Lynch Syndrome

1 What is Lynch Syndrome?

Also known as Hereditary NonPolyposis Colonic Cancer is a genetically inherited disorder characterized by a mutation in a mismatch repair gene in which affected individuals have a higher than normal chance of developing colorectal cancer, endometrial cancer, and various other types of aggressive cancers, often at a young age.

The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. It is a type of cancer syndrome.

2 Symptoms

Lynch syndrome symptoms include the occurrence of cancers and some other diseases.

The definition of Lynch Syndrome according to revised Bethesda classification includes:

  • Developing colorectal cancer at or before age 40.
  • Developing all cancers associated with Lynch Syndrome simultaneously or separately.
  • Developing colorectal cancer with tumor features linked to Lynch syndrome at an age younger than 60.
  • Colorectal cancer in one or more first-degree relatives who also has or has had another Lynch syndrome-related cancer*, with one of these cancers developing before age 50.
  • Colorectal cancer in two or more first- or second-degree relatives with another Lynch syndrome-related cancer.

Lynch syndrome-associated cancers include colorectal cancer, endometrial cancer, small bowel, ureter, or renal pelvis cancer; some people would also consider including ovarian cancer.

3 Causes

Lynch syndrome is caused by a pre-inherited condition, and it is genetic.

Lynch syndrome is a genetically inherited condition inherited in an autosomal dominant condition. Several genes have been identified to be associated which include: MLH1, MSH2, MSH6, PMS2, and EPCAM.

These are associated with instability of satellite chromosomes and hence increased cancer risks. The most common mutations are in MLH1 and MSH2 genes.

Mutations in the EPCAM gene also lead to impaired DNA repair, although the gene is not itself involved in this process.

The EPCAM gene lies next to the MSH2 gene on chromosome 2; certainEPCAM gene mutations cause the MSH2 gene to be turned off (inactivated), interrupting DNA repair and leading to accumulated DNA mistakes.

4 Making a Diagnosis

Diagnosis of lynch syndrome is on the basis of Amsterdam’s criteria which identifies individual for genetic testing and includes:

  • Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two
  • Two successive affected generations
  • One or more colon cancers diagnosed under age 50 years
  • Familial adenomatous polyposis (FAP) has been excluded

Amsterdam Criteria II:

  • Three or more family members with HNPCC-related cancers, one of whom is a first-degree relative of the other two
  • Two successive affected generations
  • One or more of the HNPCC-related cancers diagnosed under age 50 years
  • Familial adenomatous polyposis (FAP) has been excluded

5 Treatment

Surgery remains the front-line treatment for HNPCC.

There is an ongoing controversy over the benefit of 5-fluorouracil-based adjuvant therapies for HNPCC-related colorectal tumors, particularly those in stages I and II.

6 Prevention

Frequent cancer screening, preventive surgery and aspirin are options for reducing the risk of cancer in people with Lynch syndrome.

The best way to prevent disease is screening in families at risk and the best diagnostic criteria for screening are defined on the basis of Amsterdam’s criteria.

7 Lifestyle and Coping

Lifestyle modifications are necessary in order to cope with lynch syndrome.

Despite the odds, immense hope exists, thanks to modern technology and the passionate and diligent efforts of dedicated researchers and medical professionals.

Though no cure has yet been discovered, through genetic testing, the risk for cancer in families can be identified.

By exercising preventative measures (early diagnosis, surveillance, and treatment), enhanced the quality of life and longevity can be achieved and individuals and families can be protected from cancer.

8 Risks and Complications

There are several risks and complications associated with lynch syndrome.

Having no gender, ethnic or cultural preferences, Lynch syndrome targets families, predisposing them to cancer at a younger than average age. Children of a Lynch syndrome parent possess a 50% risk of acquiring a mutation.

Those with Lynch syndrome carry up to an 85% risk of contracting colon cancer as well as a higher than average risk for endometrial cancer, stomach, pancreas, kidney/ureter tract, hepatobiliary tract, gastric tract, prostate, ovarian, gallbladder duct, brain, small intestine common breast and skin cancers.

In the United States alone up to 1 million people are projected to have Lynch syndrome but only 5% are currently diagnosed.

Lynch syndrome is not a rare condition but rather an extremely under-diagnosed one.

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