Hereditary Cancer Syndromes

What You Should Know About the Low/Moderate Penetrance APC Variant I1307K (c.3920T>A)

Most pathogenic/likely pathogenic (P/LP) variants in the APC gene are associated with a severe genetic condition known as familial adenomatous polyposis syndrome or FAP. Individuals with FAP develop 100s to 1,000s of colon polyps in their lifetime and have almost a 100% risk of developing colon cancer without intervention. However, the I1307K APC variant (c.3920T>A) does not cause FAP. This variant is found in approximately 6-7% of the Ashkenazi Jewish population in the United States and moderately increases the risk of colorectal cancer.

UTSW’s hereditary cancer program is one of the largest in the nation, and we have extensive experience supporting individuals with the I1307K APC variant.

Cancer Risks Associated with the I1307K APC Variant

The risk for colorectal cancer in individuals with the I1307K APC variant is 5-10%. This is compared to the general population’s lifetime risk of 4.1% for developing colorectal cancer.

Managing Cancer Risks

Individuals with the I1307K APC variant should talk to their health care team about an appropriate cancer surveillance plan.

Colon Cancer

• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Colonoscopy every five years starting at age 40
  • Possibly modifying the frequency or starting age if there is colon cancer in the family

Risks to Family Members

The I1307K APC variant is inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with this variant have a 1 in 2 (or 50%) chance of having the variant as well. Both males and females can inherit the variant, and both males and females can pass it on to their children.

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the ATM gene have an increased risk for cancers of the breast, ovary, pancreas, and colon. Females have up to a 25% lifetime risk for breast cancer and up to a 5% lifetime risk for ovarian cancer. Males and females with the variant have up to a 10% risk for pancreatic cancer and a 10% risk for colorectal cancer.

What You Should Know About AXIN2 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the AXIN2 gene have an increased risk for colon cancer.

UTSW is home to one of the largest hereditary cancer programs in the country, with specialized expertise in the clinical management of patients carrying P/LP variants of the AXIN2 gene.

Cancer Risks Associated with an AXIN2 P/LP Variant

Individuals with an AXIN2 P/LP variant have an increased risk of colon adenomas, polyps, and colon cancer. The lifetime risk for colon cancer is unknown. Individuals with the variant may also have permanent teeth that are missing (oligodontia) and sparse eyebrows, scalp, and body hair.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Colon Cancer

• Gastroenterologists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Colonoscopy starting at age 25-30
  • Repeat colonoscopy every one to three years depending on the number of polyps found

Risks to Family Members

P/LP variants in the AXIN2 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an AXIN2 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial AXIN2 P/LP variant, and both males and females can pass it on to their children.

What You Should Know About BAP1 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the BAP1 gene have an increased risk for developing cancers of the kidney, skin, eyes, and lungs over their lifetime.

With one of the largest hereditary cancer programs in the country, UT Southwestern offers tailored care for individuals with BAP1 P/LP variants.

Cancer Risks Associated with a BAP1 Mutation

Approximately 10% of individuals with a BAP1 P/LP variant have kidney cancer. Individuals with the variant also have an increased risk for developing melanoma of the skin (cutaneous) or eyes (uveal) and may develop another skin finding called a BAP1-inactivated melanocytic tumor (BIMT), which has a low risk of turning into cancer. A form of lung cancer called malignant mesothelioma has also been observed in individuals with a BAP1 P/LP variant.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Skin Cancers

• Dermatologists at UT Southwestern work with patients to determine an appropriate skin cancer surveillance plan.
  • This plan often includes a full-body skin exam.

Uveal Melanoma

• Ophthalmologists at UT Southwestern work with patients to establish a surveillance plan for uveal melanoma.
• This surveillance often includes a dilated eye exam and baseline imaging.

Kidney Cancer

• Urology specialists work with patients to determine appropriate surveillance and risk management for hereditary kidney cancer.
• Our specialists follow established surveillance guidelines, including:
  • Abdominal MRI or CT every two years

Risks to family Members

P/LP variants in the BAP1 gene are inherited in an autosomal dominant fashion. This means that parents, brothers, sisters, and children of individuals with a BAP1 P/LP variant have a 1 in 2 or 50% chance of having the same variant.

What You Should Know About BARD1 Pathogenic/Likely Pathogenic Variants

Females with a BARD1 pathogenic/likely pathogenic (P/LP) variant have increased risks for developing cancers of the breast.

UT Southwestern is home to one of the nation’s largest hereditary cancer programs, and we provide expert care for patients with P/LP BARD1 variants.

Cancer Risks Associated with a BARD1 Mutation

Females with a P/LP variant in the BARD1 gene have up to a 30% risk of developing breast cancer over their lifetime.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Breast Cancer

• Breast specialists at UT Southwestern work with patients to determine individual screening and surgical management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Annual mammogram and breast MRI

Risks to family Members

P/LP variants in the BARD1 gene are inherited in an autosomal dominant fashion. This means that parents, brothers, sisters, and children of individuals with a BARD1 P/LP variant have a 1 in 2 or 50% chance of having the same variant.

What You Should Know About FLCN Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the FLCN gene have Birt-Hogg-Dube syndrome (BHD), which increases the risk for skin lesions, lung cysts, and pneumothorax (collapsed lung). Individuals also have an increased risk for kidney cancer.

UTSW is recognized as a VHL Alliance Clinical Care Center (CCC). This designation emphasizes our commitment to providing outstanding, coordinated care for individuals with hereditary kidney cancer syndromes, including BHD.

Cancer Risks Associated with an FLCN P/LP Variant

Individuals with an FLCN P/LP variant have an increased risk for tumors of the kidney, including kidney cancer; 20-35% of people with the variant develop a kidney tumor. These tumors can be benign or cancerous.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Kidney Cancer

• Our kidney specialists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Abdominal/pelvic CT scan with contrast, MRI, or renal ultrasound starting at age 20
  • Repeat every one to three years based on findings

Other Features

• Specialists in dermatology, pulmonology, and other disciplines may also be an important part of the care team.
• Additional surveillance or management recommendations might include:
  • Full skin exam
  • High-resolution computer tomography (HRCT) or CT of the chest
• Lifestyle modifications should be considered, including avoiding cigarette smoking, high altitudes, and high ambient pressure.

