Papillary Thyroid Cancer: An Inquiring Patient's Guide

Q.  How did I get this cancer?

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GENERAL DISCLAIMER
This site is designed for informative purposes only and is not engaged in rendering medical advice or professional services. The author has no medical training. The information provided through this site should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, you should consult your health care provider.
© Julia Lawrence 1999

At a basic level, your thyroid cancer was caused by genetic changes

Cancer is not an external disease, like bacterial infections. Cancer cells are our own cells, but they are behaving in ways they are not supposed to. Our body's cells do not usually over-multiply. When we have enough of a particular type of cell, our bodies remain stable by balancing the birth of new cells with the death of old cells. However, cancer cells continue to multiply instead of dying, and thus grow to the point where they can endanger other parts of our body. Moreover, sometimes our body's cells of one type (say thyroid cells) lose the inhibition against growing outside the tissue where they belong. Normally, a thyroid cell stranded outside the thyroid would die naturally. However, when this "suppression" is lost, cells can grow elsewhere, and this is what happens with secondary tumours, also known as "metastases". A metastasis is a group of cancer cells growing outside the original tissue - for example, thyroid cells growing outside the thyroid, perhaps in lymph nodes, the lungs, or the bones.

Cells get their instructions about life and death from their own nuclear genetic code, and from the activity of other "signals" released by other cells which ultimately have a genetic origin. If the genetic code changes, the cell may begin to misbehave. However, only certain genetic changes will lead to cancer. In a normal human's lifetime, every gene in their genetic code is likely to have undergone about 10 billion mutations somewhere in the body (Alberts). Since only one third of us get any kind of cancer during our lifetimes, you can see how rare it is to get the "right" mutation at the "right" time and place for cancer to develop.

In some instances, there may be little chance involved - a few people may inherit genes from their parents which predispose them to papillary thyroid carcinoma. Although any gene(s) responsible for "familial papillary carcinoma" are not yet known, there has been enough research documenting families with a high prevalence of papillary carcinoma to think that heredity of such genes is a possibility (Schneider).

However, the ten billion figure mentioned earlier relates to normal, "spontaneous" changes that occur in the individual, not their parents. And yes, in a large population, some cancers should occur "spontaneously" - utterly by the rules of chance. Your thyroid cancer could have arisen spontaneously. However, sometimes we are exposed to higher risk of a cancer-causing mutation, and the factors that increase this risk are called carcinogens. It is these carcinogens that researchers are seeking as "causes", and that are thought to be responsible for many cases of cancer in human beings.

The only proven cause of thyroid cancer is radiation during childhood

Since a link was first reported between childhood radiation and thyroid cancer in 1950, many studies have gone on to demonstrate this link. The most recent have involved the nuclear accident at Chernobyl, but other studies have looked at nuclear fallout, as well as various types of radiation treatment for benign diseases. These studies have pointed to childhood as the time during which radiation exposure is likely to cause thyroid cancer, perhaps because children's thyroids are still growing and therefore have more chance of developing the necessary genetic changes. A recent study in the aftermath of Chernobyl suggests that those most at risk of thyroid cancer from radiation are children under five years old (Tronko 1999).

The key points to understand about radiation as a "cause" are these:

  • radiation doesn't cause cancer in everyone who gets the same dose - in fact it only brings on cancer in a minority of those affected
  • most radiation sources are not sufficiently powerful to increase your risk of cancer

Radiation poses no risk below about 100 rads, and the risk increases above that until it reaches 1500 rads

How much radiation would you need to give you an increased chance of thyroid cancer? Statistically, you will have an increased risk for thyroid cancer if you have been exposed to radiation between 100 and 1500 rads sometime before you reach adulthood (Collins). Key points:

  • It is not sufficient to get this over a long period - we all receive about 100-200 rads of radiation per year from the background (Boice).
  • X-rays for diagnosis (like chest x-rays) are not strong enough to increase your risk
    • a medical X-ray would typically deliver about 25 rads
    • 25 rads is not enough to give you a greater chance of thyroid cancer than your non-x-rayed neighbor
  • Several doses of X-rays over a short period of time, for the purpose of treatment rather than diagnosis, could result in an increased risk of thyroid cancer, if the total dose is at least 100 rads
    • they key is that they are delivered over a short period of time
    • example: in 2872 children treated for an enlarged thymus, using doses averaging 119 rads, 24 developed thyroid cancer over the following 40 years (Collins)

