CAUSES, RISK AND PREVENTION OF ADRENAL CANCER

what causes adrenal cancer?

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 molecule that carries the instructions for nearly everything our cells do. We usually look like our parents because they are the source of our DNA. However, DNA affects more than the way we look. It also determines our risk for developing certain diseases, including some types of cancer.

Some genes (parts of our DNA) control when our cells grow and divide. Some genes that promote cell division are called oncogenes. Other genes that slow down cancer cell division or make them die are called tumor suppressor genes. We know that cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. Some people with cancer have DNA mutations they inherited 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. These mutations may result from exposure to radiation or carcinogens (cancer-causing chemicals). But most of these mutations happen for no apparent reason.

The DNA mutations that cause tumors in people with the genetic syndromes discussed in the previous section have been identified. 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) may have an increased risk to develop other cancers also.

The Li-Fraumeni syndrome is caused by inherited mutations that inactivate the p53 tumor suppressor gene. This syndrome causes few cases of adrenal cancer in adults (1 of every 20), but is 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 abnormal p53 genes that were acquired after birth (not inherited).

risk factors for adrenal cancer?

A risk factor is anything that changes your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

Scientists have found few risk factors that make a person more likely to develop adrenal gland tumors. Even if a patient does have one or more risk factors for adrenal gland tumors, it is impossible to know for sure how much that risk factor contributed to causing the cancer.

But having a risk factor, or even several, does not mean that you will get the disease. Many people with risk factors never develop adrenal cancer, while others with this disease may have few or no known risk factors.

Genetic syndromes

The vast majority of adrenal cortex cancers are sporadic (not inherited), but some (up to 15%) are caused by a genetic defect. This is more common in adrenal cancers in children.

Li-Fraumeni syndrome

The Li-Fraumeni syndrome is a rare condition which is most often caused by a defect in the TP53 gene. People with this syndrome have a high risk of several types of cancers, including include breast cancer, bone cancer, brain cancer, and adrenal cortex cancer.

Beckwith-Wiedemann syndrome

People with this problem have large tongues, are large themselves, and have an increased risk for developing cancers of the kidney, liver, and adrenal cortex.

Multiple endocrine neoplasia (MEN1)

People with MEN1 have a very high risk of developing tumors of 3 glands: the pituitary, parathyroid, and pancreas. About one-third to one-half of people with this condition also develop adrenal adenomas or enlarged adrenal glands. These usually do not cause any symptoms. This syndrome is caused by defects in a gene called MEN1. People who have a family history of MEN1 or pituitary, parathyroid, pancreas, or adrenal cancers should ask their doctor if they might benefit from genetic counseling.

Familial adenomatous polyposis (FAP)

People with this syndrome develop hundreds of polyps in the large intestine. These polyps will lead to colon cancer if the colon is not removed. FAP also increases the risk of other cancers, and may increase the risk for adrenal cancer. Still, most adrenal tumors in patients with FAP are benign adenomas. This syndrome is caused by defects in a gene called APC.

Hereditary nonpolyposis colorectal cancer

Patients with hereditary nonpolyposis colorectal cancer (HNPCC, also called Lynch syndrome) have a high risk of colorectal cancer as well as, in women, endometrial cancer. They also have an increased risk of some other cancers, including cancer of the adrenal cortex.

In most cases, this disorder is caused by an inherited defect in either the gene MLH1 or the gene MSH2, but other genes can also cause HNPCC. HNPCC is discussed in more detail in our document Colorectal Cancer.

Lifestyle and environmental factors

Risk factors such as a high-fat diet, smoking, sedentary lifestyle, and exposure to cancer-causing substances in the environment have a great impact on a person's risk of developing many types of cancer. Although none of these factors has been definitely found to influence a person's risk of developing adrenal cancer, smoking has been suggested as a risk factor by some researchers.

prevented adrenal cancer 

Since there are no known preventable risk factors for this cancer, it is not now possible to prevent this disease, specifically. Not smoking is a way to lower the risk for many cancers, and perhaps even adrenal cortical cancer.

CAUSES OF CANCER

Causes

The great majority of cancers, some 90–95% of cases, are due to environmental factors. The remaining 5–10% are due to inherited genetics. Environmental, as used by cancer researchers, means any cause that is not inherited genetically, such as lifestyle, economic and behavioral factors, and not merely pollution. Common environmental factors that contribute to cancer death include tobacco (25–30%), diet and obesity (30–35%), infections (15–20%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity, and environmental pollutants.

It is nearly impossible to prove what caused a cancer in any individual, because most cancers have multiple possible causes. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, then there is a small chance that the cancer developed because of air pollution or radiation. Excepting the rare transmissions that occur with pregnancies and only a marginal few organ donors, cancer is generally not a transmissible disease.

Chemicals

Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.Tobacco smoking, for example, causes 90% of lung cancer. It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosaminesand polycyclic aromatic hydrocarbons. Tobacco is responsible for about one in three of all cancer deaths in the developed world, and about one in five worldwide. Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.

In Western Europe, 10% of cancers in males and 3% of all cancers in females are attributed to alcohol exposure, especially cancer of the liver and of the digestive tract. Cancer related to substance exposures at work is believed to represent between 2–20% of all cases. Every year, at least 200,000 people die worldwide from cancer related to their workplaces. Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling tobacco smoke or asbestos fibers on the job, or leukemia from exposure to benzene at their workplaces.

Diet and exercise

Diet, physical inactivity, and obesity are related to up to 30–35% of cancer deaths. In the United States excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of all cancer deaths. Correspondingly, a UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer, and responsible for around 12,000 cases each year in that country. Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system. More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.

Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer. Aflatoxin B1, a frequent food contaminate, causes liver cancer. Betel nut chewing causes oral cancer. The differences in dietary practices may partly explain differences in cancer incidence in different countries. For example,gastric cancer is more common in Japan due to its high-salt diet and colon cancer is more common in the United States. Immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.

Infection

Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion varies in different regions of the world from a high of 25% in Africa to less than 10% in the developed world. Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also have an effect.

A virus that can cause cancer is called an oncovirus. These include human papillomavirus (cervical carcinoma), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma), and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma. Parasitic infections strongly associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).

Radiation

Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.

Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco. Radiation can cause cancer in most parts of the body, in all animals, and at any age. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.

Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.

Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer. However, studies have not found a consistent link between cell phone radiation and cancer risk.

Heredity

The vast majority of cancers are non-hereditary ("sporadic cancers"). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of all cancer. Some of these syndromesinclude: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer, among others.

Physical agents

Some substances cause cancer primarily through their physical, rather than chemical, effects on cells. A prominent example of this is prolonged exposure toasbestos, naturally occurring mineral fibers that are a major cause of mesothelioma, which is a cancer of the serous membrane, usually the serous membrane surrounding the lungs. Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as wollastonite, attapulgite, glass wool, and rock wool, are believed to have similar effects. Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel, and crystalline silica (quartz, cristobalite, and tridymite). Usually, physical carcinogens must get inside the body (such as through inhaling tiny pieces) and require years of exposure to develop cancer.

Physical trauma resulting in cancer is relatively rare. Claims that breaking bones resulted in bone cancer, for example, have never been proven. Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer, or brain cancer. One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. Frequently drinking scalding hot tea may produce esophageal cancer.Generally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of repairing the trauma, rather than the cancer being caused directly by the trauma. However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.

It is controversial whether chronic inflammation can directly cause mutation. It is recognized, however, that inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the microenvironment around tumors. Furthermore, oncogenes are known to build up an inflammatory pro-tumorigenic microenvironment.

Hormones

Some hormones play a role in the development of cancer by promoting cell proliferation. Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.

Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary, and testis, and also of thyroid cancer and bone cancer. For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain why these women have higher risk of breast cancer, even in the absence of a breast-cancer gene. Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry, and have a correspondingly much higher level of prostate cancer. Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.

Other factors are also relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers. Women who takehormone replacement therapy have a higher risk of developing cancers associated with those hormones. On the other hand, people who exercise far more than average have lower levels of these hormones, and lower risk of cancer. Osteosarcoma may be promoted by growth hormones. Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels, and thus discouraging hormone-sensitive cancers.