Risk Factors for Adrenal Cancer: What Genetics, Age, and Family History Actually Mean

Most guides about cancer risk open with a list of habits to change. This one cannot do that. The real risk factors for adrenal cancer are mostly things you were born with, not things you did. The American Cancer Society sums it up in a single line on its own risk factor page: scientists have found few risk factors for adrenal cancer, but having certain gene changes may increase your risk. That is why this guide leads with genetics, spends real time there, and then tells you plainly which risk factors are established, which are uncertain, and what you can genuinely act on. As always, bring your own history to your own care team, because they know your situation.

What Raises Your Risk for Developing Adrenal Cancer?

Adrenocortical carcinoma, the cancer of the adrenal cortex that most people mean by adrenal cancer, is genuinely rare. StatPearls, a peer-reviewed clinical reference, reports an annual incidence of 0.5 to 2.0 cases per million people worldwide, with roughly 300 to 400 new cases diagnosed each year in the United States. Two things are commonly confused with it, and neither is covered by the risk factors below. The first is cancer that started somewhere else and spread to an adrenal gland, which Cancer Research UK notes is actually more common than cancer that starts in the gland, and which is treated as the original cancer rather than as adrenal cancer. The second is a benign adrenal tumor, usually an adenoma found by accident on a scan. Most adrenal masses fall into that second group. Inherited syndromes explain a meaningful slice of those cases. StatPearls puts familial cancer syndromes at approximately 10% to 15% of adrenocortical carcinoma cases, and the American Cancer Society says most adrenal cortex cancers are not inherited, but some, up to 15%, are caused by a genetic defect, adding that this is more common in adrenal cancers in children. That is a far larger hereditary share than in most adult cancers, and it is the reason genetic counseling is a real recommendation in this disease rather than a footnote.

Here are the specific inherited conditions linked to adrenocortical carcinoma.

• Li-Fraumeni syndrome and the TP53 gene: This is the strongest and most important link. Li-Fraumeni syndrome is usually caused by an inherited change in the TP53 gene, a gene whose normal job is to stop damaged cells from dividing. GeneReviews, the National Institutes of Health clinical genetics reference, names adrenocortical carcinoma as one of the five core Li-Fraumeni cancers, alongside breast cancer, central nervous system tumors, osteosarcoma, and soft tissue sarcoma, and reports that adrenocortical carcinoma develops in 6% to 13% of people with the syndrome, most often as a childhood cancer. It can also appear in adulthood, typically before age 40. Inherited TP53 changes are uncommon overall, with GeneReviews estimating a prevalence between 1 in 3,000 and 1 in 10,000.

• Beckwith-Wiedemann syndrome: An overgrowth condition present from birth, often involving a large tongue, above-average growth, and sometimes one side of the body growing more than the other. StatPearls reports an overall tumor risk of about 5% to 10% in children with the syndrome, greatest in the first seven years of life, and lists adrenocortical carcinoma among the malignancies that can occur along with Wilms tumor and hepatoblastoma. The American Cancer Society also names adrenal cortex cancer among the risks. The National Cancer Institute lists Beckwith-Wiedemann syndrome and the related condition hemihyperplasia as risk factors for childhood adrenocortical carcinoma.

• Lynch syndrome: An inherited condition best known for raising colorectal and stomach cancer risk. The American Cancer Society lists adrenocortical cancer among the other cancers Lynch syndrome increases, and cites the research paper that established the link. Lynch syndrome is most often caused by a change in MLH1 or MSH2, though MSH6, PMS2, and EPCAM can also cause it. Cancer Research UK also lists Lynch syndrome among the inherited gene changes that raise adrenal cortical cancer risk.

• Multiple endocrine neoplasia type 1, also called MEN1: People with MEN1 have a high risk of tumors in the pituitary, parathyroid, and pancreas. The American Cancer Society reports that about one third to one half of people with MEN1 also develop adrenal tumors, and is careful to note that in most cases those adrenal tumors are benign adenomas that make no hormones. Some do make hormones such as aldosterone or cortisol. Cancer Research UK includes MEN1 in its list of inherited causes of adrenal cortical cancer.

