Lynch syndrome (LS)

MLH1, MSH2, MSH6, PMS2, AND EPCAM ASSOCIATED CANCER RISKS

 BREASTOVARIANGASTRICCOLORECTALPANCREATICMELANOMAPROSTATEENDOMETRIALOTHER

Additional Information

Associated Syndrome Name: Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

MLH1 Summary Cancer Risk Table

CANCER GENETIC CANCER RISK
Colorectal High Risk
Endometrial High Risk
Gastric High Risk
Ovarian High Risk
Pancreatic Elevated Risk
Other High Risk

MLH1 gene Overview

Lynch syndrome 1, 2, 3, 4, 5, 6, 7, 8

  • Individuals with mutations in MLH1 have a condition called Lynch syndrome. This condition is also known as Hereditary Non-Polyposis Colon Cancer (HNPCC).
  • Men and women with Lynch syndrome due to mutations in MLH1 have a high risk of developing colorectal cancer, often at young ages. Colorectal cancer in patients with Lynch syndrome develops from adenomatous polyps which progress to cancer more quickly than polyps in individuals who do not have Lynch syndrome.
  • Women with Lynch syndrome due to mutations in MLH1 have a high risk for developing endometrial and ovarian cancer, often at young ages.
  • Patients with Lynch syndrome due to mutations in MLH1 also have an increased risk of developing a wide variety of other cancers, including gastric, small bowel, urinary tract, hepatobiliary tract, brain (usually glioblastoma), sebaceous gland, and pancreatic.
  • Studies have investigated the possibility that patients with Lynch syndrome have an increased risk for other cancers, including breast cancer, prostate cancer, and adrenocortical carcinoma. However, the data are not conclusive at this time and there are currently no medical management guidelines related to these cancers.
  • Patients with Lynch syndrome have a high risk for developing second primary cancers following an initial diagnosis of colorectal or endometrial cancer. This includes a high risk for endometrial cancer in women following colorectal cancer and vice versa, a high risk for a second primary colorectal cancer in any portions of the colon or rectum remaining after surgical treatment, and a high risk for other Lynch associated cancers, such as those of the upper gastrointestinal tract, urinary tract, and other sites.
  • Although there are high risks for cancer in patients with Lynch syndrome, many of these risks can be greatly reduced with appropriate medical management. Guidelines for the medical management of patients with Lynch syndrome have been developed by the National Comprehensive Cancer Network (NCCN) and other expert groups. These are listed below. It is recommended that patients with an MLH1 mutation and a diagnosis of Lynch syndrome be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with this condition.

MLH1 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 701, 6 52%-82% 1.9%
Endometrial To age 701, 6 25%-60% 1.6%
Overall cancer risk (Lynch cancers) Risk for a second Lynch-related cancer after a first cancer diagnosis10, 11 Increased risk NA
Ovarian To age 701, 6 4%-12% 0.7%
Gastric To age 701, 6 6%-13% 0.3%
Small Bowel To age 701, 6 3%-6% 0.1%
Urinary Tract To age 701, 6, 8 1%-7% <1.0%
Pancreatic To age 701, 2, 6 1%-6% 0.5%
Hepatobiliary Tract To age 701, 6 1.4%-4% 0.4%
Central Nervous System To age 701, 6 1%-3% 0.4%
Sebaceous Neoplasms To age 701, 6 1%-9% <1.0%

MLH1 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy6, 7 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 patients6 Individualized NA
Consider the use of aspirin as a risk-reduction agent6, 7 Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms.6 Individualized NA
Consider pelvic examination, endometrial sampling and transvaginal ultrasound.6, 7 30 to 35 years Annually
Consider hysterectomy.6, 7 After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy.6, 7 Age 40 or after completion of childbearing NA
Consider transvaginal ultrasound and CA-125 measurement.6, 7 30 to 35 years NA
Gastric Treat for Helicobacter pylori infection if present.7 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.6, 7, 12 30 to 35 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.6, 7 30 to 35 years Every 3 to 5 years
Urinary Tract Consider urinalysis.6, 7 30 to 35 years Annually
Pancreatic 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.13 Individualized NA
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers.6 NA NA
Central Nervous System Physical/neurological examination6 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the MLH1 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

