Familial adenomatous polyposis (FAP) and Lynch syndrome represent two of the most common inherited conditions that significantly increase an individual’s lifetime risk of developing colorectal cancer. While both predispose individuals to cancer, their underlying genetic causes, typical clinical presentations, and recommended management strategies differ considerably. Understanding these distinctions is therefore important for proper diagnosis and care.
Familial Adenomatous Polyposis (FAP)
Familial adenomatous polyposis is primarily caused by a mutation in the Adenomatous Polyposis Coli (APC) gene. This gene normally acts as a tumor suppressor, helping to control cell growth and division within the colon lining. A faulty APC gene leads to uncontrolled cell proliferation, resulting in the characteristic development of numerous polyps.
The defining feature of FAP is the appearance of hundreds to thousands of adenomatous polyps throughout the colon and rectum. These polyps typically begin to form during teenage years, though their onset can vary. Without intervention, nearly all individuals with FAP will develop colorectal cancer, often by the age of 40.
Beyond the colon, FAP can also lead to other growths. Individuals may develop desmoid tumors, which are non-cancerous but aggressive fibrous growths, often in the abdomen. Other associated features include osteomas (benign bone growths) and congenital hypertrophy of the retinal pigment epithelium (CHRPE), harmless pigmented spots on the retina. Diagnosis involves identifying numerous polyps during a colonoscopy and confirming an APC gene mutation through genetic testing.
Lynch Syndrome
Lynch syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), arises from inherited mutations in specific DNA mismatch repair (MMR) genes. The most commonly affected genes include MLH1, MSH2, MSH6, and PMS2, with mutations in EPCAM also sometimes implicated. These genes are responsible for correcting errors that occur during DNA replication, and when they are dysfunctional, DNA errors accumulate, increasing cancer risk.
Unlike FAP, individuals with Lynch syndrome do not typically develop a multitude of polyps. They may develop only a few colorectal polyps, if any, but these polyps have a higher likelihood of progressing to cancer at an earlier age. The lifetime risk of colorectal cancer for individuals with Lynch syndrome is significantly elevated, though it does not approach the near 100% risk seen in untreated FAP.
Lynch syndrome increases the risk for a broader spectrum of cancers beyond the colon. Endometrial cancer is particularly common, often surpassing colorectal cancer as the most frequent malignancy in affected women. Other associated cancers include ovarian, gastric, urinary tract, small bowel, and brain cancers. Diagnosis involves genetic testing for MMR gene mutations.
Key Distinctions and Overlap
A significant distinction between FAP and Lynch syndrome is the polyp burden in the colon. FAP is characterized by hundreds to thousands of adenomatous polyps, creating a dense carpet-like appearance. In contrast, Lynch syndrome typically presents with few or no polyps, though any polyps that do form carry a higher individual risk of malignant transformation.
The spectrum of associated cancers also differentiates these two conditions. FAP’s cancer risk is primarily concentrated in the colon and rectum, with almost all untreated individuals developing colorectal cancer. While FAP can have extracolonic manifestations like desmoid tumors or osteomas, these are distinct from the malignant extracolonic cancers seen in Lynch syndrome. Lynch syndrome, on the other hand, is notable for its elevated risk of multiple types of cancer, with endometrial cancer being a prominent concern, alongside ovarian, gastric, and other malignancies.
Despite their differences, both FAP and Lynch syndrome are inherited in an autosomal dominant pattern. This means that if a parent has either condition, each child has a 50% chance of inheriting the mutated gene. This shared inheritance pattern emphasizes the importance of family history and genetic counseling for affected families. Recognizing these distinct features allows for tailored screening and management strategies, as a one-size-fits-all approach would be insufficient given their unique profiles.
Management and Surveillance
Both FAP and Lynch syndrome necessitate proactive and lifelong surveillance due to their high cancer risks, though specific screening protocols are tailored to each condition’s unique presentation. A shared principle for both is genetic counseling, which helps individuals understand inheritance patterns and guides cascade testing for at-risk family members.
For individuals with FAP, management frequently involves prophylactic colectomy, the surgical removal of the colon, typically performed in late adolescence or early adulthood. This procedure prevents colorectal cancer due to the overwhelming number of polyps. Following colectomy, ongoing endoscopic surveillance of any remaining rectal tissue or the ileal pouch is necessary to detect new polyp formation. Upper endoscopy is also routinely performed to monitor for polyps in the stomach and duodenum, which can also occur in FAP.
Lynch syndrome management focuses on intensive and frequent surveillance rather than immediate prophylactic colon surgery. Regular colonoscopies, typically recommended every one to two years starting in early adulthood, are important to detect and remove any polyps before they become cancerous. For women with Lynch syndrome, gynecological screening is also important, including annual endometrial biopsies and transvaginal ultrasounds to detect endometrial and ovarian cancers early. Prophylactic hysterectomy and oophorectomy may be considered for women who have completed childbearing to significantly reduce their gynecologic cancer risks.