Hereditary Cancer Syndromes > Lynch Syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM)

Cancer Risks

Additional Cancer Risks

Second Cancer Risks

Cancer Risks

MLH1 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 70 52%-82% 1.8%
Endometrial To age 70 25%-60% 1.7%
Overall cancer risk (Lynch cancers) Risk for second Lynch-related cancer after a first cancer diagnosis Increased risk NA
Ovarian To age 70 4%-12% 0.7%
Gastric To age 70 6%-13% 0.4%
Small Bowel To age 70 3%-6% 0.1%
Urinary Tract To age 70 5%-7% 0.7%
Pancreatic To age 70 1%-6% 0.5%
Hepatobiliary Tract To age 70 1.4%-4% 0.5%
Central Nervous System To age 70 1%-3% 0.4%
Sebaceous Neoplasms To age 70 1%-9% <1.0%
Prostate To age 80 Up to 30% 10.9%

MLH1 Cancer Risk Management Table

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy 20 to 25 years, or 2 to 5 years younger than the earliest diagnosis in family if it is under age 25 Every 1 to 2 years
  Colorectal surgical evaluation may be appropriate for some patients Individualized NA
  Consider the use of aspirin as a risk reduction agent Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms. Individualized NA
  Consider pelvic examination, endometrial sampling and transvaginal ultrasound. 30 to 35 years Annually
  Consider hysterectomy. After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy. Age 40 or after completion of childbearing NA
  Consider transvaginal ultrasound and CA-125 measurement. 30 to 35 years NA
  Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives). Individualized NA
  Patient education about ovarian cancer symptoms Individualized NA
Gastric Consider testing and treating Helicobacter pylori infection. Individualized NA
  Consider upper endoscopy, particularly for patients with additional risk factors for gastric cancer, such as family history or Asian ancestry. Consider biopsy of the antrum. 30 to 40 years Every 2 to 5 years
Small Bowel Consider upper endoscopy, particularly for patients with additional risk factors for small bowel cancer, such as family history. 30 to 40 years Every 3 to 5 years
Urinary Tract Consider urinalysis. 30 to 35 years Annually
Pancreatic For patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols. Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family Annually
  Provide education about smoking cessation to reduce pancreatic cancer risk Individualized Individualized
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers. NA NA
Central Nervous System Physical/neurological examination 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA
Prostate Currently there are no specific medical management guidelines for prostate cancer risk in mutation carriers. However, the possibility of an increased risk for prostate cancer can be incorporated into the risk and benefit discussion about offering screening with digital rectal examination (DRE) and Prostate Specific Antigen (PSA). 45 years, or younger individualized
For Patients With A Cancer Diagnosis For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., antibodies to PD-1) NA NA

MSH2 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 70 52%-82% 1.8%
Endometrial To age 70 25%-60% 1.7%
Overall cancer risk (Lynch cancers) Risk for second Lynch-related cancer after a first cancer diagnosis Increased risk NA
Ovarian To age 70 4%-12% 0.7%
Gastric To age 70 6%-13% 0.4%
Small Bowel To age 70 3%-6% 0.1%
Urinary Tract To age 70 11%-21% 0.7%
Pancreatic To age 70 1%-6% 0.5%
Hepatobiliary Tract To age 70 1.4%-4% 0.5%
Central Nervous System To age 70 1%-3% 0.4%
Sebaceous Neoplasms To age 70 1%-9% <1.0%
Prostate To age 80 Up to 30% 10.9%

MSH2 Cancer Risk Management Table

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy 20 to 25 years, or 2 to 5 years younger than the earliest diagnosis in family if it is under age 25 Every 1 to 2 years
  Colorectal surgical evaluation may be appropriate for some patients Individualized NA
  Consider the use of aspirin as a risk reduction agent Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms. Individualized NA
  Consider pelvic examination, endometrial sampling and transvaginal ultrasound. 30 to 35 years Annually
  Consider hysterectomy. After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy. Age 40 or after completion of childbearing NA
  Consider transvaginal ultrasound and CA-125 measurement. 30 to 35 years NA
  Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives). Individualized NA
  Patient education about ovarian cancer symptoms Individualized NA
Gastric Consider testing and treating Helicobacter pylori infection. Individualized NA
  Consider upper endoscopy, particularly for patients with additional risk factors for gastric cancer, such as family history or Asian ancestry. Consider biopsy of the antrum. 30 to 40 years Every 2 to 5 years
Small Bowel Consider upper endoscopy, particularly for patients with additional risk factors for small bowel cancer, such as family history. 30 to 40 years Every 3 to 5 years
Urinary Tract Consider urinalysis. 30 to 35 years Annually
Pancreatic For patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols. Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family Annually
  Provide education about smoking cessation to reduce pancreatic cancer risk Individualized Individualized
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers. NA NA
Central Nervous System Physical/neurological examination 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA
Prostate Currently there are no specific medical management guidelines for prostate cancer risk in mutation carriers. However, the possibility of an increased risk for prostate cancer can be incorporated into the risk and benefit discussion about offering screening with digital rectal examination (DRE) and Prostate Specific Antigen (PSA). 45 years, or younger Individualized
For Patients With A Cancer Diagnosis For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., antibodies to PD-1) NA NA