Risks to Family Members 

P/LP variants in the FLCN gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an FLCN P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial FLCN P/LP variant, and both males and females can pass it on to their children.

What You Should Know About BRIP1 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the BRIP1 gene are at an increased risk for cancers of the ovary.

Patients with BRIP1 P/LP variants receive specialized care at UTSouthwestern, which hosts one of the largest hereditary cancer programs in the nation.

Cancer Risks Associated with a BRIP1 Mutation

Individuals with a P/LP variant in the BRIP1 gene have up to a 15% chance of developing ovarian cancer in their lifetime. There is a potential increased risk for women with the variant to develop breast cancer, but data are conflicting. Rarely, individuals inherit two P/LP BRIP1 mutations and may develop a condition called Fanconi anemia, increasing the risk for other cancers and developmental differences.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Ovarian Cancer

• Gynecologic oncologists work with patients to determine a screening and management plan.
• Our specialists follow guidelines from the National Comprehensive Cancer Network(NCCN), including:
  • Consideration of surgery to remove the ovaries and fallopian tubes

Risks to family Members

P/LP variants in the BRIP1 gene are inherited in an autosomal dominant fashion. This means that parents, brothers, sisters, and children of individuals with a BRIP1 P/LP variant have a 1 in 2 or 50% chance of having the same variant. Both males and females can have and pass down P/LP variants in the BRIP1 gene. If two individuals have a BRIP1 P/LP variant, there is a 1 in 2 or 50% chance their child will have one variant and 1 in 4 or 25% chance their child will have both variants, consistent with a diagnosis of Fanconi anemia.

What You Should Know About CDC73 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the CDC73 gene may develop a CDC73-related condition, which includes a spectrum of several conditions that have overlapping features. The spectrum includes familial isolated hyperparathyroidism, parathyroid carcinoma, and hyperparathyroidism-jaw tumor (HPT-JT) syndrome. HPT-JT can cause primary hyperparathyroidism and cancer of the parathyroid glands. There is also an increased risk of developing kidney lesions, uterine tumors, and noncancerous tumors of the jawbone.

UTSW is proud to offer one of the most comprehensive hereditary cancer programs in the nation, delivering expert care to individuals with CDC73-related conditions.

Cancer Risks Associated with a CDC73 P/LP Variant

Not everyone with a CDC73 mutation will develop symptoms, but up to 90% will develop a CDC73-related condition.

Individuals with HPT-JT have up to a 95% chance of developing primary hyperparathyroidism by early adulthood and up to a 15% chance of parathyroid cancer. There is up to a 40% chance to develop noncancerous tumors of the jawbone, and up to 20% of individuals will develop kidney cysts or noncancerous kidney growths. Uterine tumors also appear to be more common.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Primary Hyperparathyroidism and Parathyroid Cancer

• Endocrinology specialists work with patients to establish appropriate surveillance and management.
• Our specialists may order blood and urine tests to monitor calcium, vitamin D, and hormone levels.

Other Cancers/Tumors

• UT Southwestern experts in urology, dentistry, and gynecology may also be an important part of the care team.
• Additional surveillance or management recommendations might include:
  • Kidney ultrasound every five years
  • Panoramic X-ray dental imaging
  • Pelvic exam or pelvic ultrasound

Risks to Family Members

P/LP variants in the CDC73 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a CDC73 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial CDC73 P/LP variant, and both males and females can pass it on to their children.

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the CHEK2 gene have an increased risk for cancers of the breast and prostate. Our knowledge of CHEK2 and the related cancer risk primarily comes from data on one specific pathogenic variant seen predominantly in individuals with Northern European ancestry (this variant is called c.1100del).

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

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the PTEN gene have PTEN hamartoma tumor syndrome (PHTS), which is a spectrum of several conditions that have overlapping features. PHTS can cause noncancerous, tumor-like growths called hamartomas throughout the body.

What You Should Know About DICER1 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the DICER1 gene have an increased risk for several different types of tumors, most commonly pleuropulmonary blastoma and cystic nephroma.

At UTSW, our hereditary cancer program is among the largest nationwide, with extensive experience supporting individuals carrying DICER1 P/LP variants.

Cancer Risks Associated with DICER1 P/LP Variants

The risk of an individual with a P/LP variant in the DICER1 gene to develop a tumor is unknown but thought to be low. DICER1-related tumors typically develop before age 40, with many tumors occurring in childhood.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Pleuropulmonary Blastoma (PPB)

• Specialists work with patients to determine appropriate surveillance and risk management for PPB.
• Our specialists follow established surveillance guidelines, including:
  • Initial chest CT
  • Consideration of chest radiographs

Cystic Nephroma and Wilms Tumor

• Urology specialists work with patients to determine appropriate surveillance and risk management for cystic nephroma and Wilms tumor.
• Our specialists follow established surveillance guidelines, including:
  • Consideration of abdominal ultrasound 

Ovarian Sertoli-Leydig Tumors, Gynandroblastomas, and Embryonal Rhabdomyosarcomas

• Gynecologic oncology specialists work with patients to determine appropriate surveillance and risk management for ovarian and uterine tumors.
• Our specialists follow established surveillance guidelines, including:
  • Consideration of annual or semiannual pelvic ultrasound

Ciliary Body Medulloepithelioma

• Ophthalmology specialists work with patients to determine appropriate surveillance and risk management for tumors of the eye.
• Our specialists follow established surveillance guidelines, including:
  • Consideration of annual evaluation

Other Cancer/Tumor Risks

• Specialists in otolaryngology, endocrinology, internal medicine, and other disciplines may also be an important part of the care team.
• Additional surveillance or management recommendations may include:
  • Annual thyroid physical exam

Additional screenings or starting screenings at a younger age might be considered, depending on personal risk factors and family history.

