What is Lynch syndrome?

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is an inherited genetic condition that increases the risk of developing certain types of cancer. People with Lynch syndrome have a higher risk of developing colorectal cancer, as well as other types of cancer, such as cancers of the endometrium, ovaries, pancreas, stomach, small intestine and urinary tract. Lynch syndrome is caused by mutations in certain genes that help repair errors in DNA. In particular, mutations in genes such as MLH1, MSH2, MSH6 and PMS2 can prevent cells from repairing errors that occur during DNA replication, leading to an increased risk of cancer.  Lynch syndrome is associated with an increased likelihood of developing colorectal cancer (10-47%), colorectal cancer (10-47%), colorectal cancer (10-47%) endometrial (27-71%), of ovarian (3-20%), stomach (11-19%), biliary tract (2-7%), urinary tract (4-5%) and, less frequently, skin, brain and small intestine.

How is Lynch syndrome inherited?

Lynch syndrome occurs in families with an autosomal dominant pattern of inheritance. This means that if a parent has genes that cause Lynch syndrome, there is a 50% chance that each child will have the genes that cause Lynch syndrome. Which parent carries the gene does not affect the risk.

How can Lynch syndrome be diagnosed?

Lynch syndrome can be diagnosed through genetic testing, which involves analysing a blood or saliva sample for mutations in the genes associated with the condition, such as MLH1, MSH2, MSH6, PMS2 and EPCAM. The test may be recommended for people who have a personal or family history of cancers associated with Lynch syndrome, such as colorectal, endometrial, ovarian or pancreatic cancer. In some cases, tumour screening can also be used to help diagnose Lynch syndrome. This involves analyzing a tumor tissue sample for specific molecular markers that are characteristic of cancers associated with Lynch syndrome. It is important to note that genetic testing for Lynch syndrome has implications not only for the individual being tested, but also for their family members. If a gene mutation is identified, close relatives may also be at increased risk and may benefit from genetic counseling and testing.

Who should be tested for Lynch syndrome?

There are several groups of people who are recommended to be tested for Lynch syndrome:

• People with a personal history of certain cancers: People who have been diagnosed with cancer of the colon, endometrium, ovaries, stomach, small bowel, pancreas or urinary tract at a young age (usually before the age of 50) may be recommended for Lynch syndrome.
• People with a family history of certain cancers: People who have a family history of these cancers, particularly in several generations or at an early age, may be recommended to be tested for Lynch syndrome.
• People with a personal or family history of multiple cancers: People who have been diagnosed with multiple cancers, particularly those associated with Lynch syndrome, or who have family members with multiple cancers may be recommended for Lynch syndrome testing.
• People with specific tumor characteristics: People who have been diagnosed with a tumour that has certain characteristics, such as high levels of microsatellite instability or abnormal expression of certain proteins, may be recommended to be tested for Lynch syndrome.

It is important to note that testing for Lynch syndrome is not recommended for everyone and should be based on a person's personal and family history of cancer.

What are the characteristics of endometrial cancer in patients with Lynch syndrome?

Endometrial cancer in patients with Lynch syndrome often has certain characteristics that differ from endometrial cancer in the general population. Here are some of the key features:

• Early age of onset: Endometrial cancer in patients with Lynch syndrome tends to occur at a younger age than in the general population, with an average age of onset of about 50 years.
• Increased risk: Women with Lynch syndrome have an increased risk of developing endometrial cancer during their lifetime, with estimates ranging from 25-60% depending on the specific gene mutation and other factors.
• Mainly endometrial cancer Type 1: The majority of endometrial cancers in patients with Lynch syndrome are Type 1, which is typically caused by estrogen and has a relatively good prognosis.
• High-grade tumors: Despite being type 1, endometrial cancers in patients with Lynch syndrome are often high-grade, which means that the cancer cells are more abnormal in appearance and tend to grow and spread more quickly.
• Tumours with specific genetic changes: Endometrial cancers in patients with Lynch syndrome often have specific genetic changes, such as mutations in the PTEN or PIK3CA genes, that are not often seen in sporadic endometrial cancers.

It is important to note that not all endometrial cancers in patients with Lynch syndrome have these characteristics and some may have features similar to sporadic endometrial cancers. However, understanding these potential differences can help physicians make informed decisions about screening, treatment, and genetic counseling for patients with Lynch syndrome.

What are the guidelines for screening and follow-up of Lynch syndrome-associated gynecological cancer?

Guidelines for screening for gynaecological cancer and follow-up for Lynch syndrome usually include screening that starts earlier and more frequently than for the general population. Here are some of the key recommendations:

Screening for endometrial cancer: Women with Lynch syndrome should have an annual endometrial biopsy starting at age 30-35 or 5 years before the first age of cancer diagnosis in the family, whichever is earlier. Alternatively, transvaginal ultrasound can be performed every 1-2 years starting at age 25-30 years, but biopsy is preferred.

Screening for ovarian cancer: There is currently no established method of screening for ovarian cancer in Lynch syndrome, but some experts recommend transvaginal ultrasound and CA-125 blood testing every 6-12 months starting at age 30-35 years. However, the effectiveness of this measure is not well documented.

Risk reduction surgery: Some women with Lynch syndrome and a strong family history of gynaecological cancer may choose to undergo risk-reduction surgery, such as removal of the uterus and/or ovaries, to prevent the development of cancer. This decision should be made in consultation with a gynaecological oncologist and genetic counsellor.

Monitoring for abnormal screening results: If an abnormality is detected on the endometrial biopsy or ultrasound, further evaluation and treatment, such as hysteroscopy, curettage or hysterectomy, may be needed.

What reproductive complications can Lynch syndrome have?

Lynch syndrome can be associated with various reproductive complications, such as:

Complications related to pregnancy: Lynch syndrome may be associated with an increased risk of pregnancy-related complications such as miscarriage, preterm birth and pre-eclampsia.

Transmission of Lynch syndrome: Lynch syndrome is an autosomal dominant genetic disorder, meaning that affected individuals have a 50% chance of passing the gene mutation to each of their children. This can have implications for family planning and genetic counseling.

What other tests should women with Lynch syndrome have?

In addition to gynaecological cancer screening, women with Lynch syndrome should also have regular screening for colorectal cancer and may need additional tests based on their individual risks. Here are some prevention suggestions:

→ Colon cancer screening: Regular colonoscopies are recommended for patients with Lynch syndrome starting from the age of 20-25 years or 2-5 years earlier than the youngest case of colorectal cancer in the family, whichever is earlier. Screening should be repeated every 1-2 years, depending on the presence and number of polyps.

→ Upper gastrointestinal cancer screening: Some studies suggest that Lynch syndrome may be associated with an increased risk of upper gastrointestinal cancers, such as stomach and pancreatic cancer. Screening for these cancers may be considered for people with a strong family history or other risk factors.

→ Urinary tract cancer screening: Lynch syndrome may also be associated with an increased risk of cancers of the urinary tract, such as cancer of the ureter and renal pelvis. Screening can be done for people with a strong family history or other risk factors.

→ Skin cancer screening: Some studies suggest that Lynch syndrome may be associated with an increased risk of certain types of skin cancer, such as sebaceous gland tumours. Regular skin screenings may be performed for people with a strong family history or other risk factors. It is important to note that these screening recommendations may vary depending on the specific gene mutation involved and other individual factors.