MSH6 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal (male) To age 70 22%-69% 2.0%
Endometrial To age 70 16%-71% 1.7%
Overall cancer risk (Lynch cancers) Risk for second Lynch-related cancer after a first cancer diagnosis Increased risk NA
Colorectal (female) To age 70 10%-30% 1.5%
Ovarian To age 70 Elevated risk 0.7%
Gastric To age 70 Elevated risk 0.4%
Small Bowel To age 70 Elevated risk 0.1%
Urinary Tract To age 70 4%-7% 0.7%%
Pancreatic To age 70 Elevated risk 0.5%
Hepatobiliary Tract To age 70 Elevated risk 0.5%
Central Nervous System To age 70 Elevated risk 0.4%
Sebaceous Neoplasms To age 70 Elevated risk <1.0%
Prostate To age 80 Elevated risk 10.9%

MSH6 Cancer Risk Management Table

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy 25 to 30 years, or 2 to 5 years younger than the earliest diagnosis in family if it is under age 30 Every 1 to 2 years
  Colorectal surgical evaluation may be appropriate for some patients Individualized NA
  Consider the use of aspirin as a risk reduction agent Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms. Individualized NA
  Consider pelvic examination, endometrial sampling and transvaginal ultrasound. 30 to 35 years Annually
  Consider hysterectomy. After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy. Age 40 or after completion of childbearing NA
  Consider transvaginal ultrasound and CA-125 measurement. 30 to 35 years NA
  Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives). Individualized NA
  Patient education about ovarian cancer symptoms Individualized NA
Gastric Consider testing and treating Helicobacter pylori infection. Individualized NA
  Consider upper endoscopy, particularly for patients with additional risk factors for gastric cancer, such as family history or Asian ancestry. Consider biopsy of the antrum. 30 to 40 years Every 2 to 5 years
Small Bowel Consider upper endoscopy, particularly for patients with additional risk factors for small bowel cancer, such as family history. 30 to 40 years Every 3 to 5 years
Urinary Tract Consider urinalysis.Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family 30 to 35 years Annually
Pancreatic For patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols. Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family Annually
  Provide education about smoking cessation to reduce pancreatic cancer risk Individualized Individualized
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers. NA NA
Central Nervous System Physical/neurological examination 25-30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA
Prostate Currently there are no specific medical management guidelines for prostate cancer risk in mutation carriers. However, the possibility of an increased risk for prostate cancer can be incorporated into the risk and benefit discussion about offering screening with digital rectal examination (DRE) and Prostate Specific Antigen (PSA). 45 years, or younger Individualized
For Patients With A Cancer Diagnosis For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., antibodies to PD-1) NA NA

PMS2 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 70 Up to 20% 1.8%
Endometrial To age 70 Up to 15% 1.7%
Overall cancer risk (Lynch cancers) Risk for second Lynch-related cancer after a first cancer diagnosis Increased risk NA
Ovarian To age 70 Elevated risk 0.7%
Gastric To age 70 Elevated risk 0.4%
Small Bowel To age 70 Elevated risk 0.1%
Urinary Tract To age 70 Elevated risk 0.7%
Pancreatic To age 70 Elevated risk 0.5%
Hepatobiliary Tract To age 70 Elevated risk 0.5%
Central Nervous System To age 70 Elevated risk 0.4%
Sebaceous Neoplasms To age 70 Elevated risk <1.0%
Prostate To age 80 Elevated risk 10.9%

