Causes and Risk Factors – Cystic Fibrosis


Cystic fibrosis is an inheritable and life-threatening disorder that affects roughly 30,000 Americans and as many as 70,000 people worldwide.

It is caused by a genetic defect in the cystic fibrosis transmembrane receptor (CFTR) gene, which creates the protein involved in the production of sweat, digestive fluids, and mucus. If there is a defect in this protein, it can lead to the abnormal accumulation of mucus in lungs, the blockage of digestive enzymes to the intestines, and other serious symptoms and complications.

There are at least 1,700 or more known CFTR mutations. In order for you to have cystic fibrosis, you need to have inherited two copies of the CFTR mutation, one from each parent. While advances in diagnosis and treatment have increased the life expectancy of people living with the disease, there is still no cure.



Cystic fibrosis (CF) is an autosomal recessive disorder. This is the type of disease you can only inherit if both of your parents contribute a single copy of a recessive gene (in this case, the CFTR mutation).

By definition, a recessive gene is one that can be masked by a dominant gene. One such example is blue eyes, which is a recessive trait, and brown eyes, which is a dominant trait. If you only inherit one recessive gene, you wouldn’t exhibit the recessive trait but would instead be a carrier of the gene.

With regards to CF, you can inherit the disease if each of your parents is a carrier of the CFTR mutation. Unfortunately, there is nothing a parent can do to influence the odds of inheritance one way or the other.

Risk of Inheriting Cystic Fibrosis

If both parents are carriers of the CFTR gene mutation, you would have a:

  • 25% chance of inheriting two copies and having CF
  • 50% chance of inheriting one copy and being a carrier
  • 25% chance of inheriting no mutations and being unaffected

Race and Ethnicity

More than 10 million Americans have a CFTR mutation and as many as 2,500 babies are born with cystic fibrosis each year.

The actual rate of babies born with CF is around:

  • 1 in 2,500 Caucasian-Americans
  • 1 in 15,000 African-Americans
  • 1 in 35,000 Asian-Americans
  • 1 in 13,500 Hispanic-Americans

The country with the highest rate of babies born with CF is Ireland, in which one of every 1,353 newborns are affected, according to a 2017 epidemiological study published in the Biomedical and Biotechnology Research Journal.

Types of CFTR Mutations

Not all CFTR mutations are created equal. Depending on the source, mutations are divided into six classes based on the characteristics of the defect and their impact on the body. Classes 1, 2, and 3 will result in the most severe “classic” symptoms of CF, while classes 4, 5, and 6 are milder by comparison.

The role of the CFTR protein is to control the movement of water and salt in and out of cells. By doing so, it helps regulate the production of mucus, sweat, saliva, tears, and digestive enzymes. Based on how defective the protein is, these systems can malfunction in often serious ways.

The classes of CFTR mutations can be broadly described as follows:

  • Class 1: The mutation results in the production of few or no CFTR.
  • Class 2: The mutation causes CFTR to be deformed and non-functional.
  • Class 3: The mutation causes a “gating defect” to where CFTR blocks the movement of water and salt in and out of cells.
  • Class 4: The mutation causes a “conductance defect” to where CFTR restricts the movement of salt in and out of cells.
  • Class 5: The mutation decreases the production of CFTR protein.
  • Class 6: The mutation results in functional and unstable CFTR that need to be constantly replaced.

Different mutation combinations can lead to different classes of disease. One such example is the ΔF508 mutation seen in around 70% of cases. Other genes, called modifying genes, can further degrade protein function and lead to a worsening of symptoms.


You can best understand how CFTR defects cause cystic fibrosis, you need to look closer at systems that the protein is meant to regulate.

The CFTR protein is referred to as a channel protein. It is produced by the body with the single aim of maintaining the balance of water and salt in cells. Under normal circumstances, if there is anything that affects this balance, CFTR will move water and salt in and out of the cell to maintain stasis (equilibrium).

With cystic fibrosis, the CFTR protein functions abnormally. Rather than moving water in and out of cells, the water becomes trapped, causing mucus outside of the cell to thicken and accumulate.

