Diagnosis and management of Lynch syndrome


A personalised approach to lifelong gene-specific management for people with LS provides many opportunities for cancer prevention and treatment.

What surveillance should these patients undergo?

  • Colonoscopic surveillance should be performed every 2 years starting at age 25 years for MLH1, or MSH2 pathogenic variant carriers, or age 35 years for MSH6, or PMS2 pathogenic variant carriers.
  • Endoscopic lesions can be difficult to recognise due to a high frequency of flat non-polypoid morphology, and high-quality colonoscopy is essential.
  • Gynaecological surveillance has no proven benefit.
  • Aspirin reduces long-term colorectal cancer (CRC) risk by approximately 50%. Recommended doses include 150 mg ODonce daily or 300 mg ODonce daily for patients with BMIbody mass index >30.

What surgical treatments are recommended?

  • Women should be counselled on prophylactic hysterectomy and bilateral salpingo-oopherectomy from age 40 years (MLH1, MSH2 and MSH6 variant carriers).
  • There is a gene-specific approach to surgical management of CRC which takes in to account other patient factors.

What systemic oncological treatments are recommended?

  • Chemoprophylaxis with daily aspirin for at least 2 years is recommended in patients <70 years old diagnosed with LS to reduce long-term CRC risk.
  • Personalised systemic anticancer therapy is feasible for locally advanced or metastatic disease associated with LS, and may respond very well to relatively novel checkpoint inhibition immunotherapy.

Understanding Lynch Syndrome and Associated Cancer Risk: Epidemiology

Lynch syndrome is the most commonly inherited colon cancer syndrome, and it accounts for approximately 3% of all newly diagnosed cases of colorectal cancer.

The genetics of both the tumor and the germline have an important role in the development and diagnosis of Lynch syndrome. 

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment:

A report from the prospective Lynch syndrome database: The PLSD(www.PLSD.eu) is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up.


The current study found low CRC mortality in path_MMR carriers who receive colonoscopy surveillance while some extracolonic cancers were associated with high mortality. Further improvement of survival in LS may require a focus on the prevention and treatment of non-colorectal cancers, likely including approaches based upon the immune response to MSI pre-cancerous lesions and cancers.


Charity welcomes “game-changing” womb cancer treatment

Peaches Trust Press Release

Everyone diagnosed with advanced or recurrent endometrial cancer in England can access a new treatment that has been approved by The National Institute for Health and Care Excellence (NICE).

Approval of pembrolizumab (Keytruda), a type of cancer treatment called immunotherapy, and lenvatinib (Lenvima), a cancer growth blocker, will offer the potential for people with womb cancer to live longer, to feel well, and to live more independently, and with improved quality of life.


Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations


Despite the efficacy of premenopausal RRSO for reducing ovarian cancer risk and improving mortality in high-risk women, many women experience troublesome menopausal symptoms and oophorectomy may have adverse implications for long-term health.

Our panel of international experts has developed evidence-based recommendations for managing vasomotor, sleep, mood, sexual, and genitourinary symptoms and optimising bone and cardiovascular long-term health. Emerging evidence suggests that HRT reduces but does not eliminate the adverse effects of premenopausal oophorectomy. Women and clinicians considering RRSO should be aware of these risks and clinical care should focus on available safe options for symptom management and optimisation of long-term health.


Lynch Syndrome

Key Points

  •  Lynch syndrome is a rare, inherited condition that increases your risk of developing bowel cancer and sometimes other cancers. 
  • Lynch Syndrome accounts for about 3% of all bowel cancer.  
  • Regular bowel screening by colonoscopy can prevent bowel cancers developing.  
  • Bowel Screening usually starts from the age of 25 years and is performed on a yearly basis.  
  • People with Lynch Syndrome are also at increased risk of developing certain other cancers such as uterine (womb), urinary tract, ovary and small bowel.  
  • Women should consider screening of the uterus and ovaries from the age of 30-35 years.  
  • Genetic testing is available for families with this syndrome.  
  • When you have Lynch Syndrome, each of your children have a 1 in 2 (50%) chance of inheriting it.  


Acquired vs. Inherited Mutations in Cancer: What You Need to Know 

An example of an inherited risk of cancer is Lynch syndrome. A person with Lynch syndrome has an elevated risk of colorectal, endometrial, stomach, ovarian, urinary tract, other intestinal cancers, and additional cancers.

The increased risk is due to a mutation in one of several genes that fix mistakes made when DNA is copied. These genes are called DNA mismatch repair genes. The body has many mechanisms that work hard to prevent DNA copying errors and protect against cancer.

When one of those mechanisms is disabled by mutations, cancer is more likely to occur and at a younger age.

Is Colon Cancer Risk Hiding in Your Genes?

Most people diagnosed with colorectal cancer are at least 65 years old, but I was only 45 when doctors discovered my cancer, which they believed had been growing inside me for at least a decade. As someone who exercises regularly and maintains a healthy diet, I was shocked by my diagnosis. My doctors and I assumed that it was simply a case of bad luck.

“as many as 10% of colorectal cancer patients have an inherited gene mutation that caused their illness. I should know, because I was one of them.”

“I’ve heard people say that they don’t want to get genetic testing because there’s no way to prevent hereditary cancer, therefore it’s better not to know. But that couldn’t be further from the truth.”


Transforming Lynch Syndrome Limitations Into Opportunities

“I had to transform my challenges into opportunities.”

The key to focus on when we are confronted with challenges is to become focused on what is possible rather than what is not. 


Lynch Syndrome Cancer Risk to Age 70

Individuals with Lynch syndrome are at increased risk for multiple cancer types (common ones shown here). Note: MLH1 has the highest pancreatic cancer risk, MSH2 has the highest urothelial & prostate cancer risk, & PMS2 risks are mainly CRC & EC.

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