What Is Familial Adenomatous Polyposis?

Introduction

Familial Adenomatous Polyposis (FAP) or classic FAP is a rare genetic disorder characterized by the development of multiple polyps in the colon (large intestine) and rectum. These polyps are non-cancerous growths that can increase in number over time. If left untreated, they significantly raise the risk of developing colorectal cancer.

FAP is caused by mutations in the APC (adenomatous polyposis coli) gene, which is inherited from one or both parents. This hereditary nature makes 

FAP is a familial condition, meaning it can be passed down through generations in affected families. 

Individuals with FAP often start developing these polyps during their teenage years, and the number of polyps can increase rapidly. Classic familial adenomatous polyposis (FAP) is characterized by the existence of over 100 adenomas and an early onset of polyp formation.¹ A less severe variation of the condition, known as attenuated familial adenomatous polyposis (AFAP), also plays a role in the development of colorectal cancer. Individuals with AFAP tend to present at a later age and have a smaller number of polyps. Patients diagnosed with AFAP face a 70% risk of developing colorectal cancer while the risk of colorectal cancer in individuals with FAP is close to 100% by 40 years of age.² if not managed properly. 

How is FAP diagnosed?

Diagnosing FAP involves a combination of clinical evaluation, genetic testing to identify APC gene mutations, and imaging studies such as colonoscopy to detect the presence of polyps. 

Causes 

The cause is mainly linked to the role of APC gene mutations in FAP development and Inheritance patterns of FAP.

The development of Familial Adenomatous Polyposis (FAP) is closely linked to mutations in the APC (adenomatous polyposis coli) gene. This gene plays a crucial role in controlling cell growth and division, and when mutations occur in the APC gene, it leads to the formation of numerous polyps in the colon and rectum.  

Normally, the APC gene acts as a tumor suppressor, regulating the growth of cells and preventing the formation of polyps. However, in individuals with FAP, specific mutations disrupt the function of the APC gene, causing uncontrolled cell growth and the development of polyps. 

The inheritance pattern of FAP is autosomal dominant, meaning that a single copy of the mutated APC gene is sufficient to cause the condition. If one parent carries the APC gene mutation, there is a 50% chance of passing the mutated gene to their offspring. As a result, children of an affected parent have a 50% risk of inheriting FAP. However, the genetic mutation arises spontaneously in about 25 to 30 percent of individuals.

Due to the autosomal dominant inheritance pattern, FAP can occur in families, and multiple generations may be affected. Individuals with a family history of FAP need to undergo genetic testing and counselling to determine their risk of carrying the APC gene mutation. 

What factors increase the risk of colorectal cancer?

Numerous factors can elevate the likelihood of developing colorectal cancer. While some are beyond individual control, others can be influenced by lifestyle choices. 

•  Family History:

Individuals with a family history of the disease, particularly if a parent or sibling had it before age 55 or if multiple relatives were affected at any age, are at an increased risk.

• Genetics:

Around 20 percent of colon cancer cases arise from specific genetic mutations. This underscores the value of genetic testing.

• Age:

The incidence of colorectal cancer rises with advancing age. The recommended age for colorectal cancer screening has recently been adjusted from 50 to 45 years old due to the increasing occurrence in younger populations, particularly in specific ethnic groups. 

• Ethnic Origin:

FAP can affect individuals of any ethnicity, but certain genetic backgrounds may have a higher prevalence of the APC gene mutation.

Black and African Americans, individuals of Jewish Eastern descent, Native Americans, and Pacific Islanders face a higher risk.

• Presence of Polyps:

The presence of colon polyps heightens the risk, especially if they are sizable or numerous.

Personal medical history:

Having a prior diagnosis and treatment of colorectal cancer increases the likelihood of developing it again.

• Bowel Disorders:

Inflammatory bowel diseases like ulcerative colitis or Crohn’s colitis escalate the risk of colorectal cancer due to their prolonged inflammation of the colon.

• History of Ovarian, Uterine, or Breast Cancer:

Women who have experienced any of these cancers are at an elevated risk. 

Signs and symptoms of familial adenomatous polyposis (FAP):

Some common signs and symptoms of FAP include:

• Colorectal Polyps: The hallmark sign of FAP is the presence of numerous polyps in the colon and rectum. About 70 to 80%  of polyps are found on the left side of the colon. These polyps can be detected through screening tests like colonoscopy
• Abdominal Pain: Some individuals with FAP may experience abdominal pain, cramping, or discomfort, especially if the polyps are large or cause inflammation
• Changes in Bowel Habits: FAP may lead to changes in bowel movements, including diarrhea, constipation, or alternating between the two
• Rectal Bleeding: Bleeding from the rectum can occur if the polyps are large or bleed.
• Anemia: Chronic bleeding from polyps can lead to iron deficiency anemia, resulting in fatigue, weakness, and paleness
• Unintended Weight Loss: In advanced cases or if complications like cancer arise, unintentional weight loss may occur
• Eye Freckles: Certain individuals with FAP may exhibit minute freckles located at the rear of the eye (known as congenital hypertrophy of the retinal pigment epithelium CHRPE). These freckles don't impact vision or evolve into cancer