Risks to Family Members

P/LP variants in the DICER1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a DICER1 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial DICER1 P/LP variant, and both males and females can pass it on to their children.

Familial Adenomatous Polyposis (FAP) is a very rare condition that accounts for about 1% of new cases of colorectal cancer. At UT Southwestern, we have one of the largest hereditary cancer programs in the country and are experienced in working with individuals who have FAP.

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the CDKN2A gene have up to an 80% lifetime risk for melanoma, with risks varying based on geographic location. Individuals also have a greater than 15% lifetime risk for pancreatic cancer.

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

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FA Fact Sheet - English

FA Fact Sheet - Spanish

What You Should Know About PTCH1 or SUFU Pathogenic/Likely Pathogenic Variants 

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the PTCH1 gene or SUFU gene have nevoid basal cell carcinoma syndrome (NBCCS), also called basal cell nevus syndrome or Gorlin syndrome. These individuals have an increased risk of developing multiple basal cell carcinomas (skin cancers) and cysts in the jaw (keratocysts). They may also have characteristic physical features, including a larger than average head size; distinguishing facial features; abnormalities of the ribs, spine, or skull; and indentations in the palms of their hands or their feet.

UTSW has one of the nation’s most comprehensive hereditary cancer programs, and we specialize in caring for patients with PTCH1 or SUFU P/LP variants.

Cancer Risks Associated with a PTCH1 or SUFU P/LP Variant

Individuals with a P/LP variant in the PTCH1 gene or the SUFU gene have up to a 90% chance of developing basal cell skin cancer. In addition, it is estimated they have less than a 5% risk of developing medulloblastoma (brain cancer), which is usually diagnosed by the age 2. They may also have less than a 5% risk for benign tumors in the heart (cardiac fibromas), and females have a 20% risk for benign tumors in the ovaries (ovarian fibromas).

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

• Specialists work with patients to determine appropriate surveillance and risk management for individuals with NBCCS.
• Our specialists follow recommendations from the American Association for Cancer Research (AACR), including:
  • Annual skin examinations
  • Baseline echocardiogram in infancy
  • Dental exams with jaw X-ray
  • Ovarian ultrasound
• Individuals with NBCCS are very sensitive to radiation. It is important they avoid excessive sun exposure and that they not be treated with radiation therapy for cancer in order to reduce their risk for developing basal cell skin cancer.

Risks to Family Members

P/LP variants in the PTCH1 or SUFU gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a PTCH1 or SUFU P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial PTCH1 or SUFU P/LP variant, and both males and females can pass it on to their children.

What You Should Know About GREM1 Pathogenic/Likely Pathogenic Variants

Individuals with a certain type of variant in the GREM1 gene, called a duplication, have a condition called hereditary mixed polyposis syndrome (HMPS) and are at an increased risk of developing colorectal polyps (noncancerous growths) and colorectal cancer. This specific GREM1 duplication is common in individuals with Ashkenazi Jewish ancestry and is currently the only known variant in the GREM1 gene that is associated with increased cancer risks.

UTSW is one of the nation’s leading centers for genetic counseling and management of hereditary colorectal cancer syndromes, and we offer specialized care for individuals with GREM1 pathogenic variants.

Cancer Risks Associated with the GREM1 Pathogenic/Likely Pathogenic Duplication

There is currently limited information about the specific cancer risks for individuals with a GREM1 variant other than they have an increased risk for developing different types of colorectal polyps, including adenamatous polyps, hyperplastic polyps, and hamartomatous polyps. They also have up to a 20% risk of developing colorectal cancer.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Colorectal Polyps and Cancer

• Gastroenterology specialists work with patients to determine appropriate risk management for hereditary colorectal polyps and colorectal cancer.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Colonoscopy
  • Consideration of surgery if the polyp burden becomes unmanageable by colonoscopy

Risks to Family Members

Variants in the GREM1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a GREM1 variant have a 1 in 2 (or 50%) chance of having the variant as well. Both males and females can inherit a familial GREM1 variant, and both males and females can pass it on to their children.

Approximately 5-10% of breast cancer is inherited. Most hereditary breast cancers are caused by pathogenic/likely pathogenic (P/LP) variants in the BRCA1 and BRCA2 genes, but there are other genes that can cause inherited breast cancers.

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the CDH1 gene have an increased risk for a specific type of stomach cancer called diffuse or signet ring carcinoma. The lifetime risk for females with the variant to get this cancer is up to 35%, and for males with the variant it is up to 45%. Females with the variant also have up to a 55% lifetime risk for breast cancer.

What You Should Know About FH Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the FH gene have a condition called hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. HLRCC causes leiomyomas (noncancerous tumors) of the skin and uterus (otherwise known as uterine fibroids) and an increased risk for developing kidney cancer.

UTSW is recognized as a VHL Alliance Clinical Care Center (CCC). This designation emphasizes our commitment to providing outstanding, coordinated care for individuals with hereditary kidney cancer syndromes, including HLRCC.

Cancer Risks Associated with an FH P/LP Variant

Individuals with HLRCC have up to a 20% risk of developing kidney cancer. Most kidney tumors in individuals with HLRCC tend to be aggressive.

Most females with HLRCC have uterine fibroids. Usually, these fibroids are larger and more numerous and happen at a younger age than uterine fibroids in the general population (in other words, those not caused by HLRCC).

Most individuals with HLRCC present with a single or multiple leiomyomas of the skin (cutaneous). These are noncancerous and can appear as skin-colored to light brown bumps or raised areas of skin.

Rarely, individuals with HLRCC develop a pheochromocytoma (a tumor of the adrenal gland, which is located above the kidney) or paraganglioma (a tumor that begins in the nerve cells of the neuroendocrine system).