• Familial adenomatous polyposis, also called FAP: Caused by changes in the APC gene, FAP produces hundreds of polyps in the large intestine. The American Cancer Society notes that people with FAP may develop tumors elsewhere, including the adrenal glands, but that most adrenal tumors in FAP are benign adenomas. StatPearls describes FAP as increasing adrenocortical carcinoma risk through activation of a growth signaling pathway called Wnt and beta-catenin. Cancer Research UK lists it as well.

• Carney complex: A rare inherited condition involving skin pigment spots, heart tumors called myxomas, and hormone problems. StatPearls reports that a specific adrenal condition called primary pigmented nodular adrenocortical disease is the most common endocrine finding in Carney complex, and that 60% to 70% of people with Carney complex and that adrenal finding develop Cushing syndrome. Frank adrenocortical carcinoma in Carney complex has been reported, but StatPearls describes those as case reports, so the honest framing is that adrenal involvement is central to this syndrome while outright adrenal cancer is uncommon. The National Cancer Institute nonetheless lists Carney complex as a risk factor for adrenocortical carcinoma, and Cancer Research UK does too.

• Neurofibromatosis type 1, also called NF1: NF1 is a well-established risk factor for adrenal tumors, but for pheochromocytoma of the adrenal medulla rather than for adrenocortical carcinoma of the cortex. The National Cancer Institute lists NF1 among the inherited syndromes that increase pheochromocytoma and paraganglioma risk, and Cancer Research UK does the same. NF1 does not appear on the National Cancer Institute, American Cancer Society, or Cancer Research UK lists of inherited causes of adrenocortical carcinoma, so if you have NF1, the relevant adrenal concern is the one covered in the pheochromocytoma section below.

• A family history of adrenocortical carcinoma or of these syndromes: The American Cancer Society advises that people with a family history of MEN1, or of pituitary, parathyroid, pancreas, or adrenal cancers, should ask their doctor whether they might benefit from genetic counseling, and its prevention page recommends considering genetic testing if you have a family history of adrenal cancer or related cancers. A pattern of cancers in your family, especially cancers appearing young, is meaningful information even if no one has ever been formally tested.

A specific TP53 change called p.Arg337His, also written R337H, is a very common variant in southern and southeastern Brazil, meaning it has been passed down widely from a shared ancestor. GeneReviews reports that it carries a very high risk of childhood adrenocortical carcinoma, and that in one series of people carrying it, adrenocortical carcinoma accounted for 55% of childhood cancers and 23% of adult-onset cancers. Its prevalence in that region is between 0.21% and 0.3%, which is roughly 1 carrier in every 300 to 500 people. StatPearls describes the consequence at the population level: in southern Brazil, childhood adrenocortical carcinoma occurs at 10 to 15 cases per million children, which is 10 to 15 times higher than worldwide averages. GeneReviews notes that this has led to newborn screening for the variant in Brazil, and that any childhood cancer in a person of southern or southeastern Brazilian ancestry should prompt consideration of testing. If your family has that ancestry, this is worth raising directly with a genetics professional.

Age is the next real risk factor, and it does not follow the usual pattern of steadily rising with each decade. StatPearls describes a characteristic bimodal age distribution, meaning two separate peaks: a first peak in children younger than 5 years, and a second, larger peak in adults during the fourth to fifth decades of life. Pediatric cases make up approximately 5% to 10% of all adrenocortical carcinoma diagnoses, with most occurring before age 15. The National Cancer Institute notes that most childhood adrenocortical tumors occur during the first five years of life, though they can also occur during adolescence. If you are reading this as the parent of a young child, that second fact matters: childhood adrenocortical carcinoma behaves differently and is treated differently, and the National Cancer Institute keeps a separate summary for it and says plainly that treatment for children differs from treatment for adults.

Your gender matters too. Adrenocortical carcinoma is more common in women than in men, and the gap is not small. StatPearls reports a consistent female predominance in adult cases, with a female-to-male ratio of 2.5 to 1 up to 3 to 1, and notes that the imbalance becomes more pronounced in younger adults. Nobody knows why. It is not something a woman does or fails to do. It is simply a feature of the disease, and it is worth knowing because it is one more reason for clinicians to take hormone symptoms in women seriously rather than defaulting to polycystic ovary syndrome or menopause. Our guide on adrenal cancer symptoms covers that pattern in detail.

