Cancer: The Deadly Menace First printed in Double Helix Network News, Winter 2002 by C.A. Sharp We waited in our vet’s exam room for Sydney’s x-rays to be developed. He had an abnormal bony lump on his right foreleg, just below the shoulder. Sydney was a rescue who’d been saved from a county pound only to bounce through several homes before finding his “forever home” with us. And now we were facing the possibility that this happy, affectionate little blue merle Australian Shepherd had osteosarcoma, a deadly bone cancer. “Cancer” is one of those frightening words you never want to hear in connection with someone you love, human or animal. Cancer can be disfiguring. It can cause terrible suffering; even the treatments available are often harrowing. Cancer can kill. Anyone who has had to face cancer inevitably asks, “Why?” People wonder what they did wrong to bring this terrible situation upon their loved ones. The truth is that most aspects of cancer development are beyond our control, though there are some things dog owners and breeders can do to reduce the risk, as we will discuss later. Cancer isn’t one disease, but a whole class of diseases in which cells proliferate abnormally and at the expense of the host. Cancer cells multiply at abnormal speed, invade other tissues and are incapable of performing their normal functions. There are several sub-classes of cancers. Carcinomas are cancers of the epithelial tissues, the skin and internal linings of the body; sarcomas affect connective tissue, bones, muscles, cartilage and even blood vessels; leukemias occur in the white blood cells; and lymphomas in the lymph system. Cancer is seen most frequently in elderly dogs, half of whom will be affected. It occurs more often in purebreds than mixes and some types of cancer are more frequent in certain breeds. Cancer is the most common non-accidental cause of death for dogs. Common canine cancers include breast cancer, sarcomas, lymphoma and squamous cell carcinoma, a skin cancer. Mast cell tumors, another type of skin cancer, are the most common. Interestingly, dogs rarely suffer some cancers common to humans, including lung, colon and ovarian cancer, probably due to dogs’ differing physiology and life-style. The canine reproductive system is different in both form and some aspects of function. Dogs have much shorter digestive tracts and different dietary needs and habits, and they don’t live as long. And dogs don’t smoke, though they do live with smokers and exposure to second-hand smoke can be even more dangerous. Some breeds have particular cancer problems: Large and giant breeds are more prone to osteosarcoma, Bernese Mountain Dogs to hystosarcoma, and black Standard Poodles to squamous cell carcinoma, to name a few. Cancers are genetic in origin, though they are not likely to be inherited. However, all cancers are caused by genetic mutations. Most of these do not occur in germ-line, or reproductive, cells. Cancerous mutations are not confined to alterations made to genes. Chromosomes can be damaged as well. Sometimes, for reasons yet unknown, a chromosome will tangle, a condition called “knotty DNA.” If this happens near a tumor suppressor gene, cancer may result. Transpositions, where bits of one chromosome switch places with bits of another, can also lead to cancer. Chronic myelogenous leukemia in humans is an example: A bit of chromosome 22 attaches itself to chromosome 9 forming a “Philadelphia Chromosome” (named for the place of its discovery.) In so doing, it fuses two genes together, leading to proliferation of leukemia cells. More frequently, cancers are caused by copying errors or direct DNA damage caused by things like chemicals or ultraviolet light. It is normal for a dog’s cells to divide, making copies of the chromosomes in the process. This happens many thousands of times from conception to death. No copying system is perfect; the DNA code is subject to occasional misprints, scrambled content and deletions. Over time, mistakes will accumulate. Cancer is more frequent in the elderly because they have undergone far more cell divisions and had longer exposure to environmental conditions that can cause this kind of damage to the DNA. But not all cancers occur in the old. Exposure to radiation or toxic chemicals can cause DNA damage leading to cancer. Some individuals are born with mutations that predispose them to cancer. Wilms’ Tumor is an inherited kidney cancer that occurs in children. Cancers have been linked to viruses, which hijack a cell’s DNA machinery to reproduce themselves. During this process, cells can wind up with viral DNA inserted into their own. Depending on which genes are affected by the insertion, cancer may develop. The cell is not without methods of counteracting these mistakes. There are redundancies in the system designed to render some mutations unimportant, if not eliminate them altogether. For example, there are “housekeeping” genes that form proteins designed to repair or snip out and discard damaged sections of DNA. If sufficient DNA damage has occurred, tumor suppressor genes, such as BRCA1 and p53, induce apoptosis, causing the defective cell to self-destruct. Not surprisingly, many cancers have been linked to mutations in tumor suppressor genes. BRCA1 mutations are very common in human breast cancer. Many cancers in humans and dogs are associated with p53 mutations, including canine mammary cancer. If a mutation occurs in a germline (reproductive) cell, that mutation will be inherited. However, both copies of the tumor suppressor gene must be damaged before it loses its ability to protect the cell. Proto-oncogenes are a type of gene which regulates normal cell growth and division and thereby prevent cells from multiplying wildly. When these genes mutate, they are called oncogenes. Oncogenes can render tumor suppressor genes inactive. They can be dominant or recessive, so a mutation in a single copy may lead to cancer. Another example, of redundancy designed to prevent serious DNA mistakes is written into the DNA code. Within every gene are triplets of base pairs called codons. They are like “words” in the code. They produce bits of RNA necessary to cell function. The bases, adenine, guanine, cytosine and thymine, commonly noted as A, C, G, and T, will only form A-C and G-T pairs. When making RNA, the double-stranded DNA “unzips” and collects complementary bases (though RNA substitutes a uricil for thymine.) The DNA code TAC will form the complementary RNA codon GCA, which ultimately results in a particular particular amino acid being used in at a particular point in a protein. However the DNA codons TAA, TAG and TAT will result in the same amino acid being used. If a copying error occurred that changed TAA to TAT, there would be no effect on cell function. A dog owner or breeder has only a small amount of control over environmental factors that can lead to cancer. The fact that these diseases are a major cause of death among humans shows that we are a long way from being able to control all the risks. But taking the same kind of precautions with your dogs that you do for yourself and your family will help. Provide clean water, minimize exposure to polluted air and, for dogs with unpigmented or lightly-pigmented skin, avoid excess exposure to bright sunlight. Limit unnecessary exposure to chemicals like pesticides. Avoid overuse of beneficial chemicals like medications, parasite controls, and even common home and garden products. A good, balanced diet is important. Research on canine dietary links to cancer has been limited, but the numerous studies citing connections—positive and negative—of certain items or food preparation processes in human cancers indicates this is likely the case with dogs as well. Whether you use a commercially prepared feed or a homemade diet, make sure it contains proper levels of the anti-oxidant vitamins like C and E, and substances like elegiac acid, which studies have show can improve function of the tumor suppressor p53. This won’t guarantee that all of your dogs will be cancer free, but it will help. Some aspects of cancer control are more directly in a breeder’s hands. Because certain breeds of dog and certain families within a breed will have a tendency to develop certain cancers, the breeder should learn which cancers are most likely to occur and note which dogs have had them. With this knowledge and careful mate selection, the breeder can reduce the risk of producing dogs that will develop those cancers. For example, if a dog and bitch each had a grandparent that had osteosarcoma, it would be unwise to breed them to each other Do not breed for traits that may pre-dispose a dog toward cancer, like large areas of unpigmented skin. . Another factor that can contribute to cancer is inbreeding. Purebreds are more cancer-prone than mixes and some breeds have particular cancers more frequently than dogs in general. All breeds are of necessity to some degree inbred; each represents only a segment of the over-all canine gene pool, including both desirable and undesirable genes. Within breeds, there is evidence that dogs with higher coefficients of inbreeding (COI) are more likely to develop cancer at a younger age than those less-inbred individuals within the same breed. It is definitely true that if a cancer-causing mutation is present in germ cells in an individual, inbreeding or linebreeding on that individual will increase risk of producing offspring that inherit two copies of that mutated gene. In view of this, breeders would do well to avoid increasing COI and, where possible, make mating selections that will lower it. On a broader level, it would be extremely useful if breed clubs and breed health organizations would conduct cancer surveys to discover exactly what kinds of cancer are occurring within a breed and at what ages. This knowledge will not only let breeders know what to watch out for but indicate areas of research which the club or group might want to target for funding. The fifteen minute wait for Sydney’s x-rays seemed to last forever. Finally, our vet came in and snapped the films onto the viewer. I had the good news before he could tell me. Sydney did not have cancer. At some time in his past, his leg had been broken, possibly due to being kicked, and he had been left to heal on its own. The bone had mended well but was misshaped. No tumor, no cause for worry—this sad episode from Sydney’s past was long behind him. With heartfelt thanks to our vet, we left his office knowing that our gentle young dog would be with us for many happy, healthy years to come. SPECIAL NOTE: There are now vets around the country who specialize in oncology—the treatment of cancer. I am aware of two such practices and I am sure there are others. For reader reference, the two I am aware of are listed below. – CAS VCA/Coast Pet Clinic 1560 Pacific Coast Hwy. Hermosa Beach, CA (310) 372-8881