In rare instances, an individual may inherit mutations in both copies of the MLH1 gene, leading to the condition Constitutional Mismatch Repair-Deficiency syndrome (CMMR-D). Individuals with CMMR-D often have significant complications in childhood, including colorectal polyposis and a high risk for colorectal, small bowel, brain, and hematologic cancers. Individuals with CMMR-D often have café-au-lait spots. The children of this patient are at risk of inheriting CMMR-D only if the other parent is also a carrier of a MLH1 mutation. Screening the spouse/partner of this patient for MLH1 mutations may be appropriate.1

References

  1. Kohlmann W, Gruber SB. Lynch Syndrome. 2014 May 22. In:Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK1211/ PMID: 20301390.
  2. Kastrinos F, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009 302:1790-5. PMID: 19861671.
  3. Lin KM, et al. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum. 1998 41:428-33. PMID: 9559626.
  4. Win AK, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013 105:274-9. PMID: 23385444.
  5. Win AK, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012 104:1363-72. PMID: 22933731.
  6. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at http://www.nccn.org.
  7. Giardiello FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2014 109:1159-79. PMID: 25070057.
  8. Joost P, et al. Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations. Urology. 2015 86:1212-7. PMID: 26385421.
  9. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  10. Larsen Haidle J, Howe JR. Juvenile Polyposis Syndrome. 2015 Dec 3. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642.
  11. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Colorectal Cancer Screening. V 2.2016. October 20. Available at http://www.nccn.org.
  12. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at http://www.nccn.org.
  13. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
Last Updated on 01-Jun-2017

Associated Syndrome Name: Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

MSH2 Summary Cancer Risk Table

CANCER GENETIC CANCER RISK
Colorectal High Risk
Endometrial High Risk
Gastric High Risk
Ovarian High Risk
Pancreatic Elevated Risk
Other High Risk

MSH2 gene Overview

Lynch syndrome 1, 2, 3, 4, 5, 6, 7, 8

  • Individuals with mutations in MSH2 have a condition called Lynch syndrome. This condition is also known as Hereditary Non-Polyposis Colon Cancer (HNPCC).
  • Men and women with Lynch syndrome due to mutations in MSH2 have a high risk of developing colorectal cancer, often at young ages. Colorectal cancer in patients with Lynch syndrome develops from adenomatous polyps which progress to cancer more quickly than polyps in individuals who do not have Lynch syndrome.
  • Women with Lynch syndrome due to mutations in MSH2 have a high risk for developing endometrial and ovarian cancer, often at young ages.
  • Patients with Lynch syndrome due to mutations in MSH2 also have an increased risk of developing a wide variety of other cancers, including gastric, small bowel, urinary tract, hepatobiliary tract, brain (usually glioblastoma), sebaceous gland, and pancreatic.
  • Studies have investigated the possibility that patients with Lynch syndrome have an increased risk for other cancers, including breast cancer, prostate cancer, and adrenocortical carcinoma. However, the data are not conclusive at this time and there are currently no medical management guidelines related to these cancers.
  • Patients with Lynch syndrome have a high risk for developing second primary cancers following an initial diagnosis of colorectal or endometrial cancer. This includes a high risk for endometrial cancer in women following colorectal cancer and vice versa, a high risk for a second primary colorectal cancer in any portions of the colon or rectum remaining after surgical treatment, and a high risk for other Lynch associated cancers, such as those of the upper gastrointestinal tract, urinary tract, and other sites.
  • Although there are high risks for cancer in patients with Lynch syndrome, many of these risks can be greatly reduced with appropriate medical management. Guidelines for the medical management of patients with Lynch syndrome have been developed by the National Comprehensive Cancer Network (NCCN) and other expert groups. These are listed below. It is recommended that patients with an MSH2 mutation and a diagnosis of Lynch syndrome be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with this condition.