There is no strong, established modifiable risk factor for adrenocortical carcinoma. Tobacco has been studied, and the results are not conclusive. StatPearls says only that some studies suggest associations with cigarette smoking, though these relationships require further validation. The American Cancer Society says smoking has been suggested as a risk factor for adrenal cancer, which is deliberately cautious wording. The American Cancer Society also mentions excess body weight, a sedentary lifestyle, and exposure to cancer-causing substances, but note carefully what it actually says: those factors can affect a person's risk of many types of cancer. It does not claim they are established causes of adrenal cancer specifically, and neither should we. Diet and supplements have no established role in adrenal cancer risk at all. Anyone selling you an adrenal cancer prevention plan built on food or supplements is going beyond the evidence.

Radiation is the one environmental exposure that can be associated with adrenal cancer. StatPearls lists prior ionizing radiation exposure to the head and neck region, with latency periods of 15 to 30 years, and describes occupational exposure to radioactive materials or therapeutic radiation treatments as an established risk factor. If you had radiation therapy as a child or young adult should be in your medical history and is worth mentioning to your care team. Beyond that, the most truthful summary is this: hereditary syndromes explain roughly 10% to 15% of cases, and for the remaining majority, StatPearls says the cause of adrenocortical carcinoma development is unknown. Most adults diagnosed with this disease have no identifiable risk factor. Nothing you did caused it, and there was very likely nothing you could have done differently.

Genetic Risk in Pheochromocytoma and Paraganglioma, Which Is Even More Strongly Inherited

Pheochromocytoma is a different adrenal cancer and works differently, including in its genetics. It arises from the adrenal medulla, the inner core of the gland, rather than the cortex, and paraganglioma is the same kind of tumor forming outside the adrenal gland. The two together are called PPGL, and their inherited component is far larger than in adrenocortical carcinoma. Both Cancer Research UK and the National Organization for Rare Disorders report that about 35% of cases are linked to an inherited gene change. Cancer Research UK adds that pheochromocytomas diagnosed in children and young adults are more likely to be linked to an inherited gene change, and that the average age at diagnosis overall is between 44 and 47.

The gene list is long. The National Organization for Rare Disorders states that PPGL may be caused by changes in at least ten different genes. The National Cancer Institute describes the same territory by syndrome name rather than by gene name.

• RET - multiple endocrine neoplasia type 2

• VHL - von Hippel-Lindau syndrome

• NF1 - neurofibromatosis type 1

• The succinate dehydrogenase subunit genes SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX - hereditary paraganglioma and pheochromocytoma syndromes

Which gene is involved matters because it influences where tumors form, how likely they are to spread, and how closely relatives should be watched.

Because of all this, genetic evaluation is standard rather than optional after a PPGL diagnosis. The National Cancer Institute states that all patients who are diagnosed with pheochromocytoma or paraganglioma should have genetic counseling to find out their risk for having an inherited syndrome and other related cancers. Cancer Research UK puts the practical version simply: you are likely to have genetic testing if you are diagnosed with a pheochromocytoma, and if an inherited gene change is found, your family members may be tested for the same change.

Factors That May Lower Your Risk of Adrenal Cancer

Let us be direct, because you deserve a straight answer rather than filler. There is no proven way to lower your risk of developing adrenocortical carcinoma. The American Cancer Society says: because adrenal cancer is quite rare, we do not yet have a way to prevent it. No diet prevents it. No supplement prevents it. No exercise plan prevents it. The main established risk factors are inherited gene changes, age, and sex, and none of those can be changed. If you have already been diagnosed, or your child has, nothing on this page is a list of things you should have done.

So here is a more useful way to think about it. You cannot meaningfully reduce your risk of getting adrenal cancer, but you can meaningfully reduce your risk of a late diagnosis. That distinction matters because stage at diagnosis drives outcomes in this disease, and StatPearls reports that more than half of patients already have stage III or stage IV disease when they are diagnosed. Complete surgical removal of the tumor is the single most important prognostic factor, which means that being found earlier and getting to a surgeon who does these operations often is where a patient actually has leverage. Everything below is aimed at that goal rather than at prevention.