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Kidney Cancer

• Urology specialists work with patients to determine appropriate surveillance and risk management for hereditary kidney cancer.
• Our specialists follow established surveillance guidelines, including:
  • Annual abdominal MRI (preferred) or CT specific for kidney screening

Uterine Leiomyomas (Fibroids)

• Gynecology specialists work with patients to determine appropriate surveillance and risk management for uterine fibroids.
  • Annual gynecologic exam to assess severity of uterine fibroids and evaluate for cancerous changes
  • Consideration of pelvic ultrasound as needed
  • Consideration of myomectomy (removal of uterine fibroids) or hysterectomy (removal of uterus) for symptomatic fibroids

Skin Leiomyomas

• Dermatology specialists work with patients to determine surveillance and risk management for cutaneous leiomyomas.
• Annual full-body skin examination to assess the extent of disease and to evaluate for cancerous changes

Other tumors

• Specialists in endocrinology and other disciplines may also be an important part of the care team.
• Additional surveillance or management recommendations might include:
  • Consideration of biochemical screening (testing the blood/urine) and imaging studies (CT, MRI) for pheochromocytomas and paragangliomas

Risks to Family Members

P/LP variants in the FH gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an FH P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial FH P/LP variant, and both males and females can pass it on to their children.

Gene

More than 20 genes

Component Cancers/Tumors

Leukemia

Download Fact Sheet

Hereditary Leukemia Fact Sheet - English

Hereditary Leukemia Fact Sheet - Spanish

What You Should Know About MET Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the MET gene have a condition called hereditary papillary renal carcinoma and have an increased risk for kidney cancer.

With one of the largest hereditary cancer programs in the country, UTSW offers specialized care for patients with MET P/LP variants.

Cancer Risks Associated with a MET P/LP Variant

Individuals with a MET P/LP variant have a greater risk of getting a specific type of kidney cancer known as type 1 papillary renal carcinoma. The exact risk for kidney cancer is unknown; however, most people with a MET P/LP variant are expected to get kidney cancer at some point in their lifetime.

Kidney Cancer

• Kidney specialists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Imaging studies with MRI or CT every one to two years starting at age 30

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Individuals with hereditary paraganglioma-pheochromocytoma syndrome have an increased risk for developing neuroendocrine tumors called paragangliomas (PGLs) and pheochromocytomas (PCCs). Hereditary paraganglioma-pheochromocytoma syndrome is caused by pathogenic/likely pathogenic variants in the MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, and TMEM127 genes.

What You Should Know About RB1 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the RB1 gene have an increased risk for retinoblastoma, a cancer of the retina (part of the eye). Retinoblastoma can affect one or both eyes and can also occur in the brain, known as a pineoblastoma.

UTSW is proud to have one of the nation's largest hereditary cancer programs, specializing in individuals with RB1 P/LP variants.

Cancer Risks Associated with an RB1 P/LP Variant

Individuals with an RB1 P/LP variant may have up to a 100% lifetime risk for retinoblastoma, with risks varying based on the location of the P/LP variant in the RB1 gene. Individuals also have a 2-5% lifetime risk for pinoeblastoma. People with RB1 P/LP variants also have risk for other cancers outside the eye, including bone tumors, soft tissue sarcomas, and melanoma skin cancers.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Retinoblastoma

• Eye specialists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the American Association of Ophthalmic Oncologists and Pathologists, including:
  • Routine eye exams beginning at birth (with the type of eye exam and how often changing with age)
  • Brain MRI

Other Cancers

• Specialists in internal medicine, surgical oncology, and other fields of expertise may also be an important part of the care team.
• Additional surveillance or management recommendations may include:
  • Annual physical exams and skin exams
  • Consideration of additional screenings or earlier ages of screenings based on personal risk factors and family history

Risks to Family Members

P/LP variants in the RB1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an RB1 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial RB1 P/LP variant, and both males and females can pass it on to their children.

What You Should Know About HOXB13 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the HOXB13 gene have an increased risk for prostate cancer.

At UTSW, we host one of the nation's largest hereditary cancer programs, offering specialized care for individuals with HOXB13 P/LP variants.

Cancer Risks Associated with HOXB13 P/LP Variants

Individuals who have a prostate have up to a 60% lifetime risk for prostate cancer. Currently, it is unknown if there is an increased risk for other cancers in individuals with an HOXB13 P/LP variant.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Prostate Cancer

• Our primary care providers and specialists work with patients to establish appropriate prostate cancer surveillance.
• They may recommend a baseline blood test to check PSA levels at age 40.
• Additional screenings or starting screenings at a younger age might be considered, depending on personal risk factors and family history.

Risks to Family Members

P/LP variants in the HOXB13 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a HOXB13 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial HOXB13 P/LP variant, and both males and females can pass it on to their children.

What You Should Know About HOXB13 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the BMPR1A gene have a hereditary cancer syndrome called juvenile polyposis syndrome (JPS). Individuals with this P/LP variant have an increased risk for gastrointestinal (GI) tract polyps and cancers. The term “juvenile” refers to the type of polyp rather than the age the polyps begin.

With one of the nation’s leading hereditary cancer programs, UTSW offers expert evaluation and personalized care for individuals with BMPR1A mutations.

Cancer Risks Associated with a BMPR1A P/LP Variant

Individuals with a BMPR1A P/LP variant have up to a 50% lifetime risk for colon cancer and may be more likely than average to develop stomach or small intestine cancers, although these cancers are rare and the risk is undefined with BMPR1A P/LP variants.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people receive appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

GI Polyps and Cancer

• GI specialists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • High-quality colonoscopy and upper endoscopy
  • Consideration of surveillance for small intestine cancer (at the discretion of your GI provider)

Other Cancers

• Specialists in internal medicine, surgical oncology, and other disciplines may also be an important part of the care team.
• Additional screenings or earlier ages of screenings may be considered based on personal risk factors and family history.

