Familial Colorectal Cancers: Hereditary Non-Polyposis Colon Cancer (HNPCC)/Lynch Syndrome

Author: Christina Bach, LCSW, MBE, OSW-C, FAOSW
Content Contributor: Karen Arnold-Korzeniowski, MSN RN
Last Reviewed: June 01, 2023

About 153,000 people are diagnosed with colorectal cancer each year in the United States. About 10 to 15% of these cancers may be caused by genetic abnormalities that run in families. One of these abnormalities is Lynch Syndrome (HNPCC). It is the most common type of hereditary colorectal cancer and causes about 3% of colorectal cancer diagnoses.

There are two types of Lynch syndrome: Type I (HNPCC type A) and Type II (HNPCC type B).

  • Families with Lynch type I often report many cases of colorectal cancers in young (under age 50) relatives. The average age of diagnosis of colon cancer in patients with this syndrome is 44 years old as compared to 68 (for men) and 72 (for women) years old in people without a genetic syndrome (sometimes called a sporadic cancer).
  • Families with a history of Lynch Type II syndrome also report colorectal cancers in young relatives. They also have cases of HNPCC-related cancers, such as endometrial, gastric, liver, kidney, brain, and some skin cancers.

Criteria for HNPCC

The genes that have been found to cause HNPCC are MLH1, MSH2, MSH6, PMS2, and EPCAM. Someone with a mutation (change) on any one of these genes has about an 80% risk of colon cancer during his or her life.

People with HNPCC are most likely to have cancer on the right side of the colon. Sporadic cases (those not caused by a gene mutation) tend to cause cancer on the left side of the colon. Flexible sigmoidoscopy, a standard screening test for colorectal cancer, only looks at the left side of the colon and is a poor screening test for those with HNPCC.

Those with HNPCC develop polyps at the same rate as other people but the polyps are more likely to turn into cancer. The progression of polyps to cancer when you have HNPCC is quicker than sporadic cases of colorectal cancer.

The Amsterdam II criteria helps figure out if a family has a risk of HPNCC. These criteria state that HPNCC should be suspected in families when at least 3 relatives have an HNPCC-related cancer and:

  • One is a first-degree relative (parent, sibling, or child) of the other two.
  • At least 2 successive (2 in a row) generations are affected.
  • At least 1 of these family members is diagnosed with cancer before age 50.
  • FAP (Familial adenomatous polyposis) must be ruled out.
  • The tumors are verified by pathology (samples looked at under a microscope).

Genetic Testing

Families that meet the Amsterdam II criteria may want to have genetic testing done. If a family member is positive for a genetic abnormality, other family members at risk can then be tested and given guidance regarding cancer screening.

It is important to remember that a negative result is not always helpful. This could mean that there is no genetic mutation causing this cancer or increasing this family’s cancer risk. However, it could also mean that the test was not able to detect a mutation - even though one exists. This could happen if the family carries a mutation in a gene that has not yet been discovered or a mutation for which testing has not yet been developed.

Genetic testing is something that should not be taken lightly. The results of the test might not only affect you but also your family members. Some concerns might be access to testing, lack of preventive options, passing the gene on to one's children, and discrimination in employment and insurance matters.

A genetic counselor should meet with anyone who is thinking about genetic testing. They are trained to help patients understand genetic testing and results and can help you make the right decision for you and your family.

Cancer Screening in HNPCC

People with HNPCC tend to develop cancers earlier and should start being screened for cancer at a younger age. Many organizations have published guidelines on cancer screening for people with HNPCC mutations, including the American College of Gastroenterology, the United States Multi-Society Task Force on Colorectal Cancer, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. The following are some recommendations from these groups.:

  • Have colorectal cancer screening with colonoscopy every 1-2 years beginning between ages 20 to 25 years, or 2-5 years before the earliest age of colorectal cancer diagnosis age in the family – whichever comes first.
  • Screening for gastric cancer can be done with upper endoscopy starting between ages 30-35 years. If H. Pylori is found, it should be treated. The test should be repeated every 3 to 5 years.
  • Have a yearly skin exam to look for skin cancers that have been linked to Lynch Syndrome.
  • Mutation carriers who have had one or more first-degree relatives with pancreatic cancer may benefit from screening for pancreatic cancer.
  • Women should have an annual pelvic exam, pelvic ultrasound, and endometrial biopsy from ages 30-35.

Talk to your provider and genetic counselor about what screening tests are right for you and at what age you should start them.

Researchers have learned a great deal about genetic syndromes in the past 20 years with the help of patients becoming involved in research studies. If you have a family history of cancer and would like to learn more about cancer risk and research, check out the links below.

Resources for More Information

For general Lynch Syndrome (HPNCC) information visit, Lynch Syndrome International.

Find a genetic counselor in your area.

Learn more about cancer family registries.

Learn more about screening through the Lynch Syndrome Screening Network.

American Society of Clinical Oncology. Lynch Syndrome. 2021.

Centers for Disease Control. Lynch Syndrome. 2022.

Giardiello, F. M., Allen, J. I., Axilbund, J. E., Boland, C. R., Burke, C. A., Burt, R. W., ... & Levin, T. R. (2014). Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology, 147(2), 502-526.

Kravochuck, S. E., Kalady, M. F., Burke, C. A., Heald, B., & Church, J. M. (2014). Defining HNPCC and Lynch syndrome: what's in a name? Gut, 63(9), 1525-1526.

Lynch, H. T., Snyder, C. L., Shaw, T. G., Heinen, C. D., & Hitchins, M. P. (2015). Milestones of Lynch syndrome: 1895-2015. Nature Reviews Cancer, 15(3), 181-194.

National Institute of Health (NIH): Genetics Home Reference. Lynch Syndrome. (2019). Retrieved from https://ghr.nlm.nih.gov/condition/lynch-syndrome#statistics

Provenzale D, Gupta S, et al. NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2019, National Comprehensive Cancer Network.

Rubenstein, J. H., Enns, R., Heidelbaugh, J., Barkun, A., Adams, M. A., Dorn, S. D., ... & Kosinski, L. R. (2015). American Gastroenterological Association Institute guideline on the diagnosis and management of Lynch syndrome. Gastroenterology, 149(3), 777-782.

Stoffel, E. M., Mangu, P. B., Gruber, S. B., Hamilton, S. R., Kalady, M. F., Lau, M. W. Y., ... & Limburg, P. J. (2015). Hereditary colorectal cancer syndromes: American society of clinical oncology clinical practice guideline endorsement of the familial risk–colorectal cancer: European society for medical oncology clinical practice guidelines. Journal of clinical oncology, 33(2), 209.

Syngal, S., Brand, R. E., Church, J. M., Giardiello, F. M., Hampel, H. L., & Burt, R. W. (2015). ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. The American journal of gastroenterology, 110(2), 223.

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