OVERVIEW

What is Lynch syndrome?

Lynch syndrome, also known as Lynch syndrome, is an autosomal dominant genetic disorder closely associated with cancer.

Patients have mutations in mismatch repair genes, which are present from birth. Currently, we understand that the essence of Lynch syndrome lies in genetic defects in five genes: MLH1, MSH2, MSH6, PMS2, and EPCAN.

What are the characteristics of Lynch syndrome?

Individuals with Lynch syndrome have an increased risk of developing colorectal cancer and endometrial cancer, as well as other malignancies such as ovarian cancer, gastric cancer, and skin cancer.

What should Lynch syndrome patients and their families pay attention to?

Lynch syndrome patients (and family members) should undergo regular screenings for specific cancers, such as colonoscopies for colorectal cancer, transvaginal ultrasounds for endometrial and ovarian cancer, and gastroscopies for gastric cancer.

Is Lynch syndrome common?

Lynch syndrome is the most common familial and hereditary cause of colorectal cancer, accounting for approximately 3% of newly diagnosed colorectal cancer cases and 2% of endometrial cancer cases.

How high is the risk of endometrial and ovarian cancer in women with Lynch syndrome?

Women with Lynch syndrome have a 27%–71% risk of developing endometrial cancer and a 3%–14% risk of developing ovarian cancer.

How high is the risk of colorectal cancer in Lynch syndrome?

The risk of colorectal cancer in Lynch syndrome can be as high as 70%.

SYMPTOMS

What are the common symptoms and manifestations of Lynch syndrome?

The common manifestations of Lynch syndrome include an increased risk of colorectal cancer, endometrial cancer, and several other malignancies:

• Colorectal cancer manifestations: Patients with Lynch syndrome develop colorectal cancer at a younger age (average age 44–61 years), typically with lesions occurring in the right colon, and the disease progresses more rapidly. Notably, most patients do not exhibit other symptoms before the onset of colorectal cancer symptoms, such as gastrointestinal bleeding, abdominal pain, or changes in bowel habits.

• Endometrial cancer manifestations: Patients with Lynch syndrome develop endometrial cancer at a younger age (average age 46–54 years), usually with lesions located in the lower uterine segment. Most Lynch syndrome-related endometrial cancers are diagnosed at an early stage, resulting in a favorable prognosis.

What are the complications of Lynch syndrome?

Patients with Lynch syndrome have a significantly increased risk of developing colorectal cancer, endometrial cancer, and other related cancers.

In addition, individuals with Lynch syndrome also face an elevated risk of ovarian cancer, gastric cancer, small intestinal cancer, hepatobiliary system cancer, transitional cell carcinoma of the renal pelvis and ureter, brain cancer (glioma), and sebaceous gland tumors.

CAUSES

What are the common causes of Lynch syndrome?

Lynch syndrome is a familial hereditary disorder primarily caused by mutations in DNA mismatch repair genes. These mutations are congenital and present in all normal cells of the body.

Currently, we know that Lynch syndrome is fundamentally linked to genetic defects in five genes: MLH1, MSH2, MSH6, PMS2, and EPCAN.

Which groups of people should be highly suspected of having Lynch syndrome?

To a large extent, current understanding of Lynch syndrome remains insufficient. According to the Amsterdam Criteria II, families meeting all the following criteria should be highly suspected of having Lynch syndrome:

• Three or more relatives with histologically confirmed Lynch syndrome-associated cancers (colorectal cancer, endometrial cancer, small bowel cancer, or transitional cell carcinoma of the renal pelvis or ureter), with one relative being a first-degree relative of the other two, and familial adenomatous polyposis excluded;
  
  
• Lynch syndrome-associated cancers affecting at least two generations;
  
  
• One or more cancers diagnosed before the age of 50.

How is Lynch syndrome assessed using the Amsterdam Criteria? What are its sensitivity and specificity?

The Amsterdam Criteria can be remembered using the 3-2-1 rule (3 affected family members, 2 generations affected, 1 person diagnosed before age 50).

The sensitivity and specificity of the Amsterdam Criteria II for diagnosing Lynch syndrome are 22% and 98%, respectively.

DIAGNOSIS

How is Lynch syndrome diagnosed?

For patients with synchronous or metachronous colorectal cancer, colorectal cancer occurring before the age of 50, or multiple Lynch syndrome-related cancers (such as colorectal cancer, endometrial cancer, ovarian cancer, gastric cancer, small bowel cancer, or renal pelvis/ureter cancer) showing familial clustering, Lynch syndrome can be confirmed if genetic testing identifies a DNA mismatch repair gene mutation.

Under what circumstances should genetic testing be performed for suspected Lynch syndrome?

We recommend genetic evaluation for Lynch syndrome in the following individuals:

• All newly diagnosed colorectal cancer (CRC) patients;
• Patients with endometrial cancer diagnosed before age 50;
• First-degree relatives of patients with known MMR/EPCAM gene mutations;
• Individuals with a predicted probability of MMR gene mutation greater than 5% based on prediction models;
• Individuals whose family cancer history meets the Amsterdam II criteria.