Risks to Family Members

P/LP variants in the BMPR1A gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a BMPR1A P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial BMPR1A P/LP variant, and both males and females can pass it on to their children.

What You Should Know About KIT Pathogenic/Likely Pathogenic Variants

Some pathogenic/likely pathogenic (P/LP) variants in the KIT gene are associated with piebaldism, while other P/LP variants in the KIT gene are associated with gastrointestinal stromal tumors (GISTs) and familial mastocytosis. Piebaldism is associated with lighter than normal patches of hair and skin that are present at birth. GISTs are tumors in the gastrointestinal tract that can be cancerous (malignant) or noncancerous (benign). Mastocytosis is a blood disorder that occurs when white blood cells called mast cells build up in tissue, causing an increased immune response.

With one of the largest hereditary cancer programs in the country, UTSW has significant experience in managing individuals with KIT gene P/LP variants.

Cancer Risks Associated with a KIT P/LP Variant

Individuals with a KIT P/LP variant may have an increased risk for developing GISTs, but the exact risk is unknown. As we continue to learn more about the KIT gene and its associated cancer risks, we may learn there are increased risks for other types of cancers.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people receive appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

The UTSW GCPC team can review your genetic testing, as well as your personal and family history of cancer, to determine your cancer screening recommendations. The team may suggest earlier screenings or specialized screenings.

Examples of potential cancer screenings include:

• Colonoscopies
• Upper endoscopies
• Abdominal imaging including CT scan or MRI

Risks to Family Members

P/LP variants in the KIT gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a KIT P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial KIT P/LP variant, and both males and females can pass it on to their children.

Li-Fraumeni syndrome is caused by pathogenic/likely pathogenic (P/LP) variants in the TP53 gene. Individuals with a P/LP variant in the TP53 gene have an increased risk for a broad spectrum of cancers. The most common cancer types seen include breast cancer, brain cancer, blood or hematologic cancers, sarcomas, and tumors of the adrenal gland (adrenocortical carcinoma).

Lynch syndrome is an inherited cancer risk condition that increases a person’s chances of developing multiple types of cancer. It is caused by mutations, or breaks, of the MLH1, MSH2, MSH6, PMS2, or EPCAM genes, which support the ability of the cells’ DNA (genetic code) to repair itself and protect against cancer.

What You Should Know About MC1R Pathogenic/Likely Pathogenic Variants

Individuals with a single pathogenic/likely pathogenic (P/LP) variant in the MC1R gene may have an increased risk for skin cancer, particularly melanoma.

Individuals with two P/LP variants in the MC1R gene (one inherited from each parent) may have a chance for red hair and a fairer skin tone.

UTSW is home to one of the nation’s largest hereditary cancer programs, offering extensive expertise in working with individuals carrying MC1R P/LP variants.

Cancer Risks Associated with an MC1R P/LP Variant

The cancer risks for individuals who have an MC1R P/LP variant are still being understood. However, it has been suggested that individuals with one P/LP variant in the MC1R gene may be at an increased risk of developing skin cancer, particularly melanoma, regardless of skin damage or skin tone. Researchers are actively investigating how MC1R P/LP variants, environmental factors, and melanoma risks are interconnected.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

There are no consensus recommendations on the frequency and method of cancer surveillance someone with a P/LP variant in the MC1R gene should have. Individuals may consider a formal dermatological evaluation based on the increased chance of developing skin cancer.

Alongside our dermatology colleagues, the UTSW GCPC team can review your genetic testing, as well as your personal and family history of cancer, to help determine your cancer screening recommendations. The team may suggest earlier screenings or specialized screenings.

Risks to Family Members

P/LP variants in the MC1R gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with one MC1R P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial MC1R P/LP variant, and both males and females can pass it on to their children. If both parents have a P/LP variant in MC1R, their children have a 25% chance to have two P/LP variants in MC1R, a 50% chance to have one P/LP variant, and a 25% chance to have none.

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

What You Should Know About MEN1 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the MEN1 gene have a condition called multiple endocrine neoplasia, type 1. MEN1 is associated with an increased risk for several types of endocrine tumors, primarily involving the parathyroid, pancreas, and pituitary gland. These tumors can be benign (noncancerous) or malignant (cancerous).

As a leader in hereditary cancer care, UTSW boasts a large program with deep experience in caring for individuals with MEN1 P/LP variants.

Cancer Risks Associated with a MEN1 P/LP Variant

Individuals with a MEN1 P/LP variant have the following risks:

• Parathyroid Tumors (can present as primary hyperparathyroidism): nearly 100% by age 50
• Pituitary Tumor: up to a 40% lifetime risk
• Tumors of the Gastroenteropancreatic (GEP) Tract: up to a 40% lifetime risk
• Carcinoid (Bronchial and Thymic Cancer): up to a 10% lifetime risk
• Adrenocortical Cancer: up to a 40% lifetime risk

MEN1 can also be associated with non-endocrine tumors, including: skin findings, central nervous system tumors, leiomyomas, thyroid tumors, and breast cancer.

Managing Cancer Risks 

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Endocrine Tumors

• Endocrinologists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Biochemical workup (such as blood work) to check levels of specific hormones, proteins, glucose, and calcium
  • Consideration of imaging such as abdominal/pelvis CT or MRI with contrast, serial EUS, pituitary or sella MRI with contrast, chest CT or MRI with contrast

The frequency of blood work and imaging may vary based on results. Additional screenings or starting screening at a younger age might be considered based on personal risk factors and family history.

Risks to Family Members

The majority (90%) of patients with a MEN1 P/LP variant have an affected parent, but 10% have a de novo variant, meaning it was spontaneous and not inherited. De novo variants can be passed on to children. P/LP variants in the MEN1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a MEN1 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial MEN1 P/LP variant, and both males and females can pass it on to their children.

What You Should Know About RET Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the RET gene have multiple endocrine neoplasia type 2 (MEN2), which increases the risk for thyroid cancer, pheochromocytomas, and hyperparathyroidism.