This accumulation will interfere with the normal function of organs in different ways:

  • In the lungs, the accumulation of mucus can block airways, causing inflammation and an increasing the risk of infection, pulmonary hypertension, and tissue damage.
  • In the digestive tract, the accumulation can block the secretion of digestive enzymes from the pancreas. This can interfere with the absorption of nutrients in the intestines, leading to malnutrition and poor growth. Chronic pancreatitis can also occur.
  • In the liver, the blockage of bile ducts can interfere with the liver’s ability to clear toxins from the blood, leading to scarring, gallstones, and cirrhosis.
  • In the reproductive system, abnormalities in the CFTR protein causes structural problems that renders the majority of men with CF infertile. Women’s anatomy is not affected, but they may have thicker than normal cervical mucus as well as irregular menstrual cycles, both of which can interfere with conception.
  • In the endocrine system, the blockage of insulin-producing cells on the pancreas, known as islets of Langerhans, can lead to a type of diabetes that has characteristics of both type 1 and type 2 diabetes. This is called cystic fibrosis-related diabetes (CFRD).

Cystic Fibrosis Doctor Discussion Guide

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Disease Progression

The only risk factor for getting CF is having two parents who carry abnormal CFTR genes. That said, there are factors that can influence the severity and progression of the disease.

Chief among these is the timing of diagnosis and treatment. Newborn screening is considered vital as it allows immediate treatment of the disease. Doing so can slow or prevent the damage that can occur in early childhood.

Research has found children who are treated after CF symptoms appear will usually have significant airflow impairment and signs of respiratory injury by age 2. By comparison, children identified and treated at birth will, by the age of two, have lung function comparable to a 1-year-old in the delayed treatment group.

Early treatment, along with advances in drug therapies, means that children diagnosed with CF today may live well into their 40s and 50s and remain largely unencumbered by the disease.

Despite advances in diagnosis and treatment, challenges remain. In the end, cystic fibrosis is influenced as much by things we can control as things we can’t.

Among the risk factors linked to poorer outcomes:

  • Poor growth is the factor most strongly associated with severe CF lung disease, according to research from the University of Wisconsin. To this end, people with CF need to consume a very large number of calories to maintain weight and growth, which is often difficult if there is serious intestinal involvement.
  • Antibiotic under-treatment is another common risk factor. Due to the high risk of bacterial infections, people with CF are commonly placed on prophylactic (preventive) antibiotics even if they are healthy. Under-treatment can increase the risk of infection, while the inconsistent use of antibiotics over the long term can lead to resistance, limiting treatment options in the future.
  • Pseudomonas aeruginosa infection, a bacterium commonly acquired by people who have been in the hospital for more than a week, is associated with rapid disease progression. As such, hospitalization is considered an independent risk factor for CF progression.
  • Alcohol use can accelerate liver damage while increasing the risk of acute or chronic pancreatitis, according to a 2015 study published in the journal Gastroenterology.
  • Secondhand smoke increases your risk of infections and complications almost as much as smoking itself. According to research from the John Hopkins University School of Medicine, secondhand smoke is associated with a 10% decrease in lung capacity and function. While this may not seem like a severe loss, it ultimately means that a 17-year-old with CF exposed to secondhand smoke would have the same lung function as a 24-year-old with CF who has not been exposed.

Frequently Asked Questions

  • How is cystic fibrosis inherited?

    You have two copies of the CFTR gene with one coming from each parent. If both parents pass on a mutation of the CFTR gene, you may inherit cystic fibrosis. Parents can pass on the mutation if they have the disease themselves or if they’re just carriers of the mutation (with no symptoms). 

  • Can cystic fibrosis be prevented?

    If a person inherits two copies of the CFTR mutation, then it’s not possible to prevent cystic fibrosis (CF). However, with genetic screening, potential parents can determine their risk for passing on CF and make a decision about whether or not to have a child. Also, a person born with CF can take steps to manage the condition and prevent serious complications such as cor pulmonale.

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