We do not know exactly what causes most adrenal cortical tumors. Over the past several years, experts have made great progress in understanding how certain changes in a person's DNA can cause cells in the adrenal gland to become cancerous. DNA is the chemical in our cells that makes up our genes, which controls nearly everything the cells do. We usually look like our parents because they are the source of our DNA. But DNA affects more than just the way we look. It also determines our risk for developing certain diseases, including some types of cancer.
Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. Some people with cancer have inherited DNA mutations from a parent, which increase their risk for developing the disease. But most DNA mutations that are seen in cancers happen during life rather than having been inherited. Some of these mutations may result from exposure to things like radiation or cancer-causing chemicals. But most of these mutations seem to happen for no apparent reason, without having an outside cause.
Some of the DNA mutations that cause adrenal tumors in people with genetic syndromes are discussed in Adrenal Cancer Risk Factors. Overall though, these rarely cause adrenal cortical cancer. However, because adrenal cancer is so rare, if you have adrenal cancer, it may be worthwhile to consider genetic testing to find out if you have one of these syndromes. If you do, you (and your family members) might have an increased risk of developing other cancers also.
The Li-Fraumeni syndrome is caused by inherited mutations that inactivate the TP53 tumor suppressor gene. This syndrome causes a small portion of adrenal cancer in adults (about 1 of every 20), but it's often the cause of adrenal cancer in children. In fact, about 8 of every 10 cases of adrenal cancer in children are caused by Li-Fraumeni syndrome. Many other adrenal cancers have also been found to have TP53 gene changes that were acquired after birth (not inherited).
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Analysis of rare endocrine cancer reveals novel genetic alterations [press release]. National Cancer Institute (NCI) Press Office; May 9, 2016. Accessed at: https://www.cancer.gov/news-events/press-releases/2016/TCGA-adrenocortical on December 13, 2017.
Lirov R, Tobias E, Lerario AM, Hammer GD. Adrenal tumors In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2015: Chapter 84.
Online Mendelian Inheritance in Man, OMIM (TM). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), 07/26/16. Available at www.ncbi.nlm.nih.gov/omim/.
Schneider DF, Mazeh H, Lubner SJ, Jaume JC, Chen H. Cancer of the endocrine system In: Neiderhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, PA. Elsevier: 2014: 1112-1142.
Last Revised: January 2, 2018