical Guide

MSH3 Clinical Guide

Multiple Endocrine Neoplasia Type 1 (MEN1 mutations)

Gene

MEN1

Component Cancers/Tumors

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

Other features

Facial angiofibromas, collagenomas, lipomas

Download Fact Sheet

MEN1 Fact Sheet - English

MEN1 Fact Sheet - Spanish

Download Clinical Guide

MEN1 Clinical Guide

Multiple Endocrine Neoplasia Type 2 (RET mutations)

Gene

RET

Component Cancers/Tumors

Medullary thyroid cancer, pheochromocytoma, parathyroid neoplasia, adrenal tumors

Download Fact Sheet

MEN2 Fact Sheet - English

MEN2 Fact Sheet - Spanish

Download Clinical Guides

MEN2 High Risk Clinical Guide

MEN2 Moderate Risk Clinical Guide

MUTYH-Associated Cancers

Gene

MUTYH

Component Cancers/Tumors

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

Other features

Extra/impacted teeth, congenital retinal pigment epithelial hypertrophy (CHRPE)

Download Fact Sheets

MUTYH Mutations - English 

MUTYH Fact Sheet - Spanish

Download Clinical Guides

MUTYH Clinical Guide

MUTYH-Associated Polyposis (MAP) Clinical Guide

NBN-Associated Cancers

Gene

NBN

Component Cancers/Tumors

Breast cancer

Cancer/Tumor Associations with Limited Evidence

Ovarian, prostate, and skin cancers

Download Fact Sheet

NBN Fact Sheet - English

NBN Fact Sheet - Spanish

Download Clinical Guide

NBN Clinical Guide

Neurofibromatosis Type 1 (NF1 mutations)

Gene

NF1

Component Cancers/Tumors

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

Download Fact Sheet

NF1 Fact Sheet- English

NF1 Fact Sheet - Spanish

Download Clinical Guide

NF1 Clinical Guide

NTHL1-Associated Cancers

Gene

NTHL1

Component Cancers/Tumors

Colorectal polyps, which can become cancerous if untreated

Download Fact Sheet

NTHL1 Fact Sheet - English

NTHL1 Fact Sheet - Spanish

Download Clinical Guide

NTHL1 Clinical Guide

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

PALB2 Fact Sheet - Spanish

Download Clinical Guide

PALB2 Clinical Guide

Peutz-Jeghers Syndrome (STK11 mutations)

Gene

STK11

Component Cancers/Tumors

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

Other features

Pigmented macules on skin and mouth

Download Fact Sheet

STK11 Fact Sheet - English

STK11 Fact Sheet - Spanish

Download Clinical Guide

STK11 Clinical Guide

POLD1-Associated Cancers

Gene

POLD1

Component Cancers/Tumors

Colorectal cancer and adenomas

Cancer/Tumor Associations with Limited Evidence

Endometrial and other extra-intestinal cancers

Download Fact Sheet

POLD1 Fact Sheet - English

POLD1 Fact Sheet - Spanish

Download Clinical Guide

POLD1 Clinical Guide

POLE-Associated Cancers

Gene

POLE

Component Cancers/Tumors

Colorectal cancer and adenomas

Cancer/Tumor Associations with Limited Evidence

Extra-intestinal cancers

Download Fact Sheet

POLE Fact Sheet - English

POLE Fact Sheet - Spanish

RAD50-Associated Cancers

Gene

RAD50

Component Cancers/Tumors

None

Cancer/Tumor Associations with Limited Evidence

Breast and ovarian cancers

Download Fact Sheet

RAD50 Fact Sheet - English

RAD50 Fact Sheet - Spanish

Download Clinical Guide

RAD50 Clinical Guide

RAD51C-Associated Cancers

Gene

RAD51C

Component Cancers/Tumors

Ovarian cancer 

Cancer/Tumor Associations with Limited Evidence

Breast cancer

Download Fact Sheet

RAD51C Fact Sheet - English

RAD51C Fact Sheet - Spanish

Download Clinical Guide

RAD51C Clinical Guide

RAD51D-Associated Cancers

Gene

RAD51D

Component Cancers/Tumors

Ovarian cancer

Cancers/Tumors Associations with Limited Evidence

Breast cancer

Download Fact Sheet

RAD51D Fact Sheet - English

RAD51D Fact Sheet - Spanish

Download Clinical Guide

RAD51D Clinical Guide

Rhabdoid Tumor Predisposition Type 2 (SMARCA4 mutations)

Gene

SMARCA4

Component Cancers/Tumors

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

Download Fact Sheet

SMARCA4 Fact Sheet - English

SMARCA4 Fact Sheet - Spanish

Tuberous Sclerosis (TSC1 and TSC2 mutations)

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

Download Fact Sheet

Tuberous Sclerosis Fact Sheet - English

Tuberous Sclerosis Fact Sheet - Spanish

Download Clinical Guide

Tuberous Sclerosis Clinical Guide

Von Hippel-Lindau (VHL mutations)

Gene

VHL

Component Cancers/Tumors

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

Download Fact Sheet

Von-Hippel Lindau Fact Sheet

VHL Fact Sheet - English

VHL Fact Sheet - Spanish

Download Clinical Guide

VHL Clinical Guide