What Gastrointestinal Conditions can be Inherited?
The following is a small list of a few inheritable GI conditions:
- Colorectal Cancer Syndromes including:
- Familial Adenomatous Polyposis Syndrome (FAP) and
- Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer or HNPCC)
- Juvenile polyposis
- Hereditary Hemochromatosis
- Lactose Intolerance (this condition can be inherited, caused by injury or illness, or result due to prematurity in infants)
- Celiac disease
- Polycystic liver disease
- Autoimmune hepatitis
- Budd-Chiari syndrome
- Alpha-1-antitrypsin deficiency
- Wilson disease (a genetic disorder where excess copper builds up in the liver)
- Peutz-Jeghers syndrome
- Inflammatory Bowel Disease (Crohn’s disease and Ulcerative Colitis)
- Hirschsprung's disease
- Multiple Endocrine Neoplasia Type 1
How are Gastrointestinal Conditions Inherited?
Family history and genetics play a key role in the development of certain GI disorders. Not all GI disorders are inherited, and just because you have a family member with a certain GI condition doesn’t necessarily mean you’ll develop that same condition; however, family history is a crucial component to your medical history and it’s important that you share this information with us so that we can provide you with appropriate medical care in alignment with the recommended screening and surveillance guidelines specific to your condition.
Some GI disorders occur when you inherit a genetic mutation from one or both of your parents. Hereditary Hemochromatosis develops this way.
Hereditary Hemochromatosis causes your body to absorb too much iron from the foods that you eat or the supplements that you take. This excess iron is stored in tissues and organs like your liver and can cause severe organ damage. Most cases result from a mutation in the HFE gene, called C282Y. Other mutations include H63D. You need to inherit two copies of a mutated gene (meaning one copy from each of your parents) to develop the disease. People who inherit only one copy of the mutated gene (from one parent only) are known as carriers. In the case of Hereditary Hemochromatosis carriers typically don’t have symptoms. If they do, symptoms are usually mild. This is because the correct copy of the gene is still able to regulate the way your body absorbs iron, preventing iron overload and tissue/organ damage. You can still pass the condition on to your children, so knowing if you’re a carrier in the context of a strong family history and/or the appropriate clinical setting, can be valuable information for many patients.
Wilson's disease is a genetic disorder where excess copper builds up in the liver. It is caused by a mutation in the ATP7B gene, a protein responsible for transporting excess copper so that it can be excreted as waste. People with Wilson’s disease can’t remove copper properly and it builds up in the liver leading to copper toxicity and liver disease. The condition is autosomal recessive meaning you must inherit one mutated copy of the gene from both of your parents in order to develop the disease.
With Hereditary Hemochromatosis and Wilson’s disease if you inherit two copies of the mutated gene, it’s very likely that you’ll develop the disease. With other conditions, a certain gene is required, but just because you inherit that gene doesn’t necessarily mean you’ll develop the disease. A good example of this is Celiac Disease
Without the genes responsible for the development of celiac disease you will NOT develop celiac disease. These genes are located on the HLA-class II complex and are called DQ2 and DQ8. If you don’t have one of these genes (meaning your celiac genetic test is negative) you can’t possibly develop celiac disease. However, a positive genetic test doesn’t mean a diagnosis of celiac disease. Celiac disease is multifactorial, meaning it requires a positive genetic test, plus certain unknown environmental triggers in order for the disease to develop. The majority of people with a positive genetic test will never develop celiac disease. A positive genetic test increases the likelihood that you’ll develop the disease under the right environmental conditions compared with the general population, but it does NOT guarantee a diagnosis. Individuals with a positive genetic test but negative antibody testing or endoscopic biopies will need to be monitored closely for the development of celiac disease. This is because untreated celiac disease can lead to enteropathy associated T-cell lymphoma. Patients with untreated celiac disease have a substantially increased risk of developing this condition.
