Lynch Syndrome

Genetic or hereditary cancers are caused by mutations in genes that typically are inherited through families. It is estimated that 5%-10% of all cancers have a genetic component.

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.

People with Lynch syndrome often develop cancer as early as in their 20s and throughout their lifetime. Their children have a 50% chance of inheriting Lynch syndrome.

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.

MLH1

What You Should Know About Lynch Syndrome (MLH1 P/LP Variants)

Lynch syndrome is the most common type of hereditary colon cancer and accounts for 2-4% of all colon cancers. At UT Southwestern, we have one of the largest hereditary cancer programs in the country and have identified and worked with approximately 1,000 individuals with this genetic disease. Lynch syndrome is caused by pathogenic/likely pathogenic (P/LP) variants in one of five different genes, including MLH1. The specific cancer risks and care recommendations depend on which of the genes is the source.

Cancer Risks Associated with Lynch Syndrome (MLH1 P/LP Variants)

People with Lynch syndrome due to a P/LP variant in the MLH1 gene have up to a 65% risk of developing colorectal cancer throughout their lifetime. Females have up to a 55% risk for uterine cancer and up to a 20% risk for ovarian cancer. Males and females with Lynch syndrome also have an increased risk for other types of cancer, including stomach, small bowel, pancreatic, urothelial, bladder, prostate, and brain cancers. These cancers tend to occur at a younger age.

Managing the Cancer Risks

• Colon Cancer
  • Our gastroenterology specialists work with patients to establish a personalized colon cancer surveillance plan.
  • Our specialists follow National Comprehensive Cancer Network (NCCN) recommendations, including:
    • Colonoscopy every one to two years, starting at age 20-25
• Uterine/Ovarian Cancer
  • Our gynecology oncology specialists work with patients to determine appropriate risk management for hereditary gynecologic cancers.
  • Our specialists follow NCCN recommendations, including:
    • Removal of ovaries and uterus after childbearing is complete
    • Consideration of uterine cancer screening via uterine biopsy and transvaginal ultrasound
    • Consideration of ovarian cancer screening via CA-125 blood test and transvaginal ultrasound
• Other Cancers
  • UT Southwestern experts in internal medicine, surgical oncology, and other specialties may also be an important part of the care team.
  • Additional surveillance or management recommendations might include:
  • Consideration of annual urinalysis beginning at age 30-35
    • Upper endoscopy every two to four years, beginning at age 30-40
    • Annual abdominal MRI and/or upper endoscopy beginning at age 50 if a family history of pancreatic cancer
    • Consideration of annual prostate screening starting at age 40
    • Consideration of additional screenings or starting screenings at a younger age, depending on personal risk factors and family history

Risk to Family Members

P/LP variants in the MLH1 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an MLH1 variant have a 1 in 2 (50%) chance of having the variant as well. Both males and females can inherit a familial MLH1 variant and can pass it on to their children. When an individual inherits two MLH1 P/LP variants (one from each parent), this causes a syndrome called constitutional mismatch repair deficiency (CMMRD). CMMRD is associated with an increased risk for childhood colon cancer, lymphoma, brain tumors, and café au lait spots.

MSH6

What You Should Know About Lynch Syndrome (MSH6 P/LP Variants)

Lynch syndrome is the most common type of hereditary colon cancer and accounts for 2-4% of all colon cancers. At UT Southwestern, we have one of the largest hereditary cancer programs in the country and have identified and worked with nearly 1,000 individuals with this genetic disease. Lynch syndrome is caused by pathogenic/likely pathogenic (P/LP) variants in one of five different genes, including MSH6. The specific cancer risks and care recommendations depend on which of the genes is the source.

Cancer Risks Associated with Lynch Syndrome (MSH6 P/LP Variants)

People with Lynch syndrome due to a P/LP variant in the MSH6 gene have up to a 45% risk of developing colorectal cancer in their lifetime. Females have up to a 50% risk for uterine cancer and up to a 13% risk for ovarian cancer. Males and females with an MSH6 variant may also have an increased risk for other types of cancer, including stomach, small bowel, urothelial, and bladder cancer. These cancers tend to occur at a younger age.

