Genes, Wolfhounds and Cancer

Cancer is a genetic disease. This does not mean that cancer is a hereditary disease—sometimes it is, but more often, it is not. It is always a disease of genes “run amok,” and it always has its beginnings inside one of the body’s trillions of cells. Just one mistake in the chemical ‘spelling’ which makes up one gene can lead to a series of events that ends, tragically, as a malignancy. Just how this occurs in our hounds is the subject of this article.

Each cell in the wolfhound’s body (or your own, for that matter) has a specific job to perform. Kidney cells regulate fluid balance while removing waste products, lung cells exchange oxygen for carbon dioxide, etc. Each cell performs its duty for the good of the whole body, much as a violinist and a clarinetist play different parts in an orchestral performance of, as an example, Beethoven’s Fifth Symphony.

Cells must also maintain the ability to grow. This allows the body to respond to injury by healing, and enables the embryo to grow into an adult. Most of the time, however, cells should not grow. Their ability to divide and reproduce must be kept strictly in check. Going back to the analogy of the violinist and clarinetist, each may be capable of memorable solo performances, but usually the orchestra has a greater need for musicians who use their abilities to contribute to the group effort.

Just as the orchestra’s musicians must be mindful of cues from the conductor while retaining awareness of the orchestra as a whole—how else will they know just how loud that second “Da da da DUM” should be if they haven’t heard the first one?—so cells must respond to signals from each other as well as from hormones, the brain, etc. They are constantly sending and receiving messages letting them know just what’s going on, and what they need to be doing at any given time. And just as each member of the orchestra has the complete score in front of him and knows how his part fits into the whole, so each cell has a complete set of the 38 pairs of chromosomes which, taken together, identify him—or her—as one uniquely individual Irish Wolfhound.

At the same time that each cell is just one very small part of the whole animal, it is a very complex, industrious world in its own right. It teems with proteins and enzymes, each molecule a cog in the machinery of the cell, which is, in turn, a cog in the smooth working of the machinery of the IW body. In fact, there is an unfathomable amount of activity going on every minute of every day in each cell, all of it necessary to sustain life. In every sense, there is more going on than meets the eye...even when that eye is looking through a high-powered microscope.

We tend to think of genes mainly in terms of affecting physical characteristics like coat color, angulation, and tail set. They certainly do that, but they do so much more. They are involved in controlling every aspect of each cell’s existence—they are the ultimate micro-managers. They have the last word in deciding which cells live and which cells are no longer useful to the body and should be removed. There are several genes whose only job is to ensure that these operations are carried out smoothly. There are genes to tell cells to divide when they need to, genes to repair any DNA damage which may occur, and genes to tell cells when it’s time to give up their lives for the greater good of the body.

As it turns out, cells do need to be replaced frequently. Genes designed to facilitate cell replacement are called proto-oncogenes, and they stimulate cellular growth. When the DNA in cells sustains injury, as it does each day, there are genes whose only assignment is to patch them up: these are called DNA repair genes. And finally, when cells have outlived their usefulness, there are genes that police the cells, ensuring that those cells needing to ‘commit suicide’ for the good of the whole body do just that. These are the tumor-suppressor genes, and their role is arguably the most important one of all.

Tumors begin when a cell’s DNA is damaged (mutated), but—and this is a critical distinction—tumors become malignant and can spread only when there is an accumulation of many mutations in a specific set of cells: proto-oncogenes, DNA repair genes, and tumor suppressor genes.

Even when we speak of cancer as being “inherited,” what we really mean is that the predisposition to cancer is inherited in the germline—the complete set of 38 pairs of chromosomes inherited at the time of conception, one set coming from each parent. This is the individual wolfhound’s ‘genome,’ and it contains the DNA which will be present in every single cell (except red blood cells, which do not contain genes).

In humans, we are aware of a few cancers which are caused by inherited defects in genes, such as the BRCA-1 and BRCA-2 genes. These are tumor-suppressor genes impilicated in some types of breast and ovarian cancers. In dogs, malignant histiocytosis in Bernese Mountain Dogs is an example of a cancer believed to have a hereditary basis. But even in these cases, mutations must occur in additional genes for the malignancy to form and be able to spread—to become a cancer.

There will be literally trillions of cell divisions occurring in each wolfhound’s lifetime; there will also certainly be innumerable opportunities for genetic mistakes to accumulate. This is why the risk of cancer increases in dogs as they age, just as it does for us. We know that, of all the malignancies which can occur in dogs, osteosarcoma is the one which occurs most often in wolfhounds and other large and giant breeds. Its incidence increases dramatically as the wolfhound ages. Unfortunately, by the time the IW is limping and we notice a small swelling, a tumor suppressor gene has probably mutated, and the malignancy may have begun to infiltrate surrounding tissue. A few cancer cells may have broken away and begun to circulate throughout the body, using the bloodstream to travel to the lungs and other long bones. In humans, the process which begins as a single, undetected mutation in one gene and ends up as an actual malignant cancer usually takes many years. In dogs, the process of successive mutations seems to be accelerated, making cancer even more difficult to detect in its earliest stages, when we might have a better chance of managing it.

There are many reasons why searching for specific genes involved in IW diseases is important. The genetic language “spoken” in hounds and humans is identical, and canine research may have human applications. Researchers have begun to realize the wealth of information contained within a purebred’s pedigree, and this information is particularly powerful when combined with the detailed phenotypic data we’re compiling in the Lifetime Cardiac Study. We hope, and we believe, that one day, we may be able to rely on non-invasive genetic testing to breed away from these diseases without needlessly eliminating dogs who may not carry a particular defect from our already small gene pool. We must start somewhere, and that’s why the IWF is dedicated to collecting and storing our hounds’ blood in our own DNA Bank. Each blood sample can be used for multiple studies which will benefit our breed.

Surely we live in one of the most exciting eras in history. As the secrets contained within genes are revealed, we are presented with unique opportunities to use this knowledge for the betterment of our beloved breed. What could be better than using what we learn to help our hounds?

Maestro, cue the orchestra!