The risk of thyroid cancer from radiation exposure has been estimated at up to 4 cases per million women exposed per rad (a measure of radiation) of exposure per year, and 1 case per million men exposed per rad of exposure per year (Collins). In other words, if 1000 children (half girls and half boys) were treated with 300 rads of radiation for some benign disease, on average you would expect that, over a 40 year period, 24 girls and 6 boys would develop thyroid cancer. Here is the equation:

300 rads x 40 years x 4 cases per rad per year (per million patients) = 48,000 cases per million patients, which is the same as 24 out of 500 girls
300 rads x 40 years x 1 case per rad per year (per million patients) = 12,000 cases per million patients, which is the same as 6 out of 500 boys

The reason radiation doesn't cause cancer in everyone, even if it is strong enough to increase you risk of cancer, is that radiation is only an indirect cause in the first place. Remember, you need genetic change to bring on cancer. Radiation can bring on genetic change, if the radiation dose is within the right range. Below a that range, radiation is weak, and will induce very little genetic change. The fewer genetic changes you have, the less your chance of getting one of the very few changes that can lead to papillary thyroid cancer. Naturally, as the radiation dose increases, your chance of getting one of those changes increases. But at really high levels of radiation the dose kills the cells, leaving them no chance to get the relevant change and multiply. That means they aren't around to become cancerous.

If you would like to know whether your case of papillary thyroid cancer could be linked to childhood radiation, you should find out what sources of radiation you were exposed to, particularly fallout, nuclear spills, and medical treatments. You should then find out from relevant authorities (your doctors for treatments, the government for fallout and nuclear spills) how much radiation you could have been exposed to, and over what period of time. If you were indeed exposed to 100 rads or more over a short period of time - say an afternoon of "fun" watching one of the atomic bomb blasts in the Midwest from downwind, and then living in the area of heaviest fallout - then you have as good an indication as you are likely to get of the probable cause of your thyroid cancer.

For most patients, the cause of thyroid cancer cannot yet be pinned down

You may never know what caused your cancer. Most patients are unable to find a radiation event during their childhood that could clearly be responsible for their thyroid cancer. Some of these people may have a case of "spontaneous" mutations resulting in cancer, i.e. bad luck. Others may have been exposed to factors that increase risk, but which research has not yet linked to thyroid cancer.

Many other factors have been investigated, but none show a conclusive link to thyroid cancer. The following table (from Collins), lists some factors that people have studied in the search for other causes of thyroid cancer. Of these factors, some may contribute, others may not, but none of these factors is a proven cause of thyroid cancer.

Factors studied in thyroid cancer - not proven causes. (from Collins)

Dietary iodine, goitrogens, Hashimoto's thyroiditis, Graves' disease, goiter, age, sex, ethnicity, previous breast cancer, Gardner's syndrome, partial thyroidectomy, tonsillectomy, allergy and skin conditions, parathyroid benign tumour, alcohol consumption, dietary calcium and vitamin D, phenobarbital, diphenoxylate, griseofulvin, bisacodyl, senna, spironolactone, obesity, having given birth to more than one child, oral contraceptives, lactation suppressants, estrogens.

As you can see, the various unproven factors implicate more or less every individual on the planet. None are proven causes of thyroid cancer in any case. With the current state of research, you are unlikely to find the cause of your cancer outside of radiation, and unlikely to dramatically widen the field of possibilities by adding to the above list. Instead, future additions to the real causes of thyroid cancer, in my personal opinion, will probably come from a better understanding of how thyroid cancer operates at the genetic and molecular level.

