Colorectal cancer is one of the most common cancers in Singapore. While lifestyle factors such as diet, physical inactivity, and smoking play an important role, genetics also influence an individual’s risk. Genetic mutations which are changes in the DNA sequence, can disrupt the normal regulation of cell growth and repair, allowing abnormal cells to multiply uncontrollably and eventually form cancer.
Is Colorectal Cancer Written in Your DNA?
These mutations can be classified into two categories: inherited (germline) mutations and non-inherited (somatic) mutations.
Inherited mutations are passed down from parent to child and are present in all cells from birth, often leading to a higher lifetime risk of developing colorectal cancer.
In contrast, non-inherited mutations occur during a person’s lifetime and are typically acquired through a combination of aging, environmental exposures, and random errors in DNA replication.
Certain hereditary conditions such as Lynch Syndrome, MYH-Associated Polyposis, and Familial Adenomatous Polyposis show the different ways inherited gene changes can increase cancer risk. Each of these conditions is associated with specific gene mutations and understanding them provides important insight into how inherited mutations contribute to cancer development.
1. Hereditary Non-Polyposis Colorectal Cancer (HNPCC) – Lynch Syndrome
Hereditary Non-Polyposis Colorectal Cancer, also known as Lynch Syndrome, is a genetic disorder that significantly increases the risk of colorectal cancer and other cancers, including endometrial and ovarian cancers.
It is caused by mutations in genes responsible for repairing DNA, including MLH1, MSH2, MSH6, and PMS2. Every time a cell divides, its DNA is replicated and small mistakes can occur during this process. Under normal circumstances, these genes identify and fix those errors.
In individuals with Lynch Syndrome, this repair system does not function properly. As a result, DNA errors accumulate over time, which can eventually lead to uncontrolled cell growth and the development of cancer.
Unlike other hereditary colorectal cancer conditions, Lynch Syndrome does not typically cause the formation of numerous polyps in the colon. However, affected individuals have a significantly higher risk of developing colorectal cancer, often at a younger age.
2. MYH-Associated Polyposis (MAP)
MYH-Associated Polyposis (MAP) is another hereditary condition that increases the risk of developing colorectal cancer. It is caused by mutations in the MYH (also known as MUTYH) gene, which plays an important role in repairing a specific type of DNA damage caused by oxidative stress.
Under normal conditions, the MUTYH gene helps correct errors that occur when DNA is damaged by everyday cellular processes. When both copies of this gene are defective, the body’s ability to repair such damage is impaired, allowing mutations to accumulate and increasing the likelihood of cancer development.
MAP is inherited in a recessive pattern, meaning that an individual must inherit two altered copies of the gene—one from each parent—to develop the condition. Individuals with only one defective copy are typically unaffected but may act as carriers.
Patients with MAP often develop multiple adenomatous polyps in the colon and rectum. These polyps are benign (non-cancerous) growths but carry a significant risk of progressing to colorectal cancer if left untreated.
3. Familial Adenomatous Polyposis (FAP)
Familial Adenomatous Polyposis (FAP) is an inherited condition characterised by the development of hundreds to thousands of adenomatous polyps in the colon and rectum.
It is caused by mutations in the APC gene, which plays a critical role in regulating cell growth and maintaining normal tissue structure. When this gene is not functioning properly, cells in the lining of the intestine grow and divide uncontrollably, leading to the formation of numerous polyps. Although these polyps are initially non-cancerous, they have a very high likelihood of becoming cancerous if left untreated.
FAP is often identified earlier in life, typically during adolescence or early adulthood. This is due to the large number of polyps that develop over a relatively short period.
If you have a family history of colorectal cancer, it is important to undergo regular screening. Early detection through colonoscopy, Faecal Immunochemical Test (FIT) or genetic testing can help identify problems before they become serious, allowing timely interventions to reduce your risk.