A small number of esophageal cancers are linked to genes passed through families. But most esophageal cancers aren’t linked to a family history and don’t have a known cause.

Esophageal cancer makes up about 1% of cancers in the United States. The American Cancer Society estimates that about 21,560 people will receive a diagnosis of esophageal cancer in 2023.

In the United States, esophageal adenocarcinoma makes up about 80% of esophageal cancers. Most other cases are squamous cell carcinoma, which is the most common esophageal cancer worldwide.

Most people who develop esophageal cancer don’t have a family history of this condition. A small number of people inherit genes from their parents that increase their risk of developing esophageal cancer.

For example, inherited mutations in the RHBDF2 or BLM genes have been linked to squamous cell carcinoma. A family history of a condition called Barrett esophagus is linked to an increased risk of adenocarcinoma.

In this article, we take a deeper look at hereditary genes that increase the risk of esophageal cancer.

Language matters

In this article, we use “male” to refer to someone’s sex as determined by their chromosomes.

Sex is determined by chromosomes, and gender is a social construct that can vary between time periods and cultures. Both of these aspects are acknowledged to exist on a spectrum both historically and by modern scientific consensus.

Esophageal cancer occurs when gene mutations inside esophageal cells cause them to replicate uncontrollably. Genetic mutations can be inherited from your parents or acquired throughout your life. Researchers still aren’t sure if there are specific mutations found in most or all esophageal cancers.

Most people who develop esophageal cancer don’t have a family history, but researchers have identified some genes passed through families linked to an increased risk. These changes are seen in a very small number of people with esophageal cancer.

Esophageal adenocarcinoma that’s linked to a family history tends to develop at a younger age and is less strongly associated with other risk factors than cancer that’s not associated with a family history.

Tylosis with esophageal cancer

Tylosis with esophageal cancer, also called Howel-Evans syndrome, is caused by a genetic mutation in your RHBDF2 gene. It can develop if you inherit the mutation from one parent.

People with Howel-Evans syndrome have a higher risk of developing squamous cell carcinoma of the esophagus. The odds of developing squamous cell carcinoma by age 70 in people with the gene mutation are 40–90%.

Fewer than 1,000 people in the United States are thought to have Howel-Evans syndrome.

Bloom syndrome

Bloom syndrome is caused by mutations in the BLM gene. People with Bloom syndrome are at a higher risk of developing squamous cell esophageal cancer and some blood cancers such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia.

Most people with Bloom syndrome inherit the abnormal gene from both parents. Bloom syndrome is extremely rare, with only about 170 cases reported in the United States. It’s most common in people of Ashkenazi Jewish ancestry.

Up to 50% of people with Bloom syndrome develop cancer in their lifetime, and most of these cases occur under the age of 30.

Fanconi anemia

Fanconi anemia is caused by mutations in some FANC genes that increase your risk of:

  • AML
  • squamous cell esophageal cancer
  • progressive bone marrow failure

It only develops if you inherit a mutated gene from both parents.

Fanconi anemia affects about 1 in 136,000 newborns. It’s been found in all races, but in the United States, it’s most often seen in people of Ashkenazi Jewish ancestry.

Approximately 75% of cases are associated with developmental issues for a fetus.

Familial Barrett esophagus

Familial Barrett esophagus is a cluster of cases of Barrett esophagus within a family. Barrett esophagus occurs when cells in your esophagus change over time. It often occurs in people with chronic gastroesophageal reflux disease (GERD) and can develop into esophageal adenocarcinoma.

The exact genes linked to familial Barretts esophagus aren’t clear. Genes under investigation include the MSX1, CTFR, and VSIG10L genes.

A family history of Barrett esophagus or esophageal adenocarcinoma is a strong risk factor for Barrett esophagus and adenocarcinoma. Familial clustering is seen in about 6.5% of people with Barrett esophagus.

Research suggests that about 9% of cases of esophageal adenocarcinoma are linked to a family history of Barrett esophagus.

In a 2019 study, researchers found that people with Barrett esophagus who had a first degree family member with esophageal adenocarcinoma had a 5.5 times higher risk of progression to esophageal adenocarcinoma. A first degree family member can be a:

  • parent
  • full sibling
  • child

High use of tobacco products and high alcohol consumption are two of the leading risk factors for esophageal cancer.

The risk of getting adenocarcinoma is at least twice as high in somebody who smokes a pack a day versus a nonsmoker, and the increased risk remains elevated even if you quit smoking. The risk is higher for squamous cell carcinoma, but the risk decreases if you quit smoking.

Other risk factors for esophageal cancer include:

Esophageal cancer often doesn’t cause symptoms in the early stages. According to the American Cancer Society, the most common symptom is trouble swallowing. Other symptoms include:

Esophageal cancer often isn’t diagnosed until the cancer is advanced. It’s important to see a doctor if you develop symptoms of esophageal cancer without a known cause.

Most esophageal cancers aren’t linked to a family history. A small number of people receive genes from their parents that can greatly increase their risk of developing esophageal cancer.

Doctors don’t know what causes esophageal cancer in most cases. Avoiding tobacco and alcohol as well as eating a diet high in fruits and vegetables may help you lower your chances of developing esophageal cancer.