MSH2 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 701, 6 52%-82% 1.9%
Endometrial To age 701, 6 25%-60% 1.6%
Overall cancer risk (Lynch cancers) Risk for a second Lynch-related cancer after a first cancer diagnosis10, 11 Increased risk NA
Ovarian To age 701, 6 4%-12% 0.7%
Gastric To age 701, 6 6%-13% 0.3%
Small Bowel To age 701, 6 3%-6% 0.1%
Urinary Tract To age 701, 6, 8 1%-7%, or higher <1.0%
Pancreatic To age 701, 2, 6 1%-6% 0.5%
Hepatobiliary Tract To age 701, 6 1.4%-4% 0.4%
Central Nervous System To age 701, 6 1%-3% 0.4%
Sebaceous Neoplasms To age 701, 6 1%-9% <1.0%

MSH2 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy6, 7 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 patients6 Individualized NA
Consider the use of aspirin as a risk-reduction agent6, 7 Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms.6 Individualized NA
Consider pelvic examination, endometrial sampling and transvaginal ultrasound.6, 7 30 to 35 years Annually
Consider hysterectomy.6, 7 After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy.6, 7 Age 40 or after completion of childbearing NA
Consider transvaginal ultrasound and CA-125 measurement.6, 7 30 to 35 years NA
Gastric Treat for Helicobacter pylori infection if present.7 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.6, 7, 12 30 to 35 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.6, 7 30 to 35 years Every 3 to 5 years
Urinary Tract Consider urinalysis.6, 7 30 to 35 years Annually
Pancreatic 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.13 Individualized NA
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers.6 NA NA
Central Nervous System Physical/neurological examination6 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the MSH2 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

In rare instances, an individual may inherit mutations in both copies of the MSH2 gene, leading to the condition Constitutional Mismatch Repair-Deficiency syndrome (CMMR-D). Individuals with CMMR-D often have significant complications in childhood, including colorectal polyposis and a high risk for colorectal, small bowel, brain, and hematologic cancers. Individuals with CMMR-D often have café-au-lait spots. The children of this patient are at risk of inheriting CMMR-D only if the other parent is also a carrier of a MSH2 mutation. Screening the spouse/partner of this patient for MSH2 mutations may be appropriate.1

References

  1. Kohlmann W, Gruber SB. Lynch Syndrome. 2014 May 22. In:Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK1211/ PMID: 20301390.
  2. Kastrinos F, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009 302:1790-5. PMID: 19861671.
  3. Lin KM, et al. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum. 1998 41:428-33. PMID: 9559626.
  4. Win AK, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013 105:274-9. PMID: 23385444.
  5. Win AK, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012 104:1363-72. PMID: 22933731.
  6. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at http://www.nccn.org.
  7. Giardiello FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2014 109:1159-79. PMID: 25070057.
  8. Joost P, et al. Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations. Urology. 2015 86:1212-7. PMID: 26385421.
  9. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  10. Larsen Haidle J, Howe JR. Juvenile Polyposis Syndrome. 2015 Dec 3. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642.
  11. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Colorectal Cancer Screening. V 2.2016. October 20. Available at http://www.nccn.org.
  12. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at http://www.nccn.org.
  13. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
Last Updated on 01-Jun-2017

Associated Syndrome Name: Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

MSH6 Summary Cancer Risk Table

CANCER GENETIC CANCER RISK
Colorectal High Risk
Endometrial High Risk
Pancreatic Elevated Risk
Gastric Elevated Risk
Ovarian Elevated Risk
Other High Risk