Finally, with many GI disorders one single gene can’t explain the condition. For example, about 15-20% of Crohn’s disease patients will have a first-degree relative (a parent or sibling) with the disorder. But Crohn's disease is also believed to be multifactorial; it develops due to a combination of genetic, lifestyle, and environmental factors. There’s not one specific genetic test available to guarantee a diagnosis in at risk individuals. A mutation in the NOD2 gene has been shown to be associated with an increased risk of developing the disease but this genetic test isn’t diagnostic. Carrying this mutation merely means you may be at increased risk for developing the disease compared with the general population.
For many GI conditions genetics is just one component to the development of the disease. This is why we emphasize diet and lifestyle modifications so much. A high fiber diet rich in whole grains, fresh fruits, and vegetables may lower your risk of developing certain GI conditions like IBS and diverticulosis. On the other hand, a diet high in red meats, animal fats, and processed foods may increase your risk of developing colon cancer, colon polyps, and diverticulosis. Poor sleep patterns, a sedentary lifestyle, smoking, excess stress, obesity, certain medications (like NSAIDs and aspirin), various viruses, and gut flora, unique to each of us, can all contribute to the development of GI diseases. Making small changes in your diet and lifestyle can go a long way in improving your overall health.
Inherited Colorectal Cancer Syndromes
Inherited colorectal cancer syndromes account for approximately 5-10% of colon cancers annually. The two most common inherited colorectal cancer syndromes are Lynch Syndrome (or Hereditary Nonpolyposis Colorectal Cancer, HNPCC) and Familial Adenomatous Polyposis (or FAP). Other less common inherited conditions exist and genetic tests are available to help evaluate for these conditions.
If you have a family history of colorectal cancer, especially in a first degree relative under the age of 50, in multiple family members, spanning generations, or in the context of other cancers, genetic counseling may be advised to help assess your individual cancer risk and better help you understand which types of genetic testing might be useful for you and your family. We strongly encourage you to discuss your family history in detail with us so that we can provide you with appropriate, evidence-based care that follows recommended screening and surveillance guidelines.
Familial Adenomatous Polyposis (FAP)
Familial Adenomatous Polyposis is a rare genetic condition that causes cancer of the large intestine and rectum. It accounts for roughly 1% of all colorectal cancers annually. Patients may have 100’s or even 1000’s of benign colorectal polyps. A milder form of the disease will sometimes present with fewer polyps. Polyps can occur early in life, sometimes as early as the teenage years, and 95% of affected individuals will develop polyps by the age of 35. The APC gene is responsible for this condition.
Lynch Syndrome or Hereditary Nonpolyposis Colorectal Cancer
Lynch Syndrome is the most common form of hereditary colon cancer. It accounts for about 3% of all colon cancers annually and is associated with an increased risk of kidney, ovarian, uterine, urinary tract, small intestine, liver, gallbladder, bile duct, brain, skin, and stomach cancers. Several gene mutations are thought to be responsible for the development of this condition. People with Lynch syndrome will often have a personal history of colorectal cancer under the age of 50, a family history of colorectal cancer at a young age, a family history of colorectal cancer spanning different generations, and a family history of other types of cancers including: endometrial, ovarian, kidney, stomach, small intestine, liver, and gallbladder or bile duct cancers.
How are Inherited GI Conditions Diagnosed?
Genetic testing is available for many of these conditions. Genetic testing helps us to diagnose certain conditions and identify asymptomatic family members. It helps us to establish the appropriate screening and surveillance guidelines for you based on current research guidelines. For example, if you have an inherited colorectal cancer syndrome, you’ll need to be screened for colorectal cancer beginning at a much younger age than what is recommended for the general population. Genetic testing may also be important in family planning for some individuals.
If you have a concern regarding a family history of certain GI conditions please contact our office for a comprehensive medical evaluation. Genetic counseling may be advised to help assess your own individual risk and to better help you understand which types of genetic testing might be useful for you and your family. We strongly encourage you to discuss your family history in detail with us so that we can best serve you, and to avoid missed diagnoses, delayed diagnoses, delayed care, and poor outcomes.