Causes and Risk Factors of Thyroid Cancer

It's unclear what exactly causes most thyroid cancer, though some cases are linked to inherited conditions. There are certain risk factors for thyroid cancer, including exposure to radiation, having a diet that's low in iodine, and being female. The four main types of thyroid cancer are papillary, follicular, medullary, and anaplastic. Less common thyroid cancers include thyroid lymphomas, sarcomas, and other rare tumors.

Common Causes

Thyroid cancer occurs when the DNA in your thyroid cells mutates (changes), causing the cells to multiply in an uncontrolled manner and invade locally. As these abnormal cells accumulate, they form a tumor that can then spread to other parts of the body.

There are a number of genes that, during the course of your lifetime, can develop mutations associated with thyroid cancer, including:

• RET gene: Medullary thyroid cancer can be caused by point mutations found in different parts of the RET gene. Some medullary thyroid cancers are inherited as part of a hereditary cancer syndrome or as part of familial medullary thyroid carcinoma syndrome (see below). In cases of medullary thyroid cancer that aren't inherited, the mutations are usually only found in the cancerous cells. Chromosomal breaks can occur within the RET gene resulting in fusion genes between fragments of the RET gene and fragments of other genes. This type of genetic rearrangement occurs in approximately 20% of papillary thyroid cancer (PTC); the fusion oncoproteins generated are called RET/PTC proteins. The RET/PTC fusion proteins are found more commonly in children exposed to external radiation but not in adults exposed to radiation.
• BRAF gene: Thyroid cancer cells with BRAF gene mutations tend to grow and spread more rapidly than cancer cells with RET mutations. These mutations are less common in children and those who have had radiation exposure. It's extremely rare to have changes in both the RET and BRAF genes.
• NTRK1 and MET genes: Mutations in these genes have also been associated with papillary thyroid cancer.
• RAS oncogene: Changes in the RAS oncogene are found in some follicular thyroid cancers, as is PAX8/PPAR-γ rearrangement.
• TP53 gene: Changes in this gene, which gives instructions for making a protein that suppresses tumors, are associated with anaplastic thyroid cancer.
• CTNNB1 oncogene: Mutations in this gene may also be rarely associated with anaplastic thyroid cancer.

Genetics

Most people who are diagnosed with thyroid cancer don't have a genetic component or a family history, but there are some inherited conditions that are linked to thyroid cancer.

Familial Medullary Thyroid Carcinoma (FMTC)

Around two out of 10 cases of medullary thyroid cancer are due to inheriting a mutated gene. When this occurs, it's known as familial medullary thyroid carcinoma (FMTC). In these cases, the thyroid cancer can appear by itself or it may occur along with other tumors.

When FMTC occurs with other tumors, this is known as multiple endocrine neoplasia type 2 (MEN 2).

Both FMTC and MEN 2 are inherited and are caused by mutations in the RET gene. We all inherit two copies of each gene, one from each parent. If you have a RET mutation, this typically means that one copy of the RET gene you inherit is mutated. With either FMTC or MEN 2, cancer typically develops in childhood or young adulthood.

Other Thyroid Cancers

Your risk of developing other, more common forms of thyroid cancer is higher if you have any of these genetic conditions:

• Familial adenomatous polyposis (FAP): This condition, which is caused by defects in the APC gene, causes colon polyps and creates a high risk for colon cancer. It also raises the risk for other cancers, including papillary thyroid cancer.
• Cowden disease: This condition, which is typically caused by mutations in the PTEN gene, leads to increased thyroid problems, benign growths, and a higher risk of developing papillary or follicular thyroid cancers, as well as uterine and breast cancer.
• Carney complex, type I: Caused by defects in the PRKAR1A gene, this condition also causes benign tumors and a higher risk of developing papillary or follicular thyroid cancers.
• Familial nonmedullary thyroid carcinoma: Though the genetic component is not understood, having a first-degree relative who has had thyroid cancer (parent, sibling, or child) increases your risk of thyroid cancer as well. Papillary thyroid cancer, in particular, often runs in families and may be caused by genes on chromosomes 1 and 19.

Risk Factors

There are several risk factors for developing thyroid cancer:

Sex and Age

Thyroid cancer is more common in women than in men.

Women who are diagnosed with thyroid cancer are typically in their 40s or 50s and men are usually in their 60s or 70s.

Low Iodine Levels

In places where people get less iodine in their diet, follicular thyroid cancer is more prevalent. If your diet is low in iodine and you've been exposed to radiation, your risk of developing papillary thyroid cancer may also be increased as well. In the United States, most people get enough iodine through iodized table salt and other foods they consume.

Radiation Exposure

Being exposed to high levels of radiation such as those found in certain diagnostic tests and treatments and due to nuclear fallout increases the risk of thyroid cancer. The latter may sound like a far-fetched concern, but certain areas of the United States experienced radioactive fallout after weapons testing done in the 1950s, and such weapons do still exist today. This exposure can also occur due to accidents at power plants.

The amount of radiation exposure and the age at which you're exposed are important. The larger the amount of exposure and the younger you are, the higher your risk.

Radiation treatments: Children and teens who receive high doses of radiation to treat cancer such as lymphoma have a higher risk of developing other cancers, including thyroid cancer, later.

Diagnostic X-rays: Exposure to diagnostic radiation is associated with an increased risk for thyroid cancer, especially with multiple exposures. Your thyroid gland is very sensitive to radiation, and radiation exposure, especially at a young age, is a proven and well-known risk factor for thyroid cancer. One common source of exposure to this type of radiation in the United States is X-rays done for medical diagnosis, especially dental X-rays and computed tomography (CT) scans.

One way to protect yourself is to ask your dental care professional to give you a lead thyroid collar when doing any dental X-rays, which the American Dental Association recommends anyway. Despite these recommendations, some dentists do not have thyroid collars or lead aprons that have a neck shield. In that case, though not ideal, you can use a collarless lead apron they have on hand for pregnant patients to shield your neck area.

If you have children, it's especially important to minimize their exposure to any routine or unnecessary dental X-rays and insist that their dentists and orthodontists also use a thyroid collar. Orthodontia in particularly can be a source of numerous dental X-rays.

Nuclear accidents: In March of 2011, an accident at the Fukushima Daiichi Nuclear Power Plant in Fukushima, Japan—which was caused by a post-earthquake tsunami that hit the plant—triggered a release of radiation and exposure to radioactive materials in the country and in areas downwind of the nuclear plant.

Nuclear plant accidents such as this one and the 1986 Chernobyl accident in Russia result in the release of radioactive iodine-131. Exposure to radioactive iodine-131 is a known risk factor for thyroid cancer, and the risks are greatest if the exposure occurs in infants, children, and adolescents.

A large spike in infant to adolescent thyroid cancer rates was seen starting around five years after the Chernobyl accident. The incidence was highest in areas such as Belarus, which was in the path of Chernobyl’s nuclear fallout, but whose population was unprotected by potassium iodide treatment. Some areas downwind of Chernobyl, such as Poland, received preventive potassium iodide tablets, which protect the thyroid from absorbing radioactive iodine if taken in the hours before and after the exposure.

Given the Chernobyl experience and widespread public concern in Japan, the Fukushima Health Management Survey was launched in July of 2011 to evaluate the risks of radiation exposure on the population. The survey involved large-scale thyroid ultrasound screening of the population around Fukushima in an attempt to detect potential thyroid cancer.

According to researchers, however, while there is an increased incidence of thyroid cancer in Fukushima, it's much smaller than the significant increase that occurred after Chernobyl. This has led researchers to conclude that the amount of exposure in Fukushima residents was much lower than that of the Chernobyl accident and that evidence of this radiation exposure causing thyroid cancer isn't strong.

While Japanese researchers have not established any significant increase in thyroid cancer rates attributable directly to the Fukushima nuclear accident, they also indicate that more research is needed to explore the situation further. In the end, further epidemiological studies will help to determine whether the exposure to radioactive iodine-131 after Fukushima was of a level sufficient enough to cause a demonstrable increase in thyroid cancer—such as occurred after Chernobyl—or if the increase is merely a byproduct of more rigorous, widespread, and sensitive thyroid cancer screening.

Associations

There have been some studies on the associations of certain factors that are linked to thyroid cancer. Keep in mind that an association is not the same thing as a cause; it simply shows a link that more than likely needs further study.

Power Plant Emissions

The Indian Point nuclear reactor is located in Buchanan, New York, about 23 miles north of New York City. When the plant opened in the mid-1970s, the rate of thyroid cancer in four surrounding counties—Westchester, Rockland, Orange, and Putnam counties—was 22% below the U.S. rate. Now, thyroid cancer cases have jumped from around 50 per year to more than 400 per year in the region, with a rate that is 53% above the national average. 

A peer-reviewed study conducted by the Radiation and Public Health Project used data from the New York State Cancer Registry to track rates of cancer in these four counties over four decades. The findings suggest that overall increases in cancer and soaring thyroid cancer rates may be the result of emissions from the Indian Point nuclear power plant.

The researchers compared cancer rates for five-year periods between of 1988 and 2007. They found unexplained increases in 19 out of 20 major types of cancer, with the greatest increase in thyroid cancer. According to the researchers, the report’s findings are consistent and statistically significant, and suggest that one or more factors—potentially radiation exposure from Indian Point—are causing otherwise unexplained increases in cancer rates in the region.

Given this understanding of the relationship between radiation and thyroid cancer, the study calls for more comprehensive research into thyroid cancer patterns and the relationship to nuclear plants in an attempt to explain soaring rates. Whether Indian Point is a health risk has wide implications for the almost 2 million people who live within 20 miles, and the more than 17 million people who live within a 50-mile radius of the plant, a larger population than surrounds any other U.S. nuclear plant.

Parvovirus B19

Researchers have been looking at the role of human parvovirus B19 in thyroid cancers and other disorders. What they've found is that there is a strong link between papillary thyroid cancer and B19. Parvovirus B19 is a virus that most often causes an illness known as fifth disease. The viral illness is most common in younger children and causes a rash on the cheeks, arms, and legs.

B19 has been found in the majority of the tumors studied, showing that the thyroid is highly capable of harboring it. Researchers believe that their findings suggest that B19 is infecting the thyroid gland prior to the formation of tumors. Again, more research needs to be done on this association.

Hysterectomy

One large study of women who had a hysterectomy showed that they had a significantly higher risk of developing thyroid cancer than women who had not had a hysterectomy. The researchers concluded that more research needs to be done to clarify the potentially similar risk factors for thyroid cancer and the need for a hysterectomy. Keep in mind that even if the risk is increased, it's very possible that only small numbers of women actually develop thyroid cancer after hysterectomy.

Thyroxine

You may have heard that taking synthetic thyroxine, called Synthroid (levothyroxine), for low levels of thyroid hormones found in hypothyroidism can lead to thyroid cancer. While one study found there is an association between regularly using thyroxine and later developing thyroid cancer, this is the first study to show such an association and it was done on a small sample of people. The authors themselves acknowledge that more research needs to be done on larger populations to validate the findings of this research.

The bottom line is that one study that shows a very small association between levothyroxine use and thyroid cancer is no reason to stop taking Synthroid if that's what your healthcare provider has prescribed. If you do have concerns, be sure to talk with your practitioner about them.