UTSW is home to one of the largest hereditary cancer programs in the country, with specialized expertise in the clinical management of patients carrying P/LP variants of the RET gene.

Cancer Risks Associated with a RET P/LP Variant

Individuals with a RET P/LP variant have an increased risk for a specific type of thyroid cancer called medullary thyroid cancer. Depending on the specific RET variant that someone has, the risk for medullary thyroid cancer is up to 95%. Individuals also have up to a 35% risk for a type of adrenal tumor called pheochromocytoma and up to a 30% risk for hyperparathyroidism.

Managing Cancer Risks 

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Thyroid Cancer

• Our endocrinologists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the American Thyroid Association, including:
  • Annual physical exam, neck ultrasound, and blood work
  • Consideration of prophylactic thyroidectomy
  • Annual measurement of plasma or 24-hour urinary fractionated metanephrines
  • Annual biochemical screening of albumin-corrected calcium or ionized serum calcium measurements
• The recommended age of surveillance and surgery depends on the specific RET variant but may begin as early as age 3.

Risks to Family Members

P/LP variants in the RET gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a RET P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial RET P/LP variant, and both males and females can pass it on to their children.

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

What You Should Know About NF1 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the NF1 gene have neurofibromatosis 1. Features of NF1 include skin findings (café au lait macules, axillary and inguinal freckling, and neurofibromas), Lisch nodules (benign tumors of the eye), and optic gliomas (brain tumors). While most tumors associated with NF1 are benign, individuals with NF1 have an increased risk of various cancers.

At UTSW, we operate one of the largest hereditary cancer programs in the country, with specialized expertise in the clinical management of patients carrying P/LP variants of the NF1 gene.

Cancer Risks Associated with an NF1 Mutation

Almost all (99%) individuals with an NF1 P/LP variant will develop multiple benign neurofibromas of the skin, which are tumors that grow within a nerve. Approximately 30% of people with NF1 will develop plexiform neurofibromas, which happen under the skin, and up to ~15% of individuals will develop malignant peripheral nerve sheath tumors (MPNSTs), which are more aggressive and happen in the protective layers of nerves. Individuals with NF1 have up to a 20% chance of developing an optic glioma, a 5% chance to develop a non-optic glioma, and may have an increased risk for pheochromocytomas, which are tumors of the adrenal glands. There is also up to a 40% risk for breast cancer and a suspected increased risk for gastrointestinal stromal tumors (GISTs) and leukemia/lymphoma.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Neurofibromas

• Dermatologists and genetic specialists work with patients to determine appropriate surveillance and risk management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Annual physical exam
  • Imaging, if clinically indicated

Optic Gliomas

• Ophthalmologists work with patients to determine appropriate surveillance and risk management for optic gliomas
• Recommendations often include:
  • Annual ophthalmologic exam until adolescence, as needed in older childhood

Breast Cancer

• Breast specialists work with patients to determine appropriate breast cancer surveillance and risk management.
• Our specialists follow recommendations from the NCCN, including:
  • Annual mammography with consideration of breast MRI with and without contrast starting at age 30

Other Features

• Specialists in neurology, oncology, orthopedics, speech/occupational/physical therapy, and other disciplines may also be an important part of your care team.
• Additional surveillance or management recommendations might include:
  • Blood pressure monitoring, evaluation of musculoskeletal system, and developmental assessments

Additional screenings or starting screenings at a younger age might be considered based on personal risk factors and family history.

Risks to Family Members

P/LP variants in the NF1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an NF1 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Approximately 50% of individuals with an NF1 variant did not inherit the variant from a parent (i.e., the variant is new in the patient or de novo). Both males and females can inherit a familial NF1 P/LP variant, and both males and females can pass it on to their children.

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

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the PALB2 gene have an increased risk for cancers of the breast, ovary, and pancreas. Females with a PALB2 P/LP variant have up to a 55% lifetime risk for breast cancer and males have up to a 10% lifetime risk for breast cancer. Females with the variant have up to a 5% lifetime risk for ovarian cancer. Males and females with the variant have up to a 5% risk for pancreatic cancer.

What You Should Know About STK11 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the STK11 gene have Peutz-Jeghers syndrome (PJS) and its associated increased risks for gastrointestinal polyps and cancers, as well as breast, pancreatic, cervical, uterine, ovarian, testicular, and lung cancers. Individuals with PJS can have hyperpigmentation (freckling) on the fingers and nose and around the mouth, eyes, and perianal area, which typically is more pronounced in childhood, later fading in puberty and adulthood.

With one of the most comprehensive hereditary cancer programs in the country, UT Southwestern has extensive experience supporting individuals with PJS.

Cancer Risks Associated with an STK11 P/LP Variant

Females with an STK11 P/LP variant may have up to a 55% lifetime risk for breast cancer. They are also at an increased risk for gynecologic cancers, including more than a 10% lifetime risk for cervical (typically minimal deviation adenocarcinoma) cancer, a 10% lifetime risk for uterine cancer, and more than a 10% lifetime risk for ovarian sex cord/Sertoli cell tumors. Males have a 10% lifetime risk for testicular cancer, typically sex cord/Sertoli cell tumors. Males and females have a high risk for developing gastrointestinal polyps and cancers, including a 40% lifetime risk of developing colon cancer, a 30% lifetime risk of developing stomach cancer, a 15% lifetime risk of developing small bowel cancer, and a 10-35% lifetime risk of developing pancreatic cancer. Individuals also have up to a 20% lifetime risk of developing lung cancer.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Gastrointestinal Polyps and Cancers

• Gastroenterology specialists work with patients to determine appropriate risk management for hereditary gastrointestinal polyps and colon, stomach, small bowel, and pancreatic cancers.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Screening starting at age 8 and continuing at least every three years if polyps are found. If no polyps are found in childhood, screening resumes at age 18 and continues at least every three years.
    • Colonoscopy for colon cancer
    • Upper endoscopy (EGD) for stomach cancer
    • Small bowel visualization (video capsule endoscopy or CT/MRI enterography) for small intestine cancer
  • MRI/magnetic resonance cholangiopancreatography and/or endoscopic ultrasound of the pancreas beginning at age 30, continuing annually.