• Genetic counseling and testing when your history suggests a syndrome: This is the most valuable action on this list. The American Cancer Society's prevention page explicitly recommends considering genetic testing if you have a family history of adrenal cancer or related cancers, and its risk factor page recommends asking about genetic counseling if your family has MEN1 or pituitary, parathyroid, pancreas, or adrenal cancers. Cancer Research UK advises speaking with your primary care doctor if you have a family history of pheochromocytoma or one of the family cancer syndromes, so you can be referred to a family cancer clinic for assessment. Testing does not change your genes. It changes what your doctors watch for, in you and in your relatives.

• Enrolling in a surveillance program if a syndrome is confirmed: There is no population screening for adrenal cancer, and there should not be, because the disease is far too rare for that to make sense. What does exist is surveillance for people known to carry a high-risk gene change. Cancer Research UK notes that people at increased risk of pheochromocytoma might have screening tests to pick up tumors at an early stage, and GeneReviews notes that the high risk of childhood adrenocortical carcinoma in TP53 p.Arg337His carriers has led to newborn screening for that variant in Brazil. The specific tests and the specific intervals depend on which syndrome you have and are set by your genetics and endocrinology team, so ask them for a written surveillance plan rather than assembling one yourself. Our guide on adrenal cancer screening explains this in more detail.

• Getting hormone symptoms properly evaluated instead of accepting a vague explanation: Cortisol excess, aldosterone excess, and sex hormone excess all produce measurable changes in blood and urine. The NIDDK notes that Cushing syndrome may be mistaken for other conditions with many of the same signs, such as polycystic ovary syndrome or metabolic syndrome, so the point of testing is to settle the question rather than to guess. If several hormone symptoms have appeared together and kept progressing, it is reasonable to ask directly for cortisol and potassium testing and to ask why, if the answer is no.

• Having an adrenal mass found on a scan properly worked up: Most adrenal masses found by accident are benign adenomas, and Cancer Research UK notes that these often need no treatment. But "probably nothing" is the same as "checked." The correct response to an incidental adrenal mass is a defined workup: hormone testing to see whether it is making anything, and imaging characteristics and size to judge whether it looks worrying. Ask for the plan in writing, including when the follow-up scan is due and who is responsible for ordering it. Masses get lost between specialties more often than anyone would like.

• Not smoking: The evidence tying tobacco to adrenal cancer specifically is weak and inconsistent, and this guide is not going to pretend otherwise. But the American Cancer Society's adrenal cancer prevention page still lists avoiding smoking, along with avoiding exposure to cancer-causing chemicals, under general recommendations to lower cancer risk. Quitting is worth doing for many well-established reasons, and it also improves how well you tolerate surgery and other treatment if you ever need it.

• General health measures: Staying physically active, eating reasonably, keeping blood pressure and blood sugar under control, and keeping up with the rest of your health care will not lower your chance of getting adrenocortical carcinoma. What they do is improve your baseline fitness for major abdominal surgery, your tolerance of chemotherapy, your recovery, and your day-to-day well-being. In a disease where the best outcomes follow a complete operation done by an experienced surgeon, being in the best shape you can be is not a small thing.

Finally, if you carry a hereditary syndrome, the actions above extend to your family. A confirmed gene change in one person tells siblings, parents, and children something they can act on, and the National Cancer Institute notes that when a gene change is found through testing, testing is usually offered to at-risk family members who have no signs or symptoms. That conversation is hard to start and worth starting anyway. A genetic counselor can help you decide what to share and how. Our guides on adrenal cancer prevention and adrenal cancer facts cover related ground, and adrenal cancer support can connect you with others navigating the same questions. Every decision about testing, surveillance, and treatment belongs to you and your own care team.

Sources:

• What Is Adrenocortical Carcinoma?, National Cancer Institute

• Childhood Adrenocortical Carcinoma, National Cancer Institute

• Adrenal Cancer Risk Factors, American Cancer Society

• Adrenal Cortical Cancer, Cancer Research UK

• Pheochromocytoma and Paraganglioma, National Organization for Rare Disorders