PMS2 Cancer Risk Management Table

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy 25 to 35 years, or 2 to 5 years younger than the earliest diagnosis in family if it is under age 30 Every 1 to 2 years
  Colorectal surgical evaluation may be appropriate for some patients Individualized NA
  Consider the use of aspirin as a risk reduction agent Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms. Individualized NA
  Consider pelvic examination, endometrial sampling and transvaginal ultrasound. 30 to 35 years Annually
  Consider hysterectomy. After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy. Age 40 or after completion of childbearing NA
  Consider transvaginal ultrasound and CA-125 measurement. 30 to 35 years NA
  Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives). Individualized NA
  Patient education about ovarian cancer symptoms Individualized NA
Gastric Consider testing and treating Helicobacter pylori infection. Individualized NA
  Consider upper endoscopy, particularly for patients with additional risk factors for gastric cancer, such as family history or Asian ancestry. Consider biopsy of the antrum 30 to 40 years Every 2 to 5 years
Small Bowel Consider upper endoscopy, particularly for patients with additional risk factors for small bowel cancer, such as family history. 30 to 40 years Every 3 to 5 years
Urinary Tract Consider urinalysis. 30 to 35 years Annually
Pancreatic For patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols. Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family Annually
  Provide education about smoking cessation to reduce pancreatic cancer risk Individualized Individualized
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers. NA NA
Central Nervous System Physical/neurological examination 25-30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA
Prostate Currently there are no specific medical management guidelines for prostate cancer risk in mutation carriers. However, the possibility of an increased risk for prostate cancer can be incorporated into the risk and benefit discussion about offering screening with digital rectal examination (DRE) and Prostate Specific Antigen (PSA). 45 years, or younger individualized
For Patients With A Cancer Diagnosis For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., antibodies to PD-1) NA NA

 

Recent Study from the Journal of Clinical Oncology Looking at PMS2

  • Cancer Risks for PMS2 – Associated Lynch Syndrome 
    • 284 families with 4,878 first and second degree family members
    • Colorectal cancer risk to age 80:   13% males  and  12% females

                                >> Gen pop risk:   males 6.6%   females 4.7%

    • Endometrial cancer risk to age 80:   13%

                                >> Gen pop risk:   2.4%

    • No clear evidence of increased risk:
      • OVARIAN, GASTRIC, HEPATOBILIARY, BLADDER, RENAL, BRAIN, BREAST, PROSTATE OR SMALL BOWEL

 

doi.org/10.1200/JCO.2018.78.477

Journal of Clinical Oncology 2018

EPCAM gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 70 52%-82% 1.8%
Endometrial To age 70 25%-60% 1.7%
Overall cancer risk (Lynch cancers) Risk for second Lynch-related cancer after a first cancer diagnosis Increased risk NA
Ovarian To age 70 4%-12% 0.7%
Gastric To age 70 6%-13% 0.4%
Small Bowel To age 70 3%-6% 0.1%
Urinary Tract To age 70 11%-21% 0.7%
Pancreatic To age 70 1%-6% 0.5%
Hepatobiliary Tract To age 70 1.4%-4% 0.5%
Central Nervous System To age 70 1%-3% 0.4%
Sebaceous Neoplasms To age 70 1%-9% <1.0%
Prostate To age 80 Uo to 30% 10.9%

EPCAM Cancer Risk Management Table

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy 20 to 25 years, or 2 to 5 years younger than the earliest diagnosis in family if it is under age 25 Every 1 to 2 years
  Colorectal surgical evaluation may be appropriate for some patients Individualized NA
  Consider the use of aspirin as a risk reduction agent Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms. Individualized NA
  Consider pelvic examination, endometrial sampling and transvaginal ultrasound. 30 to 35 years Annually
  Consider hysterectomy. After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy. Age 40 or after completion of childbearing NA
  Consider transvaginal ultrasound and CA-125 measurement. 30 to 35 years NA
  Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives). Individualized NA
  Patient education about ovarian cancer symptoms Individualized NA
Gastric Consider testing and treating for Helicobacter pylori infection. Individualized NA
  Consider upper endoscopy, particularly for patients with additional risk factors for gastric cancer, such as family history or Asian ancestry. Consider biopsy of the antrum. 30 to 40 years Every 2 to 5 years
Small Bowel Consider upper endoscopy, particularly for patients with additional risk factors for small bowel cancer, such as family history. 30 to 40 years Every 3 to 5 years
Urinary Tract Consider urinalysis. 30 to 35 years Annually
Pancreatic
For patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols. Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family Annually
  Provide education about smoking cessation to reduce pancreatic cancer risk Individualized Individualized
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers. NA NA
Central Nervous System Physical/neurological examination 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA
Prostate Currently there are no specific medical management guidelines for prostate cancer risk in mutation carriers. However, the possibility of an increased risk for prostate cancer can be incorporated into the risk and benefit discussion about offering screening with digital rectal examination (DRE) and Prostate Specific Antigen (PSA) 45 years, or younger individualized
For Patients With A Cancer Diagnosis For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., antibodies to PD-1) NA NA

Associated Syndrome

Associated Syndrome

Associated Syndrome

Associated Syndrome

Unique Challenges

Unique Challenges

Unique Challenges

Unique Challenges

Unique Challenges