Common Causes Of Lynch Syndrome

Common Causes of Lynch Syndrome

Lynch syndrome (LS) is an autosomal dominant disorder occurs due to a genetic/germline mutation. It is also called hereditary non-polyposis colon cancer (HNPCC). The genetic mutation can be inherited or acquired (sporadic).

Common Causes Of Lynch Syndrome

There are no common causes for lynch syndrome. Lynch Syndrome is only caused by a germline mutation in one of several DNA mismatch repair (MMR) genes or loss of expression of MSH2 due to deletion in the EPCAM gene. The mismatch repair genes that are associated with Lynch syndrome include:

  • MLH1 (MutL homolog 1), which is located on chromosome 3p22.2
  • MSH2 (MutS homolog 2), which is located on chromosome 2p21-16
  • MSH6 (MutS homolog 6), which is located on chromosome 2p16.3
  • PMS2/ (postmeiotic segregation 2), which are located on chromosome 7p22.1
  • EPCAM (Epithelial Cell Adhesion Molecule)

Of these, MSH2 occurs with 60% frequency, MLH1 with 30% frequency & MSH6 with 7-10% frequency. Others genes mutations occur with rare frequency.

The genes responsible of lynch syndrome are MMR genes which correct the mistakes that occur in DNA during cell division. When the above genes are altered or mutated the mistakes in the DNA remains without any correction. If these mismatches accumulate in cell growth control genes, these will cause uncontrolled cell growth & tumor formation. The mutation of the above mentioned genes can be inherited or acquired.

A mutation in any of the above genes can give a person an increased lifetime risk of developing colorectal cancers (50-70%) & other cancers like endometrial (60%), ovarian(12%), stomach & small bowel cancers etc.

How Lynch Syndrome Is Inherited?

Most of the people with Lynch syndromes have inherited the disease. Normally, every cell has two copies of each gene: one inherited from the mother & the other one inherited form the father. As mentioned above lynch syndrome is an autosomal dominant disease.

Autosomal dominant illnesses are disorders that are available when only one copy of the mutation is inherited on a non-sex chromosome. In these illnesses, the candidate has one normal copy & one mutant copy of the gene. The abnormal gene dominates, masking the functions of the correctly functioning gene.

How Lynch Syndrome Is Acquired?

Some families with Lynch syndrome does not have identifiable mutations in the MLH1, MSH2, MSH6, PMS2, & EPCAM genes. Researches are ongoing to find if there are other gene mutations which can cause lynch syndrome. There is also a probability that mutations in the MLH1, MSH2, MSH6, PMS2, & EPCAM are not inherited but acquired & that is why some people does not have lynch syndrome in the family.

Mutations can occur by:

  • Aging – a single mutation that occurs in a cell will multiply over time & become a cancer. This explains why most cancers occur at a later age in life
  • Exposure to chemicals
  • Exposure to radiation
  • Hormones
  • Environmental factors

The above mentioned factors may cause mutations in the DNA of the cells & it will take some time for the mutated cells to multiply & form a cancer. Continuous exposure to the above factors may accelerate the mutated cell multiplication. These are still in research level therefore we cannot say exactly whether these gene mutations pass down to off springs or not.

Summary

Lynch syndrome (LS) is an autosomal dominant disease which is caused by a genetic/germline mutation in one of several DNA mismatch repair (MMR) genes or loss of expression of MSH2 due to deletion in the EPCAM gene. Genes that are associated with lynch syndrome are MLH1, MSH2, MSH6, PMS2 & EPCAM genes. The mutations can be inherited or acquired. Lynch syndrome mutated gene is inherited from either mother or father & only one copy of the gene is needed for the person to have lynch syndrome & there is a 50% chance of passing that gene to an offspring. Gene mutations can be acquired with aging, exposure to chemical, exposure to radiation, hormones & due to environmental factors.

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