MSH6 gene Overview

Lynch syndrome 1, 2, 3, 4, 5, 6, 7, 8, 9

  • Individuals with mutations in MSH6 have a condition called Lynch syndrome. This condition is also known as Hereditary Non-Polyposis Colon Cancer (HNPCC).
  • Men and women with Lynch syndrome due to mutations in MSH6 have a high risk of developing colorectal cancer, often at younger ages than seen in the general population. Colorectal cancer in patients with Lynch syndrome develops from adenomatous polyps which progress to cancer more quickly than polyps in individuals who do not have Lynch syndrome. Colorectal cancer risk may be somewhat lower in women than in men, but there are no differences in the colorectal cancer screening guidelines for men and women.
  • Women with Lynch syndrome due to mutations in MSH6 have a high risk for developing endometrial cancer and an elevated risk for ovarian cancer, often at younger ages than typical in the general population.
  • Patients with Lynch syndrome due to mutations in MSH6 are also believed to have an increased risk of developing a wide variety of other Lynch syndrome associated cancers, including gastric, small bowel, urinary tract, hepatobiliary tract, brain (usually glioblastoma), sebaceous gland, and pancreatic. Precise risk estimates are not available because there is less information available for patients with MSH6 mutations compared with patients who have mutations in other Lynch syndrome genes. Although specific screening and prevention recommendations are not provided for some of these cancer risks in MSH6 mutation carriers, it may be appropriate to consider available options for select patients, such as those with a family history of any of these cancers.
  • Studies have investigated the possibility that patients with Lynch syndrome have an increased risk for other cancers, including breast cancer, prostate cancer, and adrenocortical carcinoma. However, the data are not conclusive at this time and there are currently no medical management guidelines related to these cancers.
  • Patients with Lynch syndrome have a high risk for developing second primary cancers following an initial diagnosis of colorectal or endometrial cancer. This includes a high risk for endometrial cancer in women following colorectal cancer and vice versa, a high risk for a second primary colorectal cancer in any portions of the colon or rectum remaining after surgical treatment, and an increased risk for other Lynch associated cancers, such as those of the upper gastrointestinal tract, urinary tract, and other sites.
  • Although there are high risks for cancer in patients with Lynch syndrome, many of these risks can be greatly reduced with appropriate medical management. Guidelines for the medical management of patients with Lynch syndrome have been developed by the National Comprehensive Cancer Network (NCCN) and other expert groups. These are listed below. It is recommended that patients with an MSH6 mutation and a diagnosis of Lynch syndrome be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with this condition.

MSH6 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal (male) To age 704, 5, 6 22%-69% 2.2%
Endometrial To age 704, 5, 6 16%-71% 1.6%
Overall cancer risk (Lynch cancers) Risk for a second Lynch-related cancer after a first cancer diagnosis11, 12 Increased risk NA
Colorectal (female) To age 704, 5, 6 10%-30% 1.7%
Ovarian To age 701, 4, 5, 6, 8 Elevated risk 0.7%
Gastric To age 701, 4, 5, 6, 8 Elevated risk 0.3%
Small Bowel To age 701, 4, 5, 6, 8 Elevated risk 0.1%
Urinary Tract To age 701, 4, 5, 6, 8 Elevated risk <1.0%
Pancreatic To age 708, 13, 14 Elevated risk 0.5%
Hepatobiliary Tract To age 701, 4, 5, 6, 8 Elevated risk 0.4%
Central Nervous System To age 701, 4, 5, 6, 8 Elevated risk 0.4%
Sebaceous Neoplasms To age 701, 4, 5, 6, 8 Elevated risk <1.0%

MSH6 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy8, 9 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 patients8 Individualized NA
Consider the use of aspirin as a risk-reduction agent8, 9 Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms.8 Individualized NA
Consider pelvic examination, endometrial sampling and transvaginal ultrasound.8, 9 30 to 35 years Annually
Consider hysterectomy.8, 9 After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy.8, 9 Age 40 or after completion of childbearing NA
Consider transvaginal ultrasound and CA-125 measurement.8, 9 30 to 35 years NA
Gastric Treat for Helicobacter pylori infection if present.9 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.8, 9, 15 30 to 35 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.8, 9 30 to 35 years Every 3 to 5 years
Urinary Tract Consider urinalysis.8, 9 30 to 35 years Annually
Pancreatic 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.13 Individualized NA
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers.8 NA NA
Central Nervous System Physical/neurological examination8 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the MSH6 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

In rare instances, an individual may inherit mutations in both copies of the MSH6 gene, leading to the condition Constitutional Mismatch Repair-Deficiency syndrome (CMMR-D). Individuals with CMMR-D often have significant complications in childhood, including colorectal polyposis and a high risk for colorectal, small bowel, brain, and hematologic cancers. Individuals with CMMR-D often have café-au-lait spots. The children of this patient are at risk of inheriting CMMR-D only if the other parent is also a carrier of a MSH6 mutation. Screening the spouse/partner of this patient for MSH6 mutations may be appropriate.1