Female Breast Cancer

• Breast specialists work with patients to determine appropriate surveillance and risk management for hereditary breast cancer.
• Our specialists follow NCCN recommendations, including:
  • Clinical breast exams and screening by yearly mammograms and breast MRI
  • Consideration of bilateral mastectomies, which can reduce the risk of breast cancer

Gynecologic Cancer

• Gynecologic oncology specialists work with patients to determine appropriate surveillance and risk management for hereditary ovarian, cervical, and uterine cancers.
• Our specialists follow NCCN recommendations, including:
  • Annual physical examination for observation of precocious puberty
  • Annual pelvic examination with pelvic ultrasound and Pap smear
  • Consideration of removal of the ovaries, uterus, and cervix once childbearing is complete

Other Cancers

• Specialists in internal medicine and other disciplines may also be an important part of the care team.
• Additional surveillance or management recommendations may include:
  • Annual exam for male patients, including observation for feminizing changes
  • Smoking cessation and education regarding lung cancer symptoms

Risks to Family Members

P/LP variants in the STK11 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a STK11 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial STK11 P/LP variant, and both males and females can pass it on to their children.

What You Should Know About POLD1 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the POLD1 gene have polymerase proofreading-associated polyposis (PPAP) syndrome, which means they have an increased risk for gastrointestinal polyps and colon cancer.

Some individuals with a P/LP variant in the POLD1 gene may also have autosomal dominant mandibular hypoplasia, deafness, early aging, and lipodystrophy (MDPL) syndrome. MDPL is a rare, systemic disorder characterized by the loss of subcutaneous fat, distinctive facial features, and metabolic abnormalities including insulin resistance and diabetes.

At UT Southwestern, patients with a P/LP variant in the POLD1 gene benefit from the expertise of one of the country’s largest and most experienced hereditary cancer programs.

Cancer Risks Associated with a POLD1 P/LP Variant

Individuals with a POLD1 P/LP variant have an increased risk of developing gastrointestinal polyps called adenomas, a type of precancerous polyp, in the colon. Individuals are also believed to have at least a 20% lifetime risk of developing colon cancer.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Gastrointestinal Polyps and Colon Cancer

• Gastroenterology specialists work with patients to determine appropriate risk management for hereditary gastrointestinal polyps and colon cancer.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Colonoscopy every one to two years
  • Consideration of surgery if the polyp burden becomes unmanageable by colonoscopy

Risks to Family Members

P/LP variants in the POLD1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a POLD1 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial POLD1 P/LP variant, and both males and females can pass it on to their children.

What You Should Know About POLE Pathogenic/Likely Pathogenic Variants

Pathogenic/likely pathogenic (P/LP) variants in the POLE gene are associated with autosomal dominant polymerase proofreading-associated polyposis (PPAP) syndrome, as well as autosomal recessive facial dysmorphism-immunodeficiency-livedo-short stature (FILS) syndrome and IMAGE-I syndrome. The type of P/LP variant in the POLE gene determines the features/cancer risks the individual may have. Our genetic counselors can help you determine which features/cancer risks you may have based on your specific variant.

Examples of these features/cancer risks are:

• PPAP syndrome increases the risk for gastrointestinal polyps and colon cancer.
• FILS syndrome is a rare condition associated with unique facial features, immunodeficiency, skin findings such as discoloration of the skin that may lead to an increased risk for skin cancer, and short stature.
• IMAGE-I syndrome is associated with intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, immunodeficiency, and diffuse, large B-cell lymphoma.

Patients with POLE P/LP variants can count on UT Southwestern for personalized care from one of the most trusted hereditary cancer programs in the country.

Cancer Risks Associated with a POLE P/LP Variant

Individuals with a POLE P/LP variant associated with PPAP have an increased risk for developing gastrointestinal polyps called adenomas, a type of precancerous polyp, in the colon. They are also believed to have at least a 20% lifetime risk of developing colon cancer.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Gastrointestinal Polyps and Colon Cancer

• Gastroenterology specialists work with patients to determine appropriate risk management for hereditary gastrointestinal polyps and colon cancer.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Colonoscopy every one to two years
  • Consideration of surgery if the polyp burden becomes unmanageable by colonoscopy

Risks to Family Members

P/LP variants in the POLE gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a POLE P/LP variant have a 1 in 2 (50%) chance of having the P/LP variant as well. Both males and females can inherit a familial POLE P/LP variant, and both males and females can pass it on to their children.

What You Should Know About RAD51C Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the RAD51C gene are at an increased risk for cancers of the breast and ovary.

As one of the largest hereditary cancer programs in the country, UT Southwestern offers specialized care for patients with RAD51C P/LP variants.

Cancer Risks Associated with a RAD51C Mutation

Females with a P/LP RAD51C variant have approximately a 20% risk of developing breast cancer and up to a 15% risk of developing ovarian cancer over their lifetime. Individuals who inherit two P/LP RAD51C mutations may develop a condition called Fanconi anemia (FA), increasing the risk for childhood leukemia and other cancers as well as developmental differences.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Breast Cancer

• Breast specialists at UT Southwestern work with patients to determine individual screening and surgical management.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Annual mammogram and breast MRI

Ovarian Cancer

• Gynecologic oncologists work with patients to determine a surveillance and management plan for hereditary ovarian cancer.
• Our specialists follow recommendations from the NCCN, including:
  • Surgery to remove the ovaries and fallopian tubes

Surveillance or management may be recommended at an earlier age depending on family history of cancer and personal risk factors.

Risks to family Members

P/LP variants in the RAD51C gene are inherited in an autosomal dominant fashion. This means that parents, brothers, sisters, and children of individuals with a RAD51C P/LP variant have a 1 in 2 or 50% chance of having the same variant. Both males and females can have and pass down P/LP variants in the RAD51C gene. If two individuals have a P/LP RAD51C variant, there is a 1 in 2 or 50% chance their child will have one variant and 1 in 4 or 25% chance their child will have both variants, consistent with a diagnosis of FA.

What You Should Know About RAD51D Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the RAD51D gene have an increased risk of developing breast cancer, ovarian cancer, and potentially prostate cancer.

With nationally recognized expertise in hereditary cancers, UT Southwestern is proud to offer specialized care tailored to individuals with a P/LP variant in the RAD51D gene.

Cancer Risks Associated with a RAD51D P/LP Variant

Females with a RAD51D P/LP variant have an approximate lifetime risk of 20% for developing breast cancer. They also have up to a 20% lifetime risk of developing ovarian cancer.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Female Breast Cancer

• Breast specialists work with patients to determine appropriate surveillance and risk management for hereditary breast cancer.
• Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
  • Annual mammogram with consideration of annual breast MRI

Ovarian Cancer

• Gynecologic oncology specialists work with patients to determine appropriate surveillance and risk management for hereditary ovarian cancer.
• Our specialists follow NCCN recommendations, including:
  • Consideration of surgery to remove the ovaries and fallopian tubes

Risks to Family Members

P/LP variants in the RAD51D gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a RAD51D P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial RAD51D P/LP variant, and both males and females can pass it on to their children.

What You Should Know About SMARCA4 Pathogenic/Likely Pathogenic Variants

Certain pathogenic/likely pathogenic (P/LP) variants in the SMARCA4 gene cause rhabdoid tumor predisposition syndrome (RTPS) while other P/LP variants cause Coffin-Siris syndrome. Rhabdoid tumors are tumors of soft tissue that most often occur in the kidney, brain, and nervous system. RTPS also increases the risk for a specific type of ovarian cancer called small cell carcinoma of the ovary hypercalcemic type (SCCOHT). Individuals with Coffin-Siris syndrome may have developmental delay and distinct facial features.

At UTSW, our renowned hereditary cancer program – one of the largest in the nation – provides expert care for those with SMARCA4 P/LP variants.

Cancer Risks Associated with a SMARCA4 Mutation

Individuals with a SMARCA4 variant are at an increased risk of developing cancerous tumors called rhabdoid tumors. These tumors often occur in the brain and the kidney but can also develop in other organs and soft tissues of the body. Rhabdoid tumors typically occur in infancy (< 3 years of age). Women with the variant are also at an increased risk of developing SCCOHT.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Rhabdoid Tumors

• Pediatric specialists work with patients to establish appropriate surveillance.
• Specialists may consider neurological exams and frequent imaging using ultrasound and/or MRI.

Ovarian Cancer (SCCOHT)

• Gynecologic oncology specialists work with patients to establish a personalized ovarian cancer surveillance or surgical plan.
• Our specialists follow American Association for Cancer Research (AACR) recommendations, including:
  • Abdominal and pelvic ultrasounds
  • Consideration of surgical removal of the ovaries

Risks to Family Members

P/LP variants in the SMARCA4 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a SMARCA4 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. However, most individuals with a SMARCA4 P/LP variant inherited it from an unaffected, healthy parent.

What You Should Know About TSC1 and TSC2 Pathogenic/Likely Pathogenic Variants

Individuals with a pathogenic/likely pathogenic (P/LP) variant in the TSC1 or TSC2 gene have tuberous sclerosis complex (TSC) and develop noncancerous tumors throughout the body, most commonly in the skin, brain, kidneys, lungs, heart, and eyes. Individuals with TSC are also at an increased risk of developing kidney cancer.

UTSW has one of the nation’s leading hereditary cancer programs, and we deliver specialized care for individuals with TSC.

Cancer Risks Associated with a TSC1 and TSC2 Mutations

Almost all individuals with TSC will have skin findings, such as light spots called hypomelanotic macules, shagreen patches (areas of raised and thickened skin), and ungual fibromas (growths under the nail). Up to 90% of individuals will have brain findings, such as growths in the outer surface of the brain known as cortical tubers. Kidney disease, including noncancerous tumors known as angiomyolipomas, occur in up to 80% of individuals with TSC. Individuals with TSC are also at an increased risk of developing kidney cancer. Up to 40% will develop lung disease (lymphangiomyomatosis), and up to 70% will have noncancerous tumors of the heart. Individuals with TSC can also develop benign tumors of the retina known as hamartomas.

Managing Cancer Risks

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

Skin Findings

• Dermatology specialists work with patients to establish personalized skin surveillance plans.
• Our specialists typically recommend annual skin exams.

Brain Tumors

• Neurology specialists work with patients to determine appropriate surveillance and personalized management for brain findings and symptoms.
• Surveillance may include brain MRIs every one to three years.

Kidney Cancer

• Urology specialists work with patients to establish appropriate surveillance and risk management for kidney cancers and other noncancerous kidney tumors.
• Our specialists follow the National Comprehensive Cancer Network (NCCN) recommendations, including:
  • Abdominal MRI every one to three years

Other Cancers/Tumors

• UT Southwestern experts in pulmonology, cardiology, and ophthalmology may also be an important part of the care team.
• Additional surveillance or management recommendations may include:
  • Pulmonary function tests and chest imaging
  • Echocardiogram (ultrasound of the heart)
  • Eye exam

Risks to Family Members

P/LP variants in the TSC1 and TSC2 genes are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a TSC1 or TSC2 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. It is important to acknowledge that approximately two-thirds of individuals with a TSC1 or TSC2 P/LP variant did not inherit it from a parent but can pass it on to their children. Both males and females can inherit a familial TSC1 or TSC2 P/LP variant, and both males and females can pass it on to their children.

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

VHL Fact Sheet - English

VHL Fact Sheet - Spanish

Download Clinical Guide

VHL Clinical Guide