Nonpolyposis colorectal cancer

Below is a detailed description of the five named genes (EPCAM, MLH1, MSH2, MSH6, and PMS2) that are associated with the mismatch repair (MMR) system and are specifically implicated in the inherited cancer risk known as Lynch syndrome .

1. EPCAM (Epithelial Cell Adhesion Molecule)

• Role : EPCAM is a protein that promotes cell adhesion and aids in cell-cell communication. It is also involved in cell growth and differentiation. The EPCAM gene is not directly involved in mismatch repair, but certain mutations cause suppression of the MLH1 gene , which in turn affects the mismatch repair system.
• Associated Cancers : Mutations in EPCAM are associated with Lynch syndrome (hereditary nonpolyposis colon cancer: HNPCC) and specifically increase the risk of colon and endometrial cancer . These mutations cause epigenetic silencing of MLH1, inhibiting the MMR system.

2. MLH1 (MutL Homolog 1)

• Role : MLH1 is a central player in the DNA mismatch repair (MMR) system, which maintains DNA stability and prevents cancer development by correcting incorrect base pairs that occur during DNA replication. MLH1 works in conjunction with MMR proteins to ensure that DNA damage is accurately repaired.
• Associated Cancers : Associated with Lynch syndrome , there is a significantly increased risk of cancer, especially colon , endometrial , and other gastrointestinal cancers. MLH1 mutations impair DNA repair function, increasing the risk of cancer development.

3. MSH2 (MutS Homolog 2)

• Role : MSH2 is also involved in the DNA mismatch repair system and works with MLH1 to correct incorrect base pairs that occur during DNA replication. As part of the MMR protein, MSH2 plays an important role in the DNA repair process.
• Associated Cancers : Associated with Lynch syndrome , there is an increased risk of cancer, particularly colon and endometrial cancer . Mutations in MSH2 cause mismatch repair defects, which promotes the development of cancer by accumulating DNA damage.

4. MSH6

• Role : MSH6 is a gene involved in DNA mismatch repair along with MSH2. In particular, it plays a role in detecting and correcting errors during DNA replication. MSH6 works with other MMR proteins to maintain DNA stability.
• Associated Cancers : Associated with Lynch syndrome , there is an increased risk of colon cancer and endometrial cancer . Mutations in MSH6 increase the risk of cancer development by impeding DNA damage repair and causing the accumulation of genetic errors.

5. PMS2 (Postmeiotic Segregation Increased 2)

• Role : PMS2 cooperates with MLH1 and MSH2 in the mismatch repair system, which corrects errors during DNA replication. PMS2 plays an essential role in completing the MMR process.
• Associated Cancers : Associated with Lynch syndrome , there is an increased risk of cancer, especially colon and endometrial cancer . Mutations in PMS2 impair the function of the mismatch repair system, increasing the risk of cancer.

summary

These genes (EPCAM, MLH1, MSH2, MSH6, PMS2) are strongly associated with a hereditary cancer risk called Lynch syndrome , and particularly increase the risk of developing colon cancer and endometrial cancer . When these genes have mutations, DNA mismatch repair is not performed normally, leading to the accumulation of DNA damage and making cancer more likely to develop. Early prevention and cancer screening are possible by examining whether these genes have mutations through genetic testing.