References

  1. Kohlmann W, Gruber SB. Lynch Syndrome. 2014 May 22. In:Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK1211/ PMID: 20301390.
  2. Lin KM, et al. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum. 1998 41:428-33. PMID: 9559626.
  3. Win AK, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013 105:274-9. PMID: 23385444.
  4. Hendriks YM, et al. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology. 2004 127:17-25. PMID: 15236168.
  5. Bonadona V, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011 305:2304-10. PMID: 21642682.
  6. Baglietto L, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010 102:193-201. PMID: 20028993.
  7. Win AK, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012 104:1363-72. PMID: 22933731.
  8. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at http://www.nccn.org.
  9. Giardiello FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2014 109:1159-79. PMID: 25070057.
  10. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  11. Larsen Haidle J, Howe JR. Juvenile Polyposis Syndrome. 2015 Dec 3. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642.
  12. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Colorectal Cancer Screening. V 2.2016. October 20. Available at http://www.nccn.org.
  13. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
  14. Kastrinos F, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009 302:1790-5. PMID: 19861671.
  15. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at http://www.nccn.org.
Last Updated on 01-Jun-2017

Associated Syndrome Name: Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

PMS2 Summary Cancer Risk Table

CANCER GENETIC CANCER RISK
Colorectal High Risk
Endometrial High Risk
Pancreatic Elevated Risk
Gastric Elevated Risk
Ovarian Elevated Risk
Other High Risk

PMS2 gene Overview

Lynch syndrome 1, 2, 3, 4, 5, 6, 7, 8

  • Individuals with mutations in PMS2 have a condition called Lynch syndrome. This condition is also known as Hereditary Non-Polyposis Colon Cancer (HNPCC).
  • Men and women with Lynch syndrome due to mutations in PMS2 have a high risk of developing colorectal cancer, often at younger ages than seen in the general population. Colorectal cancer in patients with Lynch syndrome develops from adenomatous polyps which progress to cancer more quickly than polyps in individuals who do not have Lynch syndrome.
  • Women with Lynch syndrome due to mutations in PMS2 have a high risk for developing endometrial cancer and possibly an elevated risk for ovarian cancer, often at younger ages than typical in the general population.
  • Patients with Lynch syndrome due to mutations in PMS2 are also believed to have an increased risk of developing a wide variety of other Lynch syndrome associated cancers, including gastric, small bowel, urinary tract, hepatobiliary tract, brain (usually glioblastoma), sebaceous gland, and pancreatic. Precise risk estimates are not available because there is less information available for patients with PMS2 mutations compared with patients who have mutations in other Lynch syndrome genes. Although specific screening and prevention recommendations are not provided for some of these cancer risks in PMS2 mutation carriers, it may be appropriate to consider available options for select patients, such as those with a family history of any of these cancers.
  • Studies have investigated the possibility that patients with Lynch syndrome have an increased risk for other cancers, including breast cancer, prostate cancer, and adrenocortical carcinoma. However, the data are not conclusive at this time and there are currently no medical management guidelines related to these cancers.
  • Patients with Lynch syndrome have a high risk for developing second primary cancers following an initial diagnosis of colorectal or endometrial cancer. This includes a high risk for endometrial cancer in women following colorectal cancer and vice versa, a high risk for a second primary colorectal cancer in any portions of the colon or rectum remaining after surgical treatment, and a high risk for other Lynch associated cancers, such as those of the upper gastrointestinal tract, urinary tract, and other sites.
  • Although there are high risks for cancer in patients with Lynch syndrome, many of these risks can be greatly reduced with appropriate medical management. Guidelines for the medical management of patients with Lynch syndrome have been developed by the National Comprehensive Cancer Network (NCCN) and other expert groups. These are listed below. It is recommended that patients with a PMS2 mutation and a diagnosis of Lynch syndrome be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with this condition.

PMS2 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 702, 10 Up to 20% 1.9%
Endometrial To age 702, 10 Up to 15% 1.6%
Overall cancer risk (Lynch cancers) Risk for a second Lynch-related cancer after a first cancer diagnosis11, 12 Increased risk NA
Ovarian To age 701, 2, 7, 10 Elevated risk 0.7%
Gastric To age 701, 2, 7, 10 Elevated risk 0.3%
Small Bowel To age 701, 2, 7, 10 Elevated risk 0.1%
Urinary Tract To age 701, 2, 7, 10 Elevated risk <1.0%
Pancreatic To age 701, 2, 3, 7, 10, 13 Elevated risk 0.5%
Hepatobiliary Tract To age 701, 2, 7, 10 Elevated risk 0.4%
Central Nervous System To age 701, 2, 7, 10 Elevated risk 0.4%
Sebaceous Neoplasms To age 701, 2, 7, 10 Elevated risk <1.0%

