We do not yet know exactly what causes most esophageal cancers. However, there are certain risk factors that make getting esophageal cancer more likely. (See Esophageal Cancer Risk Factors.)
Scientists believe that some risk factors, such as the use of tobacco or alcohol, may cause esophageal cancer by damaging the DNA in cells that line the inside of the esophagus. Long-term irritation of the lining of the esophagus, as happens with reflux, Barrett’s esophagus, achalasia, Plummer-Vinson syndrome, or scarring from swallowing lye, may also lead to DNA damage.
Cancer is caused by changes in the DNA inside our cells. DNA is the chemical in each of our cells that makes up our genes – which control how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than how we look.
Some genes control when cells grow, divide into new cells, and die.
Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. This leads to cells growing out of control. Changes in many different genes are usually needed to cause esophageal cancer.
The DNA of esophageal cancer cells often shows changes in many different genes. However, it’s not clear if there are specific gene changes that can be found in all (or most) esophageal cancers.
For more about how genes changes can lead to cancer, see Genes and Cancer.
Some DNA mutations can be passed on in families and are found in all of a person's cells. These are called inherited mutations. A very small number of esophageal cancers are caused by inherited gene mutations. Some of these DNA changes and their effects on the growth of cells have been discovered and are being studied further. For example:
Special genetic tests can find some of the gene mutations linked to these inherited syndromes. If you have a family history of esophageal cancer or other symptoms linked to these syndromes, you may want to ask your doctor about genetic counseling and genetic testing. The American Cancer Society recommends discussing genetic testing with a qualified cancer genetics professional before any genetic testing is done. For more on this, see Understanding Genetic Testing for Cancer and What Happens during Genetic Testing for Cancer?
Most gene mutations that lead to cancer are acquired mutations. They happen during a person’s lifetime and are not passed on to their children.
In most cases of esophageal cancer, the DNA mutations that lead to cancer are acquired during a person’s life rather than having been inherited.
Certain risk factors, such as tobacco and alcohol use, probably play a role in causing these acquired mutations, but so far it’s not known what causes most of them.
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Ku GY and Ilson DH. Chapter 71 – Cancer of the Esophagus. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers. V.4.2019. Accessed at www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf on Jan 23, 2020.
Olson TS. Clinical manifestations and diagnosis of Fanconi anemia. Mahoney DH, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (Accessed on January 23, 2020.)
Posner MC, Goodman KA, and Ilson DH. Ch 52 - Cancer of the Esophagus. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019.
Spechler SJ. Barrett's esophagus: Epidemiology, clinical manifestations, and diagnosis. Talley NJ, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (Accessed on January 23, 2020).
Velleuer E, Dietrich R. Fanconi anemia: young patients at high risk for squamous cell carcinoma. Mol Cell Pediatr. 2014;1(1):9. doi:10.1186/s40348-014-0009-8.
Last Revised: March 20, 2020