What tests are needed for colon cancer screening in Lynch syndrome? Why are these tests performed?

Colonoscopy is generally required for colorectal cancer screening, as it provides the most accurate results.

A colonoscope is a tube with a tiny camera that allows visualization of the entire colon during the examination. The end of the tube also has miniature tools, enabling the doctor to remove abnormal tissue if detected. The removed tissue is sent to a laboratory for cancer testing (called a biopsy).

What precautions should be taken for colonoscopy in Lynch syndrome?

Before a colonoscopy, the colon must be emptied by drinking a medication at home, such as polyethylene glycol electrolyte powder. This medication causes watery diarrhea for several hours to cleanse the intestines, ensuring clear visibility during the examination.

What are the risks of colonoscopy in Lynch syndrome?

Colonoscopy may cause internal bleeding or tears in the colon, but the incidence is only 1 in 1,000.

Which diseases can Lynch syndrome be easily confused with? How to differentiate them?

• Lynch syndrome can be confused with constitutional mismatch repair deficiency syndrome (CMMRD). CMMRD often causes hematologic and brain malignancies in childhood, whereas Lynch syndrome typically leads to malignancies such as colorectal and endometrial cancer between ages 40–59.
• Lynch syndrome can also be confused with familial colorectal cancer type X. Patients with familial colorectal cancer type X do not have an increased risk of endometrial cancer or other Lynch-related cancers.

TREATMENT

How is Lynch syndrome treated?

For individuals diagnosed with Lynch syndrome, both the patient and their family members should undergo regular screening for related cancers, such as colorectal cancer, endometrial cancer, ovarian cancer, and gastric cancer. The management of colorectal cancer is particularly critical and includes the following:

For Lynch syndrome patients diagnosed with colorectal cancer or adenomas that cannot be endoscopically resected, a total abdominal colectomy with ileorectal anastomosis is recommended, followed by annual endoscopic surveillance of the remaining rectum. Segmental colectomy with annual postoperative surveillance should only be considered for patients who are unsuitable for total colectomy.

What are the common risks of prophylactic hysterectomy and bilateral salpingo-oophorectomy for Lynch syndrome?

The most frequent surgical complications of these procedures include bleeding, infection, urinary tract or intestinal injury, menopause, and osteoporosis. The most significant consequences are infertility and menopause.

Under what circumstances should Lynch syndrome patients seek immediate medical attention for early detection of endometrial cancer?

To detect endometrial cancer early, women with Lynch syndrome should seek immediate medical attention if they experience abnormal uterine bleeding, such as irregular bleeding, heavy bleeding, or postmenopausal bleeding.

DIET & LIFESTYLE

What should patients with Lynch syndrome pay attention to in their diet and lifestyle?

Normal diet and lifestyle. No significant special requirements.

Does Lynch syndrome require follow-up examinations? How should follow-up be conducted after treatment for Lynch syndrome?

Follow-up examinations are necessary, and cancer screening should be performed as directed by the doctor.

PREVENTION

Can Lynch Syndrome Be Prevented?

Lynch syndrome is a genetic disorder and cannot be prevented.

Who Should Be Screened for Lynch Syndrome?

Young individuals (aged 20–25) with a family history of colorectal cancer and patients diagnosed with endometrial cancer should undergo screening for Lynch syndrome.

If Lynch syndrome is confirmed, their first-degree relatives can be tested to assess cancer risk and establish regular follow-up and intervention plans.

How Should Lynch Syndrome Patients Screen for Cancer?

• Colorectal cancer screening: Starting at age 20–25 or earlier (if there is a family history), undergo a colonoscopy every 1–2 years.
• Endometrial and ovarian cancer screening: Starting at age 30–35 or earlier (if there is a family history), have an annual gynecological exam and endometrial biopsy for endometrial cancer screening, along with transvaginal ultrasound for ovarian cancer. If childbearing is complete or around age 40, prophylactic hysterectomy and bilateral salpingo-oophorectomy are recommended.
• Gastric cancer: Starting at age 30–35, individuals with risk factors (e.g., gastric atrophy, family history of gastric cancer) should undergo gastroscopy every 2–3 years.
• Urinary tract cancers: Starting at age 30–35, have an annual urinalysis.
• Skin cancer: Lynch syndrome patients should undergo an annual skin examination.
• Other cancers: Starting at age 25–30, have an annual physical exam with special attention to neurological evaluation.

Can Aspirin Prevent Colorectal Cancer in Lynch Syndrome Patients?

Current research suggests that high-dose aspirin (600 mg/day) may benefit Lynch syndrome patients, but the optimal dosage remains uncertain. Long-term aspirin use for prevention should be decided by a doctor after weighing the risks and benefits based on individual clinical conditions.

Can Oral Contraceptives Prevent Endometrial or Ovarian Cancer in Lynch Syndrome Patients?

Studies indicate that oral contraceptives may reduce the risk of endometrial and ovarian cancer by 50%. However, regular monitoring for these cancers is still recommended even when using oral contraceptives for chemoprevention.