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Lynch syndrome, the most common hereditary cancer disorder, runs in families in an autosomal dominant inheritance with germline pathogenic alterations in DNA mismatch repair (MMR) genes, the function of which is to maintain DNA genetic stability. The inability of these genes to repair DNA is what leads to the development of cancer. 

Roughly 3% to 5% of all colorectal cancers are thought to result from Lynch syndrome and individuals with a Lynch syndrome gene mutation are 20 times more likely to develop colorectal cancer and several other cancers including endometrial, ovarian pancreatic, prostate and gastric cancer, as well as upper urinary tract cancers depending on which MMR gene is mutated. 

Colorectal Colon Rectal CancerConnect 490

If one parent carries a gene mutation for Lynch syndrome, there's a 50% chance that mutation will be passed on to each child.

The understanding of Lynch syndrome has improved significantly over the past decade and continues to evolve. New mutations have been defined and cancer risk and screening continues to be optimized. Individuals with Lynch syndrome should be evaluated and managed by a genetic counselor that specializes in Lynch syndrome to ensure they understand the best current risk management strategies.1

Risk and Management

Because individuals with Lynch syndrome are at increased risk of developing cancer at an early age vigilance is required in order to prevent and detect cancer early when the cancer is most easily treated. Lynch syndrome is associated with an increased risk of several cancers, therefore it’s important to develop a cancer screening plan in collaboration with a genetic counselor who will develop screening guidelines for an individual’s specific genetic mutations and recommend lifestyle changes to prevent cancer. 

Screening tests are tests that are designed to detect cancer prior to the presence of any symptoms when cancer is in its earliest stages and most treatable. Depending on your unique situation, one or more of the following screening procedures may be recommended.1-6

  • Colorectal Cancer Individuals with Lynch syndrome are recommended to begin screening for colorectal cancer between the ages of 20-25 or 2 to 5 years prior to the age of onset of the earliest cancer in the family if it is diagnosed before age 25. Colonoscopy screening should be performed every one-two years. During a colonoscopy, polyps (precancerous growths) can be identified and removed to these reduce the risk of colon cancer. It is also recommended that individuals take an aspirin a day to reduce the risk of developing colon and other cancers. 
  •  Uterine Cancer Women with a Lynch syndrome gene mutation are 31 times more likely to develop endometrial (uterine) cancer. Currently the only test utilized to screen for uterine cancer is an endometrial biopsy. During an endometrial biopsy, a physician removes a small piece of tissue from the uterus to examine it for changes that may indicate cancer. Some women with Lynch syndrome, particularly those with a family history of uterine cancer, choose to undergo an annual endometrial biopsy during their annual pelvic exam. Screening or not, abnormal uterine bleeding is always cause for further evaluation. Because there is no clear evidence to support routine screening for uterine cancer annual endometrial biopsy remains optional. Anti-estrogen oral contraceptives and ovulation suppressing drugs can reduce the risk of developing endometrial cancer.
  • Ovarian Cancer Women with a Lynch syndrome gene mutation are 19 times more likely to develop ovarian cancer. Because ovarian cancers begin deep in the pelvis, they often do not cause any symptoms until they are at an advanced stage. Because women with Lynch syndrome have an increased risk of developing ovarian cancer, some clinicians believe that screening is warranted and current guidelines state that screening may be considered at the clinician’s discretion. There are two types of screening tests that can be used for ovarian cancer and neither has been shown to be sufficiently sensitive or specific:
    • Transvaginal ultrasound: A transvaginal ultrasound is an imaging procedure during which a physician inserts a probe into the vagina to examine the reproductive organs and bladder.
    • CA-125 blood biomarker
  • Urinary Tract Cancers Individuals with Lynch Syndrome are 11 times more likely to develop cancers associated with the urinary tract, currently there is no specific recommend screening test for these cancers. In early sign of a urinary tract cancer is blood in the urine and this can be detected with a simple urine analysis.  It is also possible to detect urothelial cancers by looking for microsatellite instability in the patient’s urine. Men with the MSH2 variant are at the greatest risk of developing cancer, with a higher than one in four risk of developing cancer of the kidney, ureter or bladder between the ages of 45 and 75.8 The NCCN suggests considering annual urinalysis beginning at age 25-30

Other Gastrointestinal Cancers

  • Pancreatic Cancer is also more common in families with Lynch syndrome and the risk is still being defined.  Current screening programs use either annual MRI screening or endoscopic ultrasound and are recommended to begin after age 50. To explore the frequency of pancreatic cancer in families with Lynch syndrome, researchers evaluated information from 6,342 individuals from 147 families with Lynch Syndrome.
    • 21% of the families reported at least one case of pancreatic cancer.
    • The risk of pancreatic cancer in families with Lynch Syndrome was 1.31% by the age of 50 and 3.68% by the age of 70. This risk is more than eight times higher than the risk in the general U.S. population.
  • Cancers of the Small Intestine The lifetime risk of small intestine cancer among individuals with Lynch Syndrome is roughly 4%. Routine use of invasive screening tests for small intestine cancer, such as double balloon enteroscopy is not currently recommended however individuals should discuss screening with their doctor.
  • Skin Cancer Lynch syndrome is associated with an increased risk of sebaceous skin cancer (which affects the sweat glands). It’s important to note any skin changes and report them to your doctor.
  • Breast Cancer Individuals with Lynch syndrome are 4 times more likely to develop breast cancer and annual screening mammography is recommended.
  • Prostate Cancer Men with Lynch syndrome are at increased risk of developing prostate cancer and it is currently recommended that Prostate Specific Antigen (PSA) screening begin at ~ age 40.
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Ask The Expert About Lynch Syndrome