PMS2 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy7, 8 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 patients7 Individualized NA
Consider the use of aspirin as a risk-reduction agent7, 8 Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms.7 Individualized NA
Consider pelvic examination, endometrial sampling and transvaginal ultrasound.7, 8 30 to 35 years Annually
Consider hysterectomy.7, 8 After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy.7, 8 Age 40 or after completion of childbearing NA
Consider transvaginal ultrasound and CA-125 measurement.7, 8 30 to 35 years NA
Gastric Treat for Helicobacter pylori infection if present.8 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.7, 8, 14 30 to 35 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.7, 8 30 to 35 years Every 3 to 5 years
Urinary Tract Consider urinalysis.7, 8 30 to 35 years Annually
Pancreatic 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.13 Individualized NA
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers.7 NA NA
Central Nervous System Physical/neurological examination7 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the PMS2 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

In rare instances, an individual may inherit mutations in both copies of the PMS2 gene, leading to the condition Constitutional Mismatch Repair-Deficiency syndrome (CMMR-D). Individuals with CMMR-D often have significant complications in childhood, including colorectal polyposis and a high risk for colorectal, small bowel, brain, and hematologic cancers. Individuals with CMMR-D often have café-au-lait spots. The children of this patient are at risk of inheriting CMMR-D only if the other parent is also a carrier of a PMS2 mutation. Screening the spouse/partner of this patient for PMS2 mutations may be appropriate.1

References

  1. Kohlmann W, Gruber SB. Lynch Syndrome. 2014 May 22. In:Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK1211/ PMID: 20301390.
  2. Senter L, et al. The clinical phenotype of Lynch syndrome due to germline PMS2 mutations. Gastroenterology. 2008 135419-28. PMID: 18602922.
  3. Kastrinos F, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009 302:1790-5. PMID: 19861671.
  4. Lin KM, et al. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum. 1998 41:428-33. PMID: 9559626.
  5. Win AK, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013 105:274-9. PMID: 23385444.
  6. Win AK, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012 104:1363-72. PMID: 22933731.
  7. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at http://www.nccn.org.
  8. Giardiello FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2014 109:1159-79. PMID: 25070057.
  9. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  10. ten Broeke SW, et al. Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk. J Clin Oncol. 2015 33:319-25. PMID: 25512458.
  11. Larsen Haidle J, Howe JR. Juvenile Polyposis Syndrome. 2015 Dec 3. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642.
  12. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Colorectal Cancer Screening. V 2.2016. October 20. Available at http://www.nccn.org.
  13. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
  14. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at http://www.nccn.org.
Last Updated on 01-Jun-2017

Associated Syndrome Name: Lynch syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

EPCAM Summary Cancer Risk Table

CANCER GENETIC CANCER RISK
Colorectal High Risk
Endometrial High Risk
Gastric High Risk
Ovarian High Risk
Pancreatic Elevated Risk
Other High Risk

EPCAM gene Overview

Lynch syndrome 1, 2, 3, 4, 5, 6, 7, 8, 9

  • Individuals with mutations in EPCAM have a condition called Lynch syndrome. This condition is also known as Hereditary Non-Polyposis Colon Cancer (HNPCC).
  • Men and women with Lynch syndrome due to mutations in EPCAM have a high risk of developing colorectal cancer, often at young ages. Colorectal cancer in patients with Lynch syndrome develops from adenomatous polyps which progress to cancer more quickly than polyps in individuals who do not have Lynch syndrome.
  • Women with Lynch syndrome due to mutations in EPCAM have a high risk for developing endometrial and ovarian cancer, often at young ages.
  • Patients with Lynch syndrome due to mutations in EPCAM are also believed to have an increased risk of developing a wide variety of other cancers, including gastric, small bowel, urinary tract, hepatobiliary tract, brain (usually glioblastoma), sebaceous gland, and pancreatic.
  • Studies have investigated the possibility that patients with Lynch syndrome have an increased risk for other cancers, including breast cancer, prostate cancer, and adrenocortical carcinoma. However, the data are not conclusive at this time and there are currently no medical management guidelines related to these cancers.
  • Patients with Lynch syndrome have a high risk for developing second primary cancers following an initial diagnosis of colorectal or endometrial cancer. This includes a high risk for endometrial cancer in women following colorectal cancer and vice versa, a high risk for a second primary colorectal cancer in any portions of the colon or rectum remaining after surgical treatment, and a high risk for other Lynch associated cancers, such as those of the upper gastrointestinal tract, urinary tract, and other sites.
  • Cancer risks for patients with Lynch syndrome due to mutations in EPCAM are currently estimated to be similar to those for patients with Lynch syndrome due to mutations in MSH2, and medical management guidelines are currently the same for patients with mutations in either gene. However, it is possible that this will change over time as we learn more about the exact risks associated with mutations in EPCAM. There are some early indications that endometrial cancer risk may be much lower for women with certain types of mutations in EPCAM.
  • Although there are high risks for cancer in patients with Lynch syndrome, many of these risks can be greatly reduced with appropriate medical management. Guidelines for the medical management of patients with Lynch syndrome have been developed by the National Comprehensive Cancer Network (NCCN) and other expert groups. These are listed below. It is recommended that patients with an EPCAM mutation and a diagnosis of Lynch syndrome be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with this condition.