Complications 

The primary complication of FAP is colorectal cancer. Other complications are "extraintestinal manifestations," which means problems happening outside the intestines. These include:

• Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE), possibly appearing from birth, stands as the predominant and initial extraintestinal sign within FAP populations
• Bone lesions: Osteomas constitute a significant extraintestinal aspect of FAP, present in approximately 65% to 80% of individuals diagnosed with FAP
• Dental irregularities are identified in 30% to 75% of individuals diagnosed with FAP
• Others include Desmoid fibromatosis, Gardner-associated fibroma (GAF), and epidermal cysts⁴

Management and treatment of familial adenomatous polyposis (FAP):

The management and treatment of Familial Adenomatous Polyposis aim to reduce the risk of colorectal cancer and its associated complications. The approach may vary depending on the number and size of polyps, as well as individual factors such as age and overall health. Some key management and treatment options for FAP include: 

• Surveillance and regular screening: 

Individuals with FAP require regular surveillance to monitor the growth and development of polyps. Screening tests like colonoscopy are essential for early detection and timely intervention.

• Medications: 

Certain medications may be prescribed to help slow down polyp growth or reduce inflammation in the colon. Nonsteroidal anti-inflammatory drugs (NSAIDs) are sometimes used for this purpose and have   shown to reduce recurrence.⁵

• Surgical interventions: 

Surgical removal of polyps or affected areas of the colon may be necessary to manage FAP effectively. Surgical options may include polypectomy (removal of polyps), colectomy (partial or total removal of the colon), or proctocolectomy (removal of the colon and rectum).

• Prophylactic surgery:

In individuals at high risk of developing colorectal cancer, prophylactic surgery may be considered to remove the colon and rectum before cancer develops. As a preventive measure, prophylactic colectomy is commonly carried out before the age of 40 in individuals diagnosed with FAP. This procedure is widely regarded as the established treatment method to diminish the likelihood of colorectal cancer occurrence.^[5]

• Genetic counseling: 

Genetic counselling is an integral part of FAP management. It helps individuals and families understand their risk of developing FAP or passing the condition to their children. Genetic counselors provide valuable information to aid in making informed decisions about healthcare and family planning. 

• Supportive care: 

Managing FAP involves not only medical interventions but also supportive care. Emotional and psychological support can be crucial for individuals and families dealing with the challenges of living with a genetic disorder. 

FAP management team 

The management of FAP involves a multidisciplinary team which will include: 

• Gastroenterologist: Specializes in diagnosis and treatment of disorders of the gastrointestinal tract 
• Colorectal Surgeon: A colorectal surgeon is a specialist in surgical procedures related to the colon, rectum, and anus 
• Genetic Counselor: A genetic counselor is a professional trained to provide information and support regarding genetic conditions like FAP. They help individuals and families understand their risk of developing FAP, interpret genetic test results, and make informed decisions about family planning and healthcare
• Oncologist: An oncologist is a medical doctor who specializes in the diagnosis and treatment of cancer. They are involved in the management of FAP-related complications
• Pathologists:  They help in diagnosing FAP and identifying the characteristics of polyps and any potential cancerous change 
• Nutritionist/Dietitian: A nutritionist or dietitian provides guidance on dietary choices and nutrition to support overall health and manage symptoms related to FAP
• Psychologist/Counselor: A psychologist or counselor offers emotional and psychological support for individuals and families dealing with the challenges of living with a genetic disorder like FAP  

FAQs

1. Is colectomy linked to postoperative complications, and does it provide protection against extraintestinal manifestations of FAP?

Yes, colectomy is indeed associated with postoperative morbidity, meaning potential health issues following surgery. However, it's important to note that while colectomy effectively lowers the risk of colorectal cancer in FAP patients, it does not offer preventive measures against the development of extraintestinal manifestations associated with Familial Adenomatous Polyposis.⁵

2. Can lifestyle modifications influence FAP management?

While lifestyle changes cannot eliminate FAP, maintaining a healthy lifestyle, including a balanced diet and regular exercise, can contribute to overall well-being and potentially aid in managing the condition. 

3. What are some lifestyle factors that could raise the chances of getting colorectal cancer?

Lifestyle factors that might increase the risk of colorectal cancer include not getting enough exercise, eating a diet low in fruits and vegetables, having a diet that's high in fats and low in fiber, or consuming a lot of processed meats. Being overweight, drinking alcohol, and using tobacco are also factors that could contribute to this risk.⁶

Summary 

Familial Adenomatous Polyposis (FAP) is a rare genetic disorder characterized by the development of multiple polyps in the colon and rectum. It is caused by mutations in the APC gene and has an autosomal dominant inheritance pattern. Individuals with FAP may experience symptoms like abdominal pain, changes in bowel habits, and rectal bleeding. Early diagnosis involves clinical evaluation, genetic testing, and imaging studies.

The management of FAP aims to reduce the risk of colorectal cancer and its complications. Treatment options may include surveillance, medications to slow polyp growth and surgical interventions. Prophylactic surgery and regular screenings are vital for cancer prevention. FAP can also lead to extraintestinal manifestations like desmoid tumors and osteomas.

Genetic counseling is recommended for affected individuals and families to understand the inheritance pattern and make informed decisions about family planning and healthcare.