Managing the Cancer Risks

• Colon Cancer
  • Our gastroenterology specialists work with patients to establish a personalized colon cancer surveillance plan.
  • Our specialists follow National Comprehensive Cancer Network (NCCN) recommendations, including:
    • Colonoscopy every one to two years starting at age 30-35
• Uterine Cancer
  • Our gynecology oncology specialists work with patients to determine appropriate risk management for hereditary gynecologic cancers.
  • Our specialists follow NCCN recommendations, including:
    • Removal of the uterus after childbearing is complete
    • Consideration of uterine screening via uterine biopsy and transvaginal ultrasound
• Other Cancers
  • UT Southwestern experts in internal medicine, surgical oncology, and other specialties may also be an important part of the care team.
  • Additional surveillance or management recommendations might include:
    • Consideration of annual urinalysis beginning at age 30-35
    • Upper endoscopy every two to four years, beginning at age 30-40
    • Annual abdominal MRI and/or upper endoscopy beginning at age 50 if a family history of pancreatic cancer
    • Consideration of additional screenings or starting screenings at a younger age, depending on personal risk factors and family history

Risk to Family Members

P/LP variants in the MSH6 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an MSH6 mutation have a 1 in 2 (50%) chance of having the mutation as well. Both males and females can inherit a familial MSH6 mutation and can pass it on to their children. When an individual inherits two MSH6 mutations (one from each parent), this causes a syndrome called constitutional mismatch repair deficiency (CMMRD). CMMRD is associated with an increased risk for childhood colon cancer, lymphoma, brain tumors, and café au lait spots.

EPCAM

What You Should Know About Lynch Syndrome (EPCAM P/LP Variants)

Lynch syndrome is the most common type of hereditary colon cancer, meaning the risk can be passed down from parents to their children. At UT Southwestern, we have one of the largest hereditary cancer programs in the country and have identified and worked with nearly 1,000 individuals with this genetic disease. Lynch syndrome makes up 2-4% of all colon cancers and is caused by pathogenic/likely pathogenic (P/LP) variants in one of five different genes, including EPCAM. The specific cancer risks and care recommendations depend on which of the genes is the source.

Cancer Risks Associated with Lynch Syndrome (EPCAM P/LP Variants)

People with Lynch syndrome due to a pathogenic/likely pathogenic (P/LP) variant in the EPCAM gene have up to a 55% risk of developing colorectal cancer in their lifetime. Females have up to a 60% risk for uterine cancer and up to a 40% risk for ovarian cancer. Males have a greater risk for prostate cancer. Males and females with EPCAM mutations also have a greater risk for other types of cancer, such as stomach cancer, small bowel cancer, and bladder cancer. These cancers tend to happen at a younger age.

Managing the Cancer Risks

• Colon Cancer
  • Our gastroenterology specialists work with patients to establish a personalized colon cancer surveillance plan.
  • Our specialists follow National Comprehensive Cancer Network (NCCN) recommendations, including:
    • Colonoscopy every one to two years, starting at age 20-25
• Uterine/Ovarian Cancer
  • Our gynecology oncology specialists work with patients to determine appropriate risk management for hereditary gynecologic cancers.
  • Our specialists follow NCCN recommendations, including:
    • Removal of ovaries and uterus after childbearing is complete
    • Consideration of uterine cancer screening via uterine biopsy and transvaginal ultrasound
    • Consideration of ovarian cancer screening via CA-125 blood test and transvaginal ultrasound
• Other Cancers
  • UT Southwestern experts in internal medicine, surgical oncology, and other specialties may also be an important part of the care team.
  • Additional surveillance or management recommendations might include:
    • Consideration of annual urinalysis beginning at age 30-35
    • Upper endoscopy every two to four years, beginning at age 30-40
    • Annual abdominal MRI and/or upper endoscopy beginning at age 50 if a family history of pancreatic cancer
    • Consideration of annual prostate screening starting at age 40
    • Consideration of additional screenings or starting screenings at a younger age, depending on personal risk factors and family history

Risk to Family Members

P/LP variants in the EPCAM gene are inherited. This means that children, brothers, sisters, and parents of individuals with an EPCAM mutation have a 1 in 2 (50%) chance of having the mutation. Both males and females can inherit an EPCAM mutation and can pass it on to their children. Very occasionally, a person gets two EPCAM mutations (one from each parent). This causes a syndrome called congenital tufting enteropathy (CTE). CTE is a rare chronic diarrheal disorder that is seen in infancy.