EPCAM gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 701, 7 52%-82% 1.9%
Endometrial To age 701, 7 25%-60% 1.6%
Overall cancer risk (Lynch cancers) Risk for a second Lynch-related cancer after a first cancer diagnosis11, 12 Increased risk NA
Ovarian To age 701, 7 4%-12% 0.7%
Gastric To age 701, 7 6%-13% 0.3%
Small Bowel To age 701, 7 3%-6% 0.1%
Urinary Tract To age 701, 7, 9 1%-7%, or higher <1.0%
Pancreatic To age 701, 2, 7 1%-6% 0.5%
Hepatobiliary Tract To age 701, 7 1.4%-4% 0.4%
Central Nervous System To age 701, 7 1%-3% 0.4%
Sebaceous Neoplasms To age 701, 7 1%-9% <1.0%

EPCAM Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy7, 8 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 patients7 Individualized NA
Consider the use of aspirin as a risk-reduction agent7, 8 Individualized Individualized
Endometrial Patient education about endometrial cancer symptoms.7 Individualized NA
Consider pelvic examination, endometrial sampling and transvaginal ultrasound.7, 8 30 to 35 years Annually
Consider hysterectomy.7, 8 After completion of childbearing NA
Ovarian Consider bilateral salpingo-oophorectomy.7, 8 Age 40 or after completion of childbearing NA
Consider transvaginal ultrasound and CA-125 measurement.7, 8 30 to 35 years NA
Gastric Treat for Helicobacter pylori infection if present.8 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.7, 8, 13 30 to 35 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.7, 8 30 to 35 years Every 3 to 5 years
Urinary Tract Consider urinalysis.7, 8 30 to 35 years Annually
Pancreatic 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.14 Individualized NA
Hepatobiliary Tract Currently there are no specific medical management guidelines for hepatobiliary cancer risk in mutation carriers.7 NA NA
Central Nervous System Physical/neurological examination7 25 to 30 years Annually
Sebaceous Neoplasms Currently there are no specific medical management guidelines for sebaceous neoplasm risk in mutation carriers. NA NA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the EPCAM gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

References

  1. Kohlmann W, Gruber SB. Lynch Syndrome. 2014 May 22. In:Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK1211/ PMID: 20301390.
  2. Kastrinos F, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009 302:1790-5. PMID: 19861671.
  3. Lin KM, et al. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum. 1998 41:428-33. PMID: 9559626.
  4. Win AK, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013 105:274-9. PMID: 23385444.
  5. Win AK, et al. Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. J Natl Cancer Inst. 2012 104:1363-72. PMID: 22933731.
  6. Kempers MJ, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet. Oncol. 2011 12:49-55. PMID: 21145788.
  7. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at http://www.nccn.org.
  8. Giardiello FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2014 109:1159-79. PMID: 25070057.
  9. Joost P, et al. Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations. Urology. 2015 86:1212-7. PMID: 26385421.
  10. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  11. Larsen Haidle J, Howe JR. Juvenile Polyposis Syndrome. 2015 Dec 3. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1469/ PMID: 20301642.
  12. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Colorectal Cancer Screening. V 2.2016. October 20. Available at http://www.nccn.org.
  13. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at http://www.nccn.org.
  14. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
Last Updated on 01-Jun-2017