A potential source of new explanations for thyroid cancer is genetic research

The typically slow growth of thyroid cancer makes it difficult to pin down causes. Based on research into thyroid cancer resulting from radiation, research suggests that this cancer usually does not develop until 10-20 years after exposure (Collins). If that is also true of any other causes of thyroid cancer, it will make identifying those causes, not to mention studying them, very difficult.

However, many children in Belarus, Ukraine, and Russia were diagnosed with thyroid cancer beginning about four years after the Chernobyl nuclear power plant disaster. There are also anecdotal cases of individuals whose cancer was monitored for a time prior to treatment (e.g. pregnant woment), and in whom the cancer grew rapidly. This suggests that under special circumstances, thyroid cancer can develop rapidly. Research into such cases may ultimately help us better understand what causes papillary cancer at the cellular and genetic level. That understanding should in turn help future researchers make intelligent hypotheses about practical causes of thyroid cancer, as well as variations in its behaviour - such as speed of growth, whether it metastasizes, and so on. Understanding the genetic route to these cases will give researchers a starting point for the genetic route to other cases of thyroid cancer.

Already some genetic factors have been identified. Most interesting is an "oncogene" called PTC/ret, which is found only in papillary thyroid cancer cells, and not in any other types of thyroid cancer, nor in normal thyroid cells. An "oncogene" is a "dominant" mutation of a gene which stimulates the cells to proliferate or spread beyond its original location. Our genes all come in pairs - twins as it were - and in terms of causing cancer, the "dominant" nature of oncogenes means that it is enough for only one of the pair to mutate - you don't need both in order to get cancer.

The PTC/ret oncogene does not occur in every case of papillary thyroid cancer. However, one version of it, PTC/ret3, has been found in a very high proportion of some groups with fast growing, aggressive disease, such as children with the disease in post-Chernobyl Belarus (Smida). Another version, PTC/ret1, seems to be more common in slower-growing papillary thyroid carcinomas (Smida).

Several other "oncogenes" have been identified in some cases of papillary thyroid cancer, and it may be that the specific behavour of a given patient's cancer depends on a sort of "cocktail" of the particular genetic mutations they have. Again, in the case of PTC/ret there is evidence that this gene is sufficient to generate papillary thyroid cancer "in one genetic step" (Fischer). That could explain why some cases seem to have such a short "latency" period (delay from cause to diagnosability) - this genetic change doesn't have to wait for another change in order to bring about papillary thyroid cancer. An understanding of how different genetic "recipes" for papillary thyroid cancer result in different behaviour of the disease may yet come, as researchers get a better grip on all the many possible genetic development paths of this disease.

There are many mysteries about papillary thyroid cancer which may be resolved by a better understanding of thyroid cancer genetics. For example:

  • given how rarely this disease is given as a diagnosis, why do around 10% of all autopsies show undiagnosed "microcarcinoma" - i.e. thyroid cancer which is too small to be detected in a living person?
  • why is this disease so much more common in women than in men?
This and much else should become clearer over the coming years. By the end of the next century, our descendents may think it laughable that so many of us worried so much over how we had developed our cancers when, to them, the answers will be completely obvious. If we are particularly wise as a species, that understanding may even lead to good prevention, and thus to fewer cases of the disease.

Sources:

  • Alberts et al, Molecular Biology of the Cell. 3rd ed, 1994.
  • Boice, "Risk factors: ionizing radiation". From the National Cancer Institute Web Site.
  • Collins, "Thyroid Cancer: controversies and etiopathogenesis." In Falk (ed), Thyroid disease: endocrinology, surgery, nuclear medicine, and radiotherapy, 2nd ed, 1997.
  • Schneider, "Pathogenesis", in Werner and Ingbar's The Thyroid, 7th ed, 1996.
  • Smida et al, "Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus." Int J. Cancer, 5 Jan 1999, volume 80, no. 1, pp. 32-8.
  • Tronk et al, "Thyroid carcinoma in children and adolescents in Ukraine after the Chernobyl nuclear accident: statistical data and clinicomorphologic characteristics", Cancer 1999 Jul 1; vol. 86, no. 1, pp. 149-56.

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Contact the author of this site at julia_lawrence@papthyca.com.

Last updated on 30 August 1999.