Rectal cancer forms in the tissues of the rectum, the final several inches of the large intestine closest to the anus. This cancer, along with colon cancer, is grouped under the term colorectal cancer. Most rectal cancers begin as abnormal growths called polyps, typically taking many years to develop into cancerous tumors. Understanding the role of family history and genetics is important for personalized risk management and prevention.
Sporadic Versus Inherited Cases
The majority of rectal cancer cases are considered sporadic, meaning they arise from gene mutations acquired over a person’s lifetime, rather than being inherited at birth. These somatic mutations are often influenced by environmental factors, lifestyle choices, and aging.
A small portion of rectal cancers (approximately 5% to 10% of all colorectal cases) is directly linked to inherited genetic mutations passed down through families. These cases are attributed to hereditary cancer syndromes and result from germline mutations, which are alterations present in every cell of the body from conception. When cancer is hereditary, the individual is much more susceptible to developing the disease at a younger age.
Major Hereditary Cancer Syndromes
Two major genetic conditions account for most inherited rectal cancer risk, increasing the probability of developing the disease. These syndromes involve mutations in genes responsible for maintaining the integrity of the cell’s DNA.
Lynch Syndrome (HNPCC)
Lynch syndrome is the most common cause of hereditary colorectal cancer, accounting for about 2% to 4% of all cases. This condition is caused by inherited defects in one of four DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. The proteins produced by these genes are normally responsible for correcting errors that occur when DNA is copied during cell division.
When an MMR gene is mutated, the repair mechanism fails, leading to a rapid accumulation of errors throughout the cell’s genome, known as microsatellite instability. Individuals who inherit a Lynch syndrome mutation have a substantial lifetime risk of developing colorectal cancer (40% to 80%), often developing the disease before 50 years old. This syndrome also increases the risk for other cancers such as endometrial, ovarian, and stomach cancers.
Familial Adenomatous Polyposis (FAP)
Familial Adenomatous Polyposis (FAP) is a rarer, highly penetrant hereditary condition caused by a mutation in the APC gene. The APC gene is a tumor suppressor that prevents cells from growing and dividing too quickly. A mutation removes this cellular brake, leading to the characteristic development of hundreds to thousands of adenomatous polyps throughout the colon and rectum.
These polyps typically begin to appear during the teenage years, with cancer often developing by age 40. Without intervention, the lifetime risk of developing colorectal cancer for someone with classic FAP approaches 100%. A milder form, Attenuated FAP (AFAP), involves fewer polyps and a later age of cancer onset, but the risk remains elevated.
Family History and Genetic Counseling
Assessing personal risk begins with a detailed evaluation of your family health history for signs of a hereditary syndrome. Patterns that suggest an inherited risk include diagnosis of rectal or colon cancer before age 50 in multiple family members, or the presence of other Lynch syndrome-associated cancers like endometrial or ovarian cancer.
Genetic counseling involves a trained specialist reviewing this history to determine the likelihood of an underlying hereditary syndrome. The counselor explains the risks and benefits of genetic testing, which uses a blood or saliva sample to look for mutations in genes like APC or the mismatch repair genes. Knowing the precise genetic mutation allows for personalized risk management and provides information for relatives who may also be at risk.
High-Risk Screening and Surveillance
Individuals confirmed to have a hereditary syndrome require a different screening approach than the general population. Standard screening typically begins at age 45 or 50, but high-risk surveillance protocols start earlier and are more frequent.
For those with Lynch syndrome, a colonoscopy is recommended every one to two years, starting between ages 20 and 25. This schedule is necessary because the time it takes for a polyp to become cancerous is accelerated compared to sporadic cases. Women with Lynch syndrome also receive screening recommendations for endometrial and ovarian cancers.
For individuals with FAP, surveillance is intensified, often beginning with annual colonoscopy as early as age 10 to 12. Because the risk of cancer is nearly certain, most people with classic FAP undergo a prophylactic colectomy (surgical removal of the colon).