Preventive Surgeries

Surgeries that are performed to remove at-risk organs prior to the development of cancer are called risk-reducing (or prophylactic) surgeries. Some people opt to undergo risk-reducing surgery in order to prevent cancer.2-3

Hysterectomy and Salpingo-oophorectomy

Because women with Lynch mutations are at increased risk of developing endometrial and ovarian cancers, there is interest in the extent to which cancer risk can be decreased by prophylactic preventive surgery. Some women mutation carriers elect to undergo surgical removal of their uterus (hysterectomy) and/or fallopian tubes and ovaries (salpingo-oophorectomy) before endometrial or ovarian cancer can devlop. Prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for preventing endometrial and ovarian cancer in women with Lynch syndrome. 

Given the median ages at which endometrial and ovarian cancers develop is 46 and 42 years respectively women should consider prophylactic surgery after the age of 30 - 35, or once childbearing has been completed. It’s also important to understand that gynecologic cancers associated with Lynch are predominantly at an early stage and curable at the time of detection, the costs of prophylactic surgery (including premature menopause and its sequelae) may outweigh the benefits. 


A colectomy is a surgery to remove the colon. This is a drastic measure that is generally only considered when someone is unable to undergo regular screening colonoscopy, as there is little evidence that a colectomy has any advantage over frequent cancer screening with colonoscopy.


Some research indicates that daily aspirin may be a viable preventive strategy for individuals with Lynch syndrome. Results of the CAPP2 clinical trial (Cancer/Adenoma Prevention Program) indicate that a minimum of two years of 600mg of daily aspirin can reduce the risk of colorectal and other cancers in Lynch syndrome by about 60 percent.6The protective effects of the aspirin were not evident until five years after the beginning of aspirin therapy.

Cancer risk varies bases on which of the 5 specific gene mutations an individual has inherited.

  • The EPCAM "Epithelial Cell Adhesion Molecule" gene is located on chromosome 2 and mutations in EPCAM cause Lynch syndrome by affecting the nearby MSH2 gene. The MSH2 gene protein plays an important role in repairing DNA damage. EPCAM increases the risk for many cancers but particularly cancers of the large intestine (the colon and the rectum) and uterus (endometrium). 
  • MLH1 stands for "MutL homolog 1." The gene is located on chromosome 3 and the MLH1 gene protein plays an important role in repairing DNA damage. Inherited mutations in the MLH1 gene are associated with Lynch syndrome.
  • MSH2 stands for "MutS homolog 2" gene which is located on chromosome 2 and the MSH2 gene protein plays an important role in repairing DNA damage.
  • MSH6 stands for "MutS homolog 6." The gene is located on chromosome 2 and the MSH6 gene protein plays an important role in repairing DNA damage. 
  • The PMS2 (PMS1 homolog 2, mismatch repair system component) gene is located on chromosome 7 and its protein plays an important role in repairing DNA damage. Children who inherit a PMS2 mutation from both their mother and father can have a rare syndrome known as “constitutional mismatch repair deficiency (CMMRD),” which can cause high risks of various cancers in childhood and young adulthood.


  1. Win AK, Young JP, Lindor NM et al. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. Journal of Clinical Oncology. Early online publication February 13, 2012.
  2. Kate GL, Kleibeuker JH, Nagengast FM et al. Is surveillance of the small bowel indicated for Lynch Syndrome families. Gut. 2007;56:1198-1201.
  3. Schmeler KM, Lynch HT, Chen L-M et al. Prophylactic Surgery to Reduce the Risk of Gynecologic Cancers in the Lynch Syndrome. New England Journal of Medicine. 2006;354:261-9.
  4. Offit K, Kauff ND. “Reducing the Risk of Gynecologic Cancer in the Lynch Syndrome.” New England Journal of Medicine. 2006;354:293-295.
  5. Dominguez-Valentin M, Sampson JR, Seppälä TT, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database [published online July 24, 2019]. Genet Med. doi: 10.1038/s41436-019-0596-9
  6. Burn J, Gerdes AM, Macrae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. The Lancet. 2011; 378: 2081-2087.
  7. Kastrinos F, Mukherjee B, Tayob N et al. Risk of pancreatic cancer in families with Lynch Syndrome. Journal of the American Medical Association. 2009;302:1790-1795.
  8. Molecular screening of urine for Mismatch Repair deficient urothelial tumours; an under-appreciated cancer in Lynch syndrome by Rachel Phelps et al. Short talks