Rectal cancer is a significant health concern. While many cases develop without a clear inherited link, a smaller proportion are connected to genetic factors passed down through generations. Understanding the distinction between inherited and non-inherited forms of the disease helps assess individual risk and identify those who might benefit from specialized screening or preventative measures.
Understanding Hereditary vs. Sporadic Rectal Cancer
Rectal cancer can arise in two main ways: sporadically or through inherited genetic predispositions. Most rectal cancers, approximately 85-90% of cases, are sporadic. These cases typically develop due to a combination of aging, environmental exposures, and lifestyle choices, rather than a specific inherited genetic mutation.
In contrast, hereditary rectal cancers, making up about 5-10% of all cases, result from germline mutations. These are genetic changes present in every cell of the body, inherited from a parent at conception. Such mutations increase a person’s lifetime risk of developing cancer. It is important to distinguish true hereditary cancer from “familial” cancer, where multiple family members may have cancer but without an identifiable inherited genetic pattern. Familial cancers often reflect shared lifestyle or environmental factors, or a combination of common genetic variations.
Major Hereditary Syndromes Linked to Rectal Cancer
Several genetic conditions significantly raise the risk of developing rectal cancer. The most common are Lynch syndrome and Familial Adenomatous Polyposis (FAP).
Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is caused by inherited mutations in mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, or PMS2. Individuals with Lynch syndrome have an elevated lifetime risk of colorectal cancer, often developing it at a younger age, typically before 50. They also face increased risks for other cancers like endometrial, ovarian, and stomach cancers.
Familial Adenomatous Polyposis (FAP) is another well-defined hereditary syndrome, stemming from a mutation in the APC gene. This condition leads to the development of hundreds to thousands of adenomatous polyps throughout the colon and rectum, usually starting in adolescence. If these polyps are left untreated, individuals with FAP face a nearly 100% lifetime risk of developing colorectal cancer, often by age 40.
Beyond Lynch syndrome and FAP, other less common syndromes can also increase rectal cancer risk. MUTYH-associated polyposis (MAP) results from mutations in both copies of the MUTYH gene, leading to an increased risk of colorectal cancer and often fewer polyps than FAP. Peutz-Jeghers syndrome (PJS), caused by a mutation in the STK11 gene, is characterized by distinctive pigmented spots on the skin and hamartomatous polyps in the gastrointestinal tract, elevating the risk for various cancers, including colorectal cancer.
Genetic Testing and Counseling
Genetic testing for hereditary rectal cancer is recommended in specific situations to identify individuals at increased risk. This includes those diagnosed with colorectal cancer before age 50, individuals with multiple family members affected by colorectal or related cancers, or those with specific tumor characteristics that suggest a hereditary syndrome. Testing typically involves analyzing a small sample of bodily fluid, such as blood or saliva, for inherited genetic changes.
Genetic counseling plays an important role before and after genetic testing. A genetic counselor helps assess an individual’s risk by reviewing personal and family medical history. These professionals explain the benefits and limitations of genetic testing, interpret the results, and discuss the implications for the individual and their family members. They also provide information on potential risk management strategies and guide communication with relatives about shared genetic risks.
Managing Risk and Prevention
For individuals identified with a hereditary predisposition to rectal cancer, specific strategies are implemented to manage risk and promote prevention. Increased surveillance, particularly through colonoscopies, is a primary tool. For instance, individuals with Lynch syndrome are often recommended to undergo colonoscopies every 1-2 years, starting between ages 20 and 25, or 10 years earlier than the youngest age of colorectal cancer diagnosis in their family. Those with FAP typically begin annual sigmoidoscopies or colonoscopies between ages 10 and 12 to monitor for polyp development.
Prophylactic surgery, such as a colectomy (removal of the colon), may be considered for conditions like FAP due to the nearly inevitable progression to cancer if polyps are left untreated. This surgery is often performed in early adulthood to prevent cancer development. While genetic factors are the primary driver in hereditary cases, adopting healthy lifestyle choices, including a balanced diet, regular exercise, and avoiding smoking and excessive alcohol, can complement medical management.
Communicating genetic risk information to family members is also important. Knowing about an inherited predisposition allows relatives to consider genetic testing and pursue